Archive for the ‘Gene Therapy Research’ Category

October 25, 2019

Researchers working to find a cure for malignant mesothelioma are acutely aware of the need for speed: the disease is always considered fatal, and more people are diagnosed with and die of the condition every day. Still, there is a process that must be followed: theories need to be tested in the laboratory before people, and this slows everything down. Recently, researchers at the University of Pennsylvania had the opportunity to see the human results of a protocol that had shown promise with lab animals but is not yet ready for patient testing. They reported a significant positive outcome.

Previous animal research had combined radiotherapy with immune-gene therapy in the treatment of mice with malignant pleural mesothelioma, and had revealed both disease regression and what is called an abscopal effect the combination not only affected tumors that were targeted by radiation but also those that were outside of the range of the therapy.

The researchers from thePerelman School of Medicine at the University of Pennsylvaniadid not intend to test the effect on humans, but ended up doing so with a 67-year-old male patient with malignant pleural mesothelioma who signed on for a clinical trial of immuno-gene therapy. Though his tumor responded positively he needed to stop the treatment due to complications from his tumor for which he was given palliative radiation therapy followed by a standard course of chemotherapy.

Two months after having completed the course of palliative radiotherapy, the man had a CT scan of his chest that revealed that the targeted mesothelioma tumor had shrunk. Remarkably, the treatment had also shrunk tumors that were outside of the irradiated field. This is the first report of a patient having an abscopal effect following radiotherapy and immune-gene therapy. Writing of his results, lead researcher Andrew R. Barsky said, The patients response to immuno-gene therapy, palliative radiotherapy and subsequent chemotherapy, both in-field and out-of-field, was dramatic, and notably more pronounced than what is generally achievable for even well-responding malignant pleural mesothelioma patients In fact, his exaggerated response was far greater than would be expected based upon the volume of disease irradiated and radiation dose employed. The researchers plan to pursue further study of this dynamic.

If you or someone you love has been diagnosed with malignant mesothelioma, positive outcomes like these offer reason for hope. For more information on treatment protocols available to you, contact the Patient Advocates at Mesothelioma.net at1-800-692-8608.

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Oncology Team Reports Promising Results From Combining Immuno-gene Therapy and Radiotherapy - Mesothelioma.net Blog

Let's play a game of word association. I'll go first.

Cell Therapy

What words spring to mind? CRISPR? Medicine? Genetic disorders? Cancer? Gene therapy?

What about green tea? Unlikely, I imagine.

But in a new study published today in Science Advances, researchers from East China Normal University have created an elegant system for activating genetically edited cells using green tea.1Realizing the promise of cell therapiesEngineered cell therapies, deemed the "next frontier" in modern medicine, contain specific cellular material that triggers a desired effect in vitro or in vivo. Such therapies are in development in laboratories across the globe for an array of different conditions, including acute myocardial infarction (heart attack), brain cancer, breast cancer, diabetes and liver diseases. They offer a novel avenue of therapeutics for patients suffering from diseases for which treatment options are limited.For their efficacious and safe use in the clinic, scientists need to be able to regulate the activity of these cells in vivo. Essentially, they require a "remote control". This has proven a major barrier for the delivery of cell therapies to patients. Initial work in this field has adopted antibiotics such as doxycycline or tetracycline as remote-control triggers for gene expression in the cells. However, regular use of antibiotics may result in antibiotic resistance and other adverse side effects.So, what alternatives exist?Haifeng Ye, Professor at East China Normal University, says "Ideal trigger molecules for clinical biomedical applications would be natural, non-toxic, highly soluble, inexpensive, and perhaps even beneficial to health."Previous studies have reported that remote control switches can be activated through the use of food or cosmetic preservatives, vanillic acid, benzoate and phloretin for example. These molecules do not naturally occur in food however, and the safety implications of their long-term use is not well known.A green solution?Nothing beats a good cup of tea. It is the second most popular beverage on the planet (following water) and can be found in the household cupboards of 80% of Americans. Tea is available in a variety of forms, including but not limited to black tea, oolong tea, white tea and green tea. A plethora of research studies have documented the numerous health benefits of green tea consumption, including anticarcinogenic, anti-inflammatory, antimicrobial, and antioxidant effects.The components of green tea most heavily researched with regards to health are the polyphenols, of which the most pertinent are flavonoids, and the most pertinent flavonoids are the catechins.2Post green-tea consumption, the tea catechins and phenolic acids undergo metabolic processing to form the antioxidant protocatechuic acid (PCA). In their latest study, Ye and team have utilized this antioxidant as a "remote control" for activating gene switches in cells. "PCA is a major tea catechin compound produced by humans following green tea consumption that has powerful antioxidant activity. Therefore, in this study, we showed the use of protocatechuic acid (we call it PCA), a metabolite after tea drinking, as a trigger molecule," Ye told Technology Networks.PCA-inducible gene switchesIn the study, the scientists engineered PCA-inducible gene switches in mammalian cells. Initially, they explored the potential for using PCA to monitor cell-based long-term therapies in vivo by integrating the genetic switch into HEK-293 cells and found that the cell line demonstrated reversible and tunable induction kinetics, which the authors regard as "excellent switching performance". This was characterized by negligible basal expression and nonsaturating increases in the transgene output over the course of a 15-day trial.Next, they microencapsulated and implanted the HEK cells into mice. Ye tells us, "The alginate-poly (L-lysine)-alginate-based encapsulation technology was used in our study for cell therapy. This clinically validated implant technology enables the free diffusion of metabolites, nutrients and proteins of lower molecular weights (<72 kDa) across the biocompatible capsule membrane while shielding their cellular content from physical contact with the hosts immune system. The implant technology has been successfully validated in human clinical trials and the performance of the material is continuously improved for clinical applications."The researchers found that, regardless of delivery method (intraperitoneal, oral intake from water, or oral intake from concentrated green tea), PCA could control the secretion of a reporter protein, SEAP, in a dose-dependent manner.Making CRISPR more crisp?CRISPR gene-editing shows promise in revolutionizing personalized medicine. A notable key issue with CRISPR, however, is the "off target" effects that limit its specificity. In this study, the scientists used the PCA-responsive cells to perform more targeted CRISPR gene editing: "By applying newly-designed fusion-protein-based PCA-controlled gene switches to Pol III promoters, we created trigger-inducible expression systems for gRNAs to program PCA-mediated CRISPR/Cas9-activity," says Ye.Exploring diabetes treatment with PCA-induced cell therapyYe and colleagues next tested the potential of the PCA remote control system for treating experimental diabetes using a mouse model. Using the switch, they engineered two different cell lines: one that enabled PCA-inducible expression of the reporter protein SEAP and insulin, and the other producing a short variant of human glucagon-like peptide 1 and SEAP. Implantation of these cells into mouse models of type 1 diabetes and type 2 diabetes mellitus resulted in restored homeostatic fasting blood glucose concentrations and glucose tolerance upon PCA injection.Recognizing that the translation of research findings from mouse models to humans in the clinic can be problematic, the scientists then decided to explore the PCA remote control switch efficacy in non-human primate models of diabetes. In parallel to the treatment efficacy observed in the type 2 diabetic mice, daily oral administration of PCA rapidly increased the expression of glucagon-like peptide 1 and restored glucose homeostasis in diabetic monkeys.In terms of safety, blood biochemical analyses related to inflammatory responses found that white blood cell count, lymphocytes, monocytes, eosinophils, and basophils, did not increase at any point during the treatment when compared with pre-treatment.The study findings certainly excite the authors, "Although there have not yet been preclinical studies for the application of engineered cellbased therapies in humans, this first-in-monkey study demonstrates the feasibility of safely and successfully scaling up a treatment strategy by controlling microencapsulated engineered cells to release therapeutic outputs from animals such as mice to larger NHPs. Therefore, this study substantiates the medical utility of concepts developed in synthetic biology," they note in the discussion of the paper.How much tea is too much tea?Hypothetically, if this therapy was to reach the clinic, I ponder over the possibility of an individual consuming "too much" green tea, and how this might impact the therapy. Ye is quick to inform me that this would not be an issue, "Only custom prepared concentrated green tea can activated the implanted designer cells. The normal green tea drinks cannot activate the implanted cells because of low concentration," he says.The future looks greenThe study is comprehensive, assessing the PCA "switch" in a variety of cell lines and mammalian models with a variety of control measures in place.Thus, in which direction will this research go next? I ask Ye, who tells me, " We will next focus on solving the following limitations:(1) The PCAON-switch was stably integrated into [the] genome by a "Sleeping Beauty" transposon system. Due to a random integration, unwanted insertional mutagenesis might occur. We will next consider using gene editing tools, such as CRISPR, to enable facile and permanent integration of the switch into the targeted genomic sequences in human cells without insertional mutagenesis;(2) The chassis of the HEK-293 cells are easily handled, transfected, and compatible to the PCAON-switch. For translational applications, they must also be safe (no side effects) in humans. Hence, we will test the therapeutic efficiency of the PCAON-switch in autologous parental cells from patients own mesenchymal stem cells, which may provide immunocompatible and noncarcinogenic autologous or allogeneic cell sources;(3) The lifespan of the designer cells inside the alginate microcapsules is an imperative issue. To realize long-term cell therapy, we will further improve the encapsulation technology."Haifeng Ye, Professor at East China Normal University, was speaking with Molly Campbell, Science Writer, Technology Networks.References:1. A green teatriggered genetic control system for treating diabetes in mice and monkeys," by J. Yin; L. Yang; K. Dong; J. Jiang; S. Xue; Y. Xu; X. Wang; H. Ye at East China Normal University in Shanghai, China; L. Mou; Y. Lu at First Affiliated Hospital of Shenzhen University in Shenzhen, China.2. Reygaert. 2018. Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases. Biomed Research International. doi: 10.1155/2018/9105261.

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Green Tea Acts as a "Remote Control" To Switch on Cell Therapy - Technology Networks

An unexpected early morning phone call from the hospital is never good news. When Joy Johnson answered, her first thought was that Sharon Birzer, her partner of 15 years, was dead. Her fears were amplified by the voice on the other end refusing to confirm or deny it. Just come in and talk to one of the doctors, she remembers the voice saying.

Johnson knew this was a real possibility. A few weeks earlier, she and Birzer sat in the exam room of a lymphoma specialist at Stanford University. Birzers cancer had grown, and fast first during one type of chemotherapy, then through a second. Out of standard options, Birzers local oncologist had referred her for a novel treatment called chimeric antigen receptor T-cell therapy or CAR-T. Birzer and Johnson knew the treatment was risky. They were warned there was a chance of death. There was also a chance of serious complications such as multi-organ failure and neurological impairment. But it was like warning a drowning person that her lifeboat could have problems. Without treatment, the chance of Birzers death was all but certain. She signed the consent form.

Johnson hung up the phone that early morning and sped to the hospital. She met with a doctor and two chaplains in a windowless room in the cancer ward, where happy photos of cancer alumni smiled down from the walls. This is getting worse and worse, Johnson thought. As she remembers it, the doctor went through the timeline of what happened for 10 minutes, explaining how Birzer became sicker and sicker, before Johnson interrupted with the thought splitting her world in two: I need you to tell me whether shes alive or dead.

Birzer wasnt dead. But she was far from okay. The ordeal began with Birzer speaking gibberish. Then came seizures so severe there was concern she wouldnt be able to breathe on her own. When it took a few different medications to stop Birzer from seizing, her doctors sedated her, put a breathing tube down her throat, and connected her to a ventilator. Now, she was unconscious and in the intensive care unit (ICU).

Birzer was one of the early patients to receive CAR-T, a radical new therapy to treat cancer. It involved removing Birzers own blood, filtering for immune cells called T-cells, and genetically engineering those cells to recognize and attack her lymphoma. CAR-T made history in 2017 as the first FDA-approved gene therapy to treat any disease. After three to six months of follow-up, the trials that led to approval showed response rates of 80 percent and above in aggressive leukemias and lymphomas that had resisted chemotherapy. Patients on the brink of death were coming back to life.

This is something I often dream of seeing but rarely do. As a doctor who treats cancer, I think a lot about how to frame new treatments to my patients. I never want to give false hope. But the uncertainty inherent to my field also cautions me against closing the door on optimism prematurely. We take it as a point of pride that no field of medicine evolves as rapidly as cancer the FDA approves dozens of new treatments a year. One of my biggest challenges is staying up to date on every development and teasing apart what should and shouldnt change my practice. I am often a mediator for my patients, tempering theoretical promises with everyday realism. To accept a research finding into medical practice, I prefer slow steps showing me proof of concept, safety, and efficacy.

CAR-T, nearly three decades in the making, systemically cleared these hurdles. Not only did the product work, its approach was also unique among cancer treatments. Unlike our usual advances, this wasnt a matter of prescribing an old drug for a new disease or remixing known medications. CAR-T isnt even a drug. This is a one-time infusion giving a person a better version of her own immune system. When the FDA approved its use, it wasnt a question of whether my hospital would be involved, but how we could stay ahead. We werent alone.

Today, two FDA-approved CAR-T products called Kymriah and Yescarta are available in more than 100 hospitals collectively across the U.S. Hundreds of clinical trials are tinkering with dosages, patient populations, and types of cancer. Some medical centers are manufacturing the cells on-site.

The FDA approved CAR-T with a drug safety program called a Risk Evaluation and Mitigation Strategy (REMS). As I cared for these patients, I quickly realized the FDAs concerns. Of the 10 or so patients Ive treated, more than half developed strange neurologic side effects ranging from headaches to difficulty speaking to seizures to falling unconscious. We scrambled to learn how to manage the side effects in real time.

Johnson and Birzer, who I didnt treat personally but spoke to at length for this essay, understood this better than most. Both had worked in quality control for a blood bank and were medically savvier than the average patient. They accepted a medical system with a learning curve. They were fine with hearing I dont know. Signing up for a trailblazing treatment meant going along for the ride. Twists and bumps were par for the course.

* * *

Cancer, by definition, means something has gone very wrong within a cell has malfunctioned and multiplied. The philosophy for fighting cancer has been, for the most part, creating and bringing in treatments from outside the body. Thats how we got to the most common modern approaches: Chemotherapy (administering drugs to kill cancer), radiation (using high energy beams to kill cancer), and surgery (cutting cancer out with a scalpel and other tools). Next came the genetics revolution, with a focus on creating drugs that target a precise genetic mutation separating a cancer cell from a normal one. But cancers are genetically complex, with legions of mutations and the talent to develop new ones. Its rare to have that one magic bullet.

Over the last decade or so, our approach shifted. Instead of fighting cancer from the outside, we are increasingly turning in. The human body is already marvelously equipped to recognize and attack invaders, from the common cold to food poisoning, even if the invaders are ones the body has never seen before. Cancer doesnt belong either. But since cancer cells come from normal ones, theyve developed clever camouflages to trick and evade the immune system. The 2018 Nobel Prize in Physiology or Medicine was jointly awarded to two researchers for their work in immunotherapy, a class of medications devoted to wiping out the camouflages and restoring the immune systems upper hand. As I once watched a fellow oncologist describe it to a patient: Im not treating you. You are treating you.

What if we could go one step further? What if we could genetically engineer a patients own immune cells to spot and fight cancer, as a sort of best hits of genetic therapy and immunotherapy?

Enter CAR-T. The technology uses T-cells, which are like the bouncers of the immune system. T-cells survey the body and make sure everything belongs. CAR-T involves removing a persons T-cells from her blood and using a disarmed virus to deliver new genetic material to the cells. The new genes given to the T-cells help them make two types of proteins. The first giving the technology its name is a CAR, which sits on the T-cells surface and binds to a protein on the tumor cells surface, like a lock and key. The second serves as the T-cells caffeine jolt, rousing it to activate. Once the genetic engineering part is done, the T-cells are prodded to multiply by being placed on a rocking device that feeds them nutrients while filtering their wastes. When the cells reach a high enough number a typical dose ranges from hundreds of thousands to hundreds of millions they are formidable enough to go back into the patient. Once inside, the cancer provokes the new cells to replicate even more. After one week, a typical expansion means multiplying by about another 1,000-fold.

Practically, it looks like this: A person comes in for an appointment. She has a catheter placed in a vein, perhaps in her arm or her chest, that connects to a large, whirring machine which pulls in her blood and separates it into its components. The medical team set the T-cells aside to freeze while the rest of the blood circulates back into the patient in a closed loop. Then, the hospital ships the cells frozen to the relevant pharmaceutical companys headquarters or transports them to a lab on-site, where thawing and manufacturing takes from a few days to a few weeks. When the cells are ready, the patient undergoes about three days of chemotherapy to kill both cancer and normal cells, making room for the millions of new cells and eradicating normal immune players that could jeopardize their existence. She then gets a day or two to rest. When the new cells are infused back into her blood, we call that Day 0.

* * *

I remember the first time I watched a patient get his Day 0 infusion. It felt anti-climactic. The entire process took about 15 minutes. The CAR-T cells are invisible to the naked eye, housed in a small plastic bag containing clear liquid.

Thats it? my patient asked when the nurse said it was over. The infusion part is easy. The hard part is everything that comes next.

Once the cells are in, they cant turn off. That this may cause collateral damage was evident from the start. In 2009 working in parallel with other researchers at Memorial Sloan Kettering Cancer Center in New York and the National Cancer Institute in Maryland oncologists at the University of Pennsylvania opened a clinical trial for CAR-T in human leukemia patients. (Carl June, who led the CAR-T development, did not respond to Undarks interview request.) Of the first three patients who got CAR-T infusions, two achieved complete remission but nearly died in the process. The first was a retired corrections officer named Bill Ludwig, who developed extremely high fevers and went into multi-organ failure requiring time in the ICU. At the time, the medical teams had no idea why it was happening or how to stop it. But time passed. Ludwig got better. Then came the truly incredible part: His cancer was gone.

With only philanthropic support, the trial ran out of funding. Of the eligible patients they intended to treat, the Penn doctors only treated three. So they published the results of one patient in the New England Journal of Medicine and presented the outcomes of all three patients, including Ludwig, at a cancer conference anyway. From there, the money poured in. Based on the results, the Swiss pharmaceutical company Novartis licensed the rights of the therapy.

The next year, six-year-old Emily Whitehead was on the brink of death when she became the first child to receive CAR-T. She also became extremely ill in the ICU, and her cancer was also eventually cured. Her media savvy parents helped bring her story public, making her the poster child for CAR-T. In 2014, the FDA granted CAR-T a breakthrough therapy designation to expedite the development of extremely promising therapies. By 2017, a larger trial gave the treatment to 75 children and young adults with a type of leukemia B-cell acute lymphoblastic leukemia that failed to respond to chemotherapy. Eighty-one percent had no sign of cancer after three months.

In August 2017, the FDA approved a CAR-T treatment as the first gene therapy in the U.S. The decision was unanimous. The Oncologic Drugs Advisory Committee, a branch of the FDA that reviews new cancer products, voted 10 to zero in favor of Kymriah. Committee members called the responses remarkable and potentially paradigm changing. When the announcement broke, a crowd formed in the medical education center of Penn Medicine, made up of ecstatic faculty and staff. There were banners and T-shirts. A remarkable thing happened was the tagline, above a cartoon image of a heroic T-cell. Two months later, in October 2017, the FDA approved a second CAR-T formulation called Yescarta from Kite Pharma, a subsidiary of Gilead Sciences, to treat an aggressive blood cancer in adults called diffuse large B-cell lymphoma, the trial of which had shown a 54 percent complete response rate, meaning all signs of cancer had disappeared. In May 2018, Kymriah was approved to treat adults with non-Hodgkin lymphoma.

That year, the American Society of Clinical Oncology named CAR-T the Advance of the Year, beating out immunotherapy, which had won two years in a row. When I attended the last American Society of Hematology meeting in December 2018, CAR-T stole the show. Trying to get into CAR-T talks felt like trying to get a photo with a celebrity. Running five minutes late to one session meant facing closed doors. Others were standing room only. With every slide, it became difficult to see over a sea of smartphones snapping photos. At one session I found a seat next to the oncologist from my hospital who treated Birzer. Look, she nudged me. Do you see all these non-member badges? I turned. Members were doctors like us who treated blood cancers. I couldnt imagine who else would want to be here. Who are they? I asked. Investors, she said. It felt obvious the moment she said it.

For patients, the dreaded c word is cancer. For oncologists, its cure. When patients ask, Ive noticed how we gently steer the conversation toward safer lingo. We talk about keeping the cancer in check. Cure is a dangerous word, used only when so much time has passed from her cancer diagnosis we can be reasonably certain its gone. But that line is arbitrary. We celebrate therapies that add weeks or months because the diseases are pugnacious, the biology diverse, and the threat of relapse looming. Oncologists are a tempered group, or so Ive learned, finding inspiration in slow, incremental change.

This was completely different. These were patients who would have otherwise died, and the trials were boasting that 54 to 81 percent were cancer-free upon initial follow-up. PET scans showed tumors that had speckled an entire body melt away. Bone marrow biopsies were clear, with even the most sensitive testing unable to detect disease.

The dreaded word was being tossed around could this be the cure weve always wanted?

* * *

When a new drug gets FDA approval, it makes its way into clinical practice, swiftly and often with little fanfare. Under the drug safety program REMS, hospitals offering CAR-T were obligated to undergo special training to monitor and manage side effects. As hospitals worked to create CAR-T programs, oncologists like me made the all too familiar transition from first-time user to expert.

It was May 2018 when I rotated through my hospitals unit and cared for my first patients on CAR-T. As I covered 24-hour shifts, I quickly learned that whether I would sleep that night depended on how many CAR-T patients I was covering. With each treatment, it felt like we were pouring gasoline on the fire of patients immune systems. Some developed high fevers and their blood pressures plummeted, mimicking a serious infection. But there was no infection to be found. When resuscitating with fluids couldnt maintain my patients blood pressures, I sent them to the ICU where they required intensive support to supply blood to their critical organs.

We now have a name for this effect cytokine release syndrome that occurs in more than half of patients who receive CAR-T, starting with Ludwig and Whitehead. The syndrome is the collateral damage of an immune system on the highest possible alert. This was first seen with other types of immunotherapy, but CAR-T took its severity to a new level. Usually starting the week after CAR-T, cytokine release syndrome can range from simple fevers to multi-organ failure affecting the liver, kidneys, heart, and more. The activated T-cells make and recruit other immune players called cytokines to join in the fight. Cytokines then recruit more immune cells. Unlike in the early trials at Penn, we now have two medicines to dampen the effect. Steroids calm the immune system in general, while a medication called tocilizumab, used to treat autoimmune disorders such as rheumatoid arthritis, blocks cytokines specifically.

Fortuity was behind the idea of tocilizumab: When Emily Whitehead, the first child to receive CAR-T, developed cytokine release syndrome, her medical team noted that her blood contained high levels of a cytokine called interleukin 6. Carl June thought of his own daughter, who had juvenile rheumatoid arthritis and was on a new FDA-approved medication that suppressed the same cytokine. The team tried the drug, tocilizumab, in Whitehead. It worked.

Still, we were cautious in our early treatments. The symptoms of cytokine release syndrome mimic the symptoms of severe infection. If this were infection, medicines that dampen a patients immune system would be the opposite of what youd want to give. There was another concern: Would these medications dampen the anti-cancer activity too? We didnt know. Whenever a CAR-T patient spiked a fever, I struggled with the question is it cytokine release syndrome, or is it infection? I often played it safe and covered all bases, starting antibiotics and steroids at the same time. It was counterintuitive, like pressing both heat and ice on a strain, or treating a patient simultaneously with fluids and diuretics.

The second side effect was even scarier: Patients stopped talking. Some, like Sharon Birzer, spoke gibberish or had violent seizures. Some couldnt interact at all, unable to follow simple commands like squeeze my fingers. How? Why? At hospitals across the nation, perfectly cognitively intact people who had signed up to treat their cancer were unable to ask what was happening.

Our nurses learned to ask a standardized list of questions to catch the effect, which we called neurotoxicity: Where are we? Who is the president? What is 100 minus 10? When the patients scored too low on these quizzes, they called me to the bedside.

In turn, I relied heavily on a laminated booklet, made by other doctors who were using CAR-T, which we tacked to a bulletin board in our doctors workroom. It contained a short chart noting how to score severity and what to do next. I flipped through the brightly color-coded pages telling me when to order a head CT-scan to look for brain swelling and when to place scalp electrodes looking for seizures. Meanwhile, we formed new channels of communication. As I routinely called a handful of CAR-T specialists at my hospital in the middle of the night, national consortiums formed where specialists around the country shared their experiences. As we tweaked the instructions, we scribbled updates to the booklet in pen.

I wanted to know whether my experience was representative. I came across an abstract and conference talk that explored what happened to 277 patients who received CAR-T in the real world, so I emailed the lead author, Loretta Nastoupil, director of the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center in Houston. Fortuitously, she was planning a trip to my university to give a talk that month. We met at a caf and I asked what her research found. Compared to the earlier trials, the patients were much sicker, she said. Of the 277 patients, more than 40 percent wouldnt have been eligible for the very trials that got CAR-T approved. Was her team calling other centers for advice? They were calling us, she said.

Patients included in clinical trials are carefully selected. They tend not to have other major medical problems, as we want them to survive whatever rigorous new therapy we put them through. Nastoupil admits some of it is arbitrary. Many criteria in the CAR-T trials were based on criteria that had been used in chemotherapy trials. These become standard languages that apply to all studies, she said, listing benchmarks like a patients age, kidney function, and platelet count. But we have no idea whether criteria for chemotherapy would apply to cellular therapy.

Now, with a blanket FDA approval comes clinical judgment. Patients want a chance. Oncologists want to give their patients a chance. Young, old, prior cancer, heart disease, or liver disease without strict trial criteria, anyone is fair game.

When I was making rounds at my hospital, I never wandered too far from these patients rooms, medically prepared for them to crash at any moment. At the same time, early side effects made me optimistic. A bizarre truism in cancer is that side effects may bode well. They could mean the treatment is working. Cancer is usually a waiting game, requiring months to learn an answer. Patients and doctors alike seek clues, but the only real way to know is waiting: Will the next PET scan show anything? What are the biopsy results?

CAR-T was fundamentally different from other cancer treatments in that it worked fast. Birzers first clue came just a few hours after her infusion. She developed pain in her lower back. She described it as feeling like she had menstrual cramps. A heavy burden of lymphoma lay in her uterus. Could the pain mean that the CAR-T cells had migrated to the right spot and started to work? Her medical team didnt know, but the lead doctors instinct was that it was a good sign.

Two days later, her temperature shot up to 102. Her blood pressure dropped. The medical team diagnosed cytokine release syndrome, as though right on schedule, and gave her tocilizumab.

Every day, the nurses would ask her questions and have her write simple sentences on a slip of paper to monitor for neurotoxicity. By the fifth day, her answers changed. She started saying things that were crazy, Johnson explained.

One of Birzer's sentences was guinea pigs eat greens like hay and pizza. Birzer and Johnson owned two guinea pigs, so their diet would be something Birzer normally knew well. So Johnson tried to reason with her: They dont eat pizza. And Birzer replied, They do eat pizza, but only gluten-free.

Johnson remembers being struck by the certainty in her partners delirium. Not only was Birzer confused, she was confident she was not. She was doubling down on everything, Johnson described. She was absolutely sure she was right.

Johnson vividly remembers the evening before the frightening early-morning phone call that brought her rushing back to the hospital. Birzer had said there was no point in Johnson staying overnight; she would only watch her be in pain. So Johnson went home. After she did, the doctor came by multiple times to evaluate Birzer. She was deteriorating and fast. Her speech became more and more garbled. Soon she couldnt name simple objects and didnt know where she was. At 3 a.m., the doctor ordered a head CT to make sure Birzer wasnt bleeding into her brain.

Fortunately, she wasnt. But by 7 a.m. Birzer stopped speaking altogether. Then she seized. Birzers nurse was about to step out of the room when she noticed Birzers arms and legs shaking. Her eyes stared vacantly and she wet the bed. The nurse called a code blue, and a team of more doctors and nurses ran over. Birzer was loaded with high-dose anti-seizure medications through her IV. But she continued to seize. As nurses infused more medications into her IV, a doctor placed a breathing tube down her throat.

Birzers saga poses the big question: Why does CAR-T cause seizures and other neurologic problems? No one seemed to know. My search of the published scientific literature was thin, but one name kept cropping up. So I called her. Juliane Gust, a pediatric neurologist and scientist at Seattle Childrens Hospital, told me her investigations of how CAR-T affects the brain were motivated by her own experiences. When the early CAR-T trials opened at her hospital in 2014, she and her colleagues began getting calls from oncologists about brain toxicities they knew nothing about. Where are the papers? she remembered thinking. There was nothing.

Typically, the brain is protected by a collection of cells aptly named the blood-brain-barrier. But with severe CAR-T neurotoxicity, research suggests, this defense breaks down. Gust explained that spinal taps on these patients show high levels of cytokines floating in the fluid surrounding the spine and brain. Some CAR-T cells circulate in the fluid too, she said, but these numbers do not correlate with sicker patients. CAR-T cells are even seen in the spinal fluid of patients without any symptoms.

What does this mean? Gust interprets it as a patients symptoms having more to do with cytokines than the CAR-T cells. Cytokine release syndrome is the number one risk factor for developing neurotoxicity over the next few days, she said. The mainstay for neurotoxicity is starting steroids as soon as possible. In the beginning we didnt manage as aggressively. We were worried about impairing the function of the CAR-T, she added. Now we give steroids right away.

But the steroids dont always work. Several doses of steroids didnt prevent Birzer from seizing. The morning after Johnsons alarming phone call, after the meeting at the hospital when she learned what had happened, a chaplain walked her from the conference room to the ICU. The first day, Johnson sat by her partners bedside while Birzer remained unconscious. By the next evening, she woke up enough to breathe on her own. The doctors removed her breathing tube, and Birzer looked around. She had no idea who she was or where she was.

Birzer was like a newborn baby, confused and sometimes frightened by her surroundings. She frequently looked like she was about to say something, but she couldnt find the words despite the nurses and Johnsons encouragement. One day she spoke a few words. Eventually she learned her name. A few days later she recognized Johnson. Her life was coming back to her, though she was still suspicious of her reality. She accused the nurses of tricking her, for instance, when they told her Donald Trump was president.

She took cues from the adults around her on whether her actions were appropriate. The best example of this was her I love you phase. One day, she said it to Johnson in the hospital. A few nurses overheard it and commented on how sweet it was. Birzer was pleased with the reaction. So she turned to the nurse: I love you! And the person emptying the trash: I love you! Months later, she was having lunch with a friend who asked, Do you remember when you told me you loved me? Birzer said, Well, I stand by that one.

When she got home, she needed a walker to help with her shakiness on her feet. When recounting her everyday interactions, she would swap in the wrong people, substituting a friend for someone else. She saw bugs that didnt exist. She couldnt hold a spoon or a cup steady. Johnson would try to slow her down, but Birzer was adamant she could eat and drink without help. Then peas would fly in my face, Johnson said.

Patients who experience neurotoxicity fall into one of three categories. The majority are impaired but then return to normal without long-term damage. A devastating handful, less than 1 percent, develop severe brain swelling and die. The rest fall into a minority that have lingering problems even months out. These are usually struggles to think up the right word, trouble concentrating, and weakness, often requiring long courses of rehabilitation and extra help at home.

As Birzer told me about her months of rehab, I thought how she did seem to fall somewhere in the middle among the patients Ive treated. On one end of the spectrum was the rancher who remained profoundly weak a year after his infusion. Before CAR-T, he walked across his ranch without issue; six months later, he needed a walker. Even with it, he fell on a near weekly basis. On the other end was the retired teacher who couldnt speak for a week she would look around her ICU room and move her mouth as though trying her hardest and then woke up as though nothing happened. She left the hospital and instantly resumed her life, which included a recent trip across the country. In hindsight, I remember how we worried more about giving the therapy to the teacher than the rancher, as she seemed frailer. Outcomes like theirs leave me with a familiar humility I keep learning in new ways as a doctor: We often cant predict how a patient will do. Our instincts can be just plain wrong.

I asked Gust if we have data to predict who will land in which group. While we can point to some risk factors higher burdens of cancer, baseline cognitive problems before therapy the individual patient tells you nothing, she confirmed.

So we wait.

* * *

Doctors like me who specialize in cancer regularly field heart-wrenching questions from patients. They have read about CAR-T in the news, and now they want to know: What about me? What about my cancer?

So, who gets CAR-T? That leads to the tougher question who doesnt? That depends on the type of cancer and whether their insurance can pay.

CAR-T is approved to treat certain leukemias and lymphomas that come from the blood and bone marrow. Since the initial approval, researchers have also set up new CAR-T trials for all sorts of solid tumors from lung cancer to kidney cancer to sarcoma. But progress has been slow. While some promising findings are coming from the lab and in small numbers of patients on early phase trials, nothing is yet approved in humans. The remarkable responses occurring in blood cancers just werent happening in solid tumors.

Cancer is one word, but its not one disease. Its easier to prove why something works when it works than show why it doesnt work when it doesnt work, said Saar Gill, a hematologist and scientist at the University of Pennsylvania who co-founded a company called Carisma Therapeutics using CAR-T technology against solid tumors. That was his short answer, at least. The longer answer to why CAR-T hasnt worked in solid cancers involves what Gill believes are two main barriers. First, its a trafficking problem. Leukemia cells tend to be easier targets; they bob through the bloodstream like buoys in an ocean. Solid tumors are more like trash islands. The cancer cells stick together and grow an assortment of supporting structures to hold the mound together. The first problem for CAR-T is that the T-cells may not be able to penetrate the islands. Then, even if the T-cells make it in, theyre faced with a hostile environment and will likely die before they can work.

At Carisma, Gill and his colleagues look to get around these obstacles though a different immune cell called the macrophage. T-cells are not the only players of the immune system, after all. Macrophages are gluttonous cells that recognize invaders and engulf them for destruction. But studies have shown they cluster in solid tumors in a way T-cells dont. Gill hopes genetically engineered macrophages can be the stowaways that sneak into solid tumor and attack from the inside out.

Another big challenge, even for leukemias and lymphomas, is resistance, where the cancers learn to survive the CAR-T infusion. While many patients in the trials achieved remission after a month, we now have two years worth of data and the outlook isnt as rosy. For lymphoma, that number is closer to 40 percent. Patients celebrating cures initially are relapsing later. Why?

The CAR-T cells we use target a specific protein on cancer cells. But if the cancer no longer expresses that protein, that can be a big problem, and were finding thats exactly whats happening. Through blood testing, we see that many patients who relapse lose the target.

Researchers are trying to regain the upper hand by designing CAR-Ts to target more than one receptor. Its an old idea in a new frame: An arms race between our medicines and the illnesses that can evolve to evade them. Too much medical precision in these cases is actually not what we want, as it makes it easier for cancer to pinpoint whats after it and develop an escape route. So, the reasoning goes, target multiple pieces at once. Confuse the cancer.

Then theres the other dreaded c word: Cost. Novartis Kymriah runs up to $475,000 while Kite Pharmas Yescarta is $373,000. That covers manufacturing and infusion. Not included is the minimum one-week hospital stay or any complications.

They are daunting numbers. Some limitations on health care we accept maybe the patients are too sick; maybe they have the wrong disease. The wrong cost is not one we as a society look kindly upon. And drug companies shy away from that kind of attention.

Cost origins in medicine are notoriously murky. Novartis, confident in its technology, made an offer to offset the scrutiny in CAR-T. If the treatment didnt work after one month, the company said it wouldnt send a bill.

Not everyone agrees that cost is an issue. Gill, for example, believes the concern is over-hyped. Its not a major issue, he told me over the phone. Look, of course [with] health care in this country, if you dont have insurance, then youre screwed. That is no different when it comes to CAR-T as it is for anything else, he said. The cost conversation must also put CAR-T in context. Gill went on to list what these patients would be doing otherwise months of chemotherapy, bone marrow transplants, hospital stays for cancer-associated complications and the associated loss of income as patients and caregivers miss work. These could add up to far more than a one-time CAR-T infusion. A bone marrow transplant, for example, can cost from $100,000 to more than $300,000. The cancer-fighting drug blinatumomab, also used to treat relapsed leukemia, costs $178,000 a year. Any discussion of cost is completely irresponsible without weighing the other side of the equation, Gill said.

How the system will get on board is another question. Logistics will be an issue, Gill conceded. The first national Medicare policy for covering CAR-T was announced in August 2019, two years after the first product was approved. The Centers for Medicare and Medicaid Services has offered to reimburse a set rate for CAR T-cell infusion, and while this figure was recently raised, it remains less than the total cost. Despite the expansion of medical uses, at some centers referrals for CAR-T are dropping as hospitals worry its a net loss. And while most commercial insurers are covering CAR-T therapies, companies less accustomed to handling complex therapies can postpone approval. Ironically, the patients considering CAR-T are the ones for whom the window for treatment is narrowest. A delay of even a few weeks can mean the difference between a cure and hospice.

This, of course, poses a big problem. A breakthrough technology is only as good as its access. A major selling point of CAR-T besides the efficacy is its ease. Its a one-and-done treatment. Engineered T-cells are intended to live indefinitely, constantly on the alert if cancer tries to come back. Compare that to chemotherapy or immunotherapy, which is months of infusions or a pill taken indefinitely. CAR-T is more akin to surgery: Cut it out, pay the entire cost upfront, and youre done.

Birzer was lucky in this respect. I asked her and Johnson if cost had factored into their decision to try CAR-T. They looked at each other. It wasnt an issue, said Johnson. They remembered getting a statement in the mail for a large sum when they got home. But Birzer had good insurance. She didnt pay a cent.

* * *

One year after Birzers infusion, I met her and Johnson at a coffee shop near their home in San Francisco. They had saved a table. Johnson had a newspaper open. Birzer already had her coffee, and I noticed her hand trembling as she brought it to her mouth. She described how she still struggles to find exactly the right words. She sometimes flings peas. But shes mostly back to normal, living her everyday life. She has even returned to her passion, performing stand-up comedy, though she admitted that at least for general audiences: My jokes about cancer didnt kill.

People handed a devastating diagnosis dont spend most of their time dying. They are living, but with a heightened awareness for a timeline the rest of us take for granted. They sip coffee, enjoy their hobbies, and read the news while also getting their affairs in order and staying on the lookout, constantly, for the next treatment that could save them.

Hoping for a miracle while preparing to die are mutually compatible ideas. Many of my patients have become accustomed to living somewhere in that limbo. It is humbling to witness. They hold out hope for a plan A, however unlikely it may be, while also adjusting to the reality of a plan B. They live their lives; and they live in uncertainty.

I see patients in various stages of this limbo. In clinic, I met a man with multiple myeloma six months after a CAR-T trial that supposedly cured him. He came in with a big smile but then quietly began praying when it was time to view PET results. He asked how the other patients on the trial were doing, and I shared the stats. While percentages dont say anything about an individual experience, theyre also all patients have to go on. When someone on the same treatment dies, its shattering for everyone. Was one person the exception, or a harbinger of anothers fate? Who is the outlier?

I look at these patients and think a sober truth: Before CAR-T, all would likely die within six months. Now, imagine taking 40 percent and curing them. Sure, a naysayer might point out, its only 40 percent. Whats the hype if most still succumb to their cancer? But there was nothing close to that before CAR-T. I agree with how Gill described it: I think CAR-T cells are like chemotherapy in the 1950s. Theyre not better than chemotherapy theyre just different. For an adversary as tough as cancer, well take any tool we can get.

There remain many questions. Can we use CAR-T earlier in a cancers course? Lessen the side effects? Overcome resistance? Streamline manufacturing and reimbursement? Will it work in other cancers? Patients will sign up to answer.

For now, Birzer seems to be in the lucky 40 percent. Her one-year PET scan showed no cancer. I thought of our last coffee meeting, where I had asked if she ever worried she wouldnt return to normal. She didnt even pause. If youre not dead, she said, youre winning.

* * *

Ilana Yurkiewicz, M.D., is a physician at Stanford University and a medical journalist. She is a former Scientific American Blog Network columnist and AAAS Mass Media Fellow. Her writing has also appeared in Aeon Magazine, Health Affairs, and STAT News, and has been featured in "The Best American Science and Nature Writing."

This article was originally published on Undark. Read the original article.

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The Possibilities and Risks of Genetically Altering Immune Cells to Fight Cancer - Smithsonian.com

MENLO PARK, Calif., Oct. 24, 2019 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc.,(Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced that the first patient was dosed in the third cohort (n=9) of the ongoing OPTIC phase 1 clinical trial for ADVM-022 for the treatment of neovascular or wet age-related macular degeneration (wet AMD). Patients in this cohort are receiving a single intravitreal injection of gene therapy candidate ADVM-022 at a dose of 2 x 10 ^11 vg/eye.

We are excited to report dosing the first patient in the third cohort of OPTIC. This expansion of OPTIC will generate important clinical data to support the further development of ADVM-022, said Aaron Osborne, MBBS, chief medical officer of Adverum. Based on the recently presented data from the first cohort of OPTIC, which demonstrated a sustained response to a single injection of ADVM-022 out to a median of 34 weeks, with no patient in the first cohort requiring anti-VEGF rescue therapy, we believe that ADVM-022 has the potential to be a transformative treatment option for patients with wet AMD.

Dante Pieramici, M.D., co-director of the California Retina Research Foundation, Managing Partner of The California Retina Consultants and investigator in the OPTIC trial, said, An intravitreal gene therapy that can significantly reduce the number of injections required to maintain vision would be welcomed by patients with wet AMD as well as their caregivers and physicians. Im encouraged by the recently presented clinical data from the first cohort of the OPTIC trial showing that the therapy was safe and well tolerated with no rescue injections required in patients who previously required frequent anti-VEGF injections to control their wet AMD.

About the OPTIC Phase 1 Trial of ADVM-022 in Wet AMDThe multi-center, open-label, phase 1 trial is designed to assess the safety and tolerability of a single intravitreal (IVT) administration of ADVM-022 in patients with wet AMD who are responsive to anti-vascular endothelial growth factor (VEGF) treatment. In the first cohort, patients (n=6) received ADVM-022 at a dose of 6 x 10^11 vg/eye and in the second cohort (n=6) patients received ADVM-022 at a dose of 2 x 10^11 vg/eye. In the third cohort (n=9), patients are receiving ADVM-022 at a dose of 2 x 10^11 vg/eye and in the fourth cohort (n=9), patients will receive ADVM-022 at a dose of 6 x 10^11 vg/eye. Patients in the first and second cohorts received prophylactic oral steroids, while patients in the third and fourth cohorts will receive prophylactic steroid eye drops. The primary endpoint of the trial is the safety and tolerability of ADVM-022 after a single IVT administration. Secondary endpoints include change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST) and macular volume, as well as mean number of anti-VEGF rescue injections and percentage of patients needing anti-VEGF rescue injections. Each patient enrolled in the study will be followed for a total of two years.

Eight leading retinal centers acrossthe United Statesare participating in the OPTIC phase 1 trial for ADVM-022. For more information on the OPTIC phase 1 clinical trial of ADVM-022 in wet AMD, please visithttps://clinicaltrials.gov/ct2/show/NCT03748784.

About ADVM-022 Gene TherapyADVM-022 utilizes a propriety vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. ADVM-022 is administered as a one-time intravitreal injection, designed to deliver long-term efficacy, reduce the burden of frequent anti-VEGF injections, optimize patient compliance, and to improve vision outcomes for wet AMD and diabetic retinopathy patients.

In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for ADVM-022 for the treatment of this disease.

Adverum is currently evaluating ADVM-022 in the OPTIC study, a phase 1 clinical trial in patients 50 years and older with wet AMD. Additionally, Adverum plans to submit an Investigational New Drug Application for ADVM-022 for the treatment of diabetic retinopathy to the U.S. Food and Drug Administration in the first half of 2020.

About Adverum Biotechnologies, Inc.Adverum Biotechnologies (Nasdaq: ADVM) is a clinical-stage gene therapy company targeting unmet medical needs for serious ocular and rare diseases. Adverum is evaluating its novel gene therapy candidate, ADVM-022, as a one-time, intravitreal injection for the treatment of its lead indication, wet age-related macular degeneration. For more information, please visit http://www.adverum.com

Forward-looking StatementsStatements contained in this press release regarding events or results that may occur in the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to statements regarding: Adverums plans for advancing ADVM-022; the potential benefits of ADVM-022: the expected timing of submitting an IND for diabetic retinopathy, all of which are based on certain assumptions made by Adverum on current conditions, expected future developments and other factors Adverum believes are appropriate in the circumstances. Adverum may not achieve any of these in a timely manner, or at all, or otherwise carry out the intentions or meet the expectations disclosed in its forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include risks inherent to, without limitation: Adverums novel technology, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; the results of early clinical trials not always being predictive of future results; the potential for future complications or side effects in connection with use of ADVM-022; obtaining regulatory approval for gene therapy product candidates; enrolling patients in clinical trials; reliance on third parties for conducting the OPTIC trial and vector production; and ability to fund operations through completion of the OPTIC trial and thereafter. Risks and uncertainties facing Adverum are described more fully in Adverums Form 10-Q filed with the SEC on August 8, 2019 under the heading Risk Factors. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Investor and Media Inquiries:

Investors:Myesha LacyAdverum BiotechnologiesVice President, Investor Relations and Corporate Communicationsmlacy@adverum.com1-650-304-3892

Media:Cherilyn Cecchini, M.D.Account Supervisorccecchini@lifescipublicrelations.com1-646-876-5196

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Adverum Biotechnologies Doses First Patient in Third Cohort of OPTIC Phase 1 Clinical Trial of ADVM-022 Intravitreal Gene Therapy for Wet AMDPatients...

NIH launches new collaboration to develop gene-based cures for sickle cell disease and HIV on global scale

The National Institutes of Health plans to invest at least $100 million over the next four years toward an audacious goal: develop affordable, gene-based cures for sickle cell disease (SCD) and HIV. The Bill & Melinda Gates Foundation will also invest $100 million toward this goal. The intention is for these cures to be made globally available, including in low-resource settings.

This initiative follows a bold announcement made earlier this year by President Donald J. Trump during the State of the Union Address to end the HIV epidemic in the United States in the next 10 years.Ending the HIV Epidemic: A Plan for Americaaims to leverage the powerful data and tools now available to reduce new HIV diagnoses in the United States by 75% in five years and by 90% by 2030.The Trump Administration has also elevated the attention paid to sickle cell disease, identifying it as an intractable health challenge with the potential for dramatic advances in the coming years.

Dramatic advances in genetics over the last decade have made effective gene-based treatments a reality, including new treatments for blindness and certain types of leukemia. Yet these breakthroughs are largely inaccessible to most of the world by virtue of the complexity and cost of treatment requirements, which currently limit their administration to hospitals in wealthy countries. To make these treatments effective and available for SCD and HIV, which disproportionately affect populations living in Africa or of African descent, new investment is needed to focus research on the development of curative therapies that can be delivered safely, effectively and affordably in low-resource settings.

The collaboration between the NIH and the Gates Foundation sets out a bold goal of advancing safe, effective and durable gene-based cures to clinical trials in the United States and relevant countries in sub-Saharan Africa within the next seven to 10 years. The ultimate goal is to scale and implement these treatments globally in areas hardest hit by these diseases.

This unprecedented collaboration focuses from the get-go on access, scalability and affordability of advanced gene-based strategies for sickle cell disease and HIV to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries, said NIH Director Francis S. Collins, M.D., Ph.D.We aim to go big or go home.

The collaboration will align aggressive, high-reward research efforts to accelerate progress on shared gene-based strategies to cure SCD and HIV. Both organizations also will continue to invest in other parallel research efforts on cures for SCD and HIV outside of this collaboration.

In recent years, gene-based treatments have been groundbreaking for rare genetic disorders and infectious diseases, said Trevor Mundel, M.D., Ph.D., President, Global Health Program, Bill & Melinda Gates Foundation. While these treatments are exciting, people in low- and middle-income countries do not have access to these breakthroughs. By working with the NIH and scientists across Africa, we aim to ensure these approaches will improve the lives of those most in need and bring the incredible promise of gene-based treatments to the world of public health.

SCD and HIV are major burdens on health in low-resource communities around the world. Approximately 95% of the 38 million people living with HIV globally are in the developing world, with 67% in sub-Saharan Africa, half of whom are living untreated. Fifteen million babies will be born with SCD globally over the next 30 years, with about 75% of those births occurring in sub-Saharan Africa. An estimated 50-90% of infants born with SCD in low-income countries will die before their 5th birthday and SCD is identified as the underlying cause of about 1 in 12 newborn deaths in sub-Saharan Africa.

Collaboration Details

The collaboration will focus on two areas of coordination:

Though SCD, a genetically inherited disease, and HIV, an acquired infectious disease, present significantly different scientific challenges, gene-based treatments hold promise for both, and many of the technical challenges for gene-based cures are expected to be common to both diseases.

To achieve the goals of the collaboration, both projects will require new delivery systems that can get prospective therapies to the right places in the body and optimize treatments to target the cells involved in the respective diseases efficiently and specifically. For SCD, that would mean repairing or compensating for the mutations in hemoglobin that cause SCD in hematopoietic stem cells. For HIV, that would mean targeting the reservoir of proviral DNA that continues to lurk inside a small number of cells, even after many years of effective antiviral treatment.

Such treatments that happen entirely within the body, known asin vivotreatments, would be a major step forward from current treatments, which apply genetic therapies to cells taken outside the body (ex vivo) and then reinfused.

We are losing too much of Africas future to sickle cell disease and HIV, said Matshidiso Rebecca Moeti, M.B.B.S., Regional Director for Africa, World Health Organization. Beating these diseases will take new thinking and long-term commitment. Im very pleased to see the innovative collaboration announced today, which has a chance to help tackle two of Africas greatest public health challenges.

The collaborations goal for SCD is to develop an easy-to-administer, gene-based intervention to either correct the SCD gene mutations or promote fetal hemoglobin gene expression to achieve normal hemoglobin function. The path to a cure will rely in part on the development of gene-based delivery systems capable of selectively targetinghematopoietic stem cells. This will result in the precise correction of gene mutations or addition of a gene to promote sufficient levels of normal hemoglobin expression and function.

Our excitement around this partnership rests not only in its ability to leverage the expertise in two organizations to reduce childhood mortality rates in low-resource countries, but to bring curative therapies for sickle cell disease and HIV to communities that have been severely burdened by these diseases for generations, said Gary H. Gibbons, M.D., Director, National Heart, Lung, and Blood Institute (NHLBI), part of the NIH.A persons health should not be limited by their geographic location, whether rural America or sub-Saharan Africa; harnessing the power of science is needed to transcend borders to improve health for all.

In addition, more needs to be done to understand the burden of SCD in sub-Saharan Africa and to screen newborns for SCD in high-risk geographic areas. NHLBI has already begun to establish a clinical research infrastructure in sub-Saharan Africa. However, additional clinical research and capacity-building efforts are needed to deliver point-of-care screening, such as at the time of infant vaccinations, and to initiate a standard of care. These activities will be undertaken by NIH and Gates Foundation outside of the collaboration, but will support collaboration efforts.

Nearly 38 million people worldwide are living with HIV, with 770,000 deaths due to AIDS in 2018 alone. Like SCD, people in sub-Saharan Africa face a disproportionate risk of HIV. Antiretroviral therapy is highly effective and has made it possible for people with HIV to live long, healthy lives without transmitting the disease to sexual partners. However, treatment must be maintained for a lifetime. A low-cost, safe, effective and durable cure that also prevents reinfection upon sexual exposure has long been a goal to curb the HIV global pandemic.

A number of approaches will be considered to meet the goal of a scalable HIV cure. Both the Gates Foundation and National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, are already funding cure research, exploring gene-based treatments in concert with long-acting therapeutics, monoclonal antibodies and other immune-based targets. This collaboration will allow the partners to intensify and better coordinate ongoing research efforts on these strategies, accelerating studies into early phase clinical trials to safely test promising tools and interventions.A particularly appealing approach is to identify the location of the reservoir of infected cells that still harbor integrated HIV genomes after treatment and target those DNA sequences with gene editing technology.

This collaboration is an ambitious step forward, harnessing the most cutting-edge scientific tools and NIHs sizable global HIV research infrastructure to one day deliver a cure and end the global HIV pandemic, said NIAID Director Anthony S. Fauci, M.D. We are taking into account those with the greatest need at the foundation of this effort, to ensure that, if realized, this exceptional public health achievement will be made accessible to all.

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NIH, Gates Foundation partner for gene-based cures - BSA bureau

LONDON--(BUSINESS WIRE)--The report, global age-related macular degeneration (AMD) therapeutics market has been added to Technavios catalog. It provides a comprehensive analysis of the market, including its global and regional market share as well as market segmentation based on type and geography for the forecast period 2019-2023.

To learn more about the global trends impacting the future of market research: Download Free Sample Report

This report on the age-related macular degeneration (AMD) therapeutics market includes:

Age-related macular degeneration (AMD) therapeutics market analysis and forecast 2019-2023: Features

Age-Related Macular Degeneration (AMD) Therapeutics Market 2019-2023: Competitive Landscape

Age-Related Macular Degeneration (AMD) Therapeutics Market 2019-2023: Geographic Landscape

Age-Related Macular Degeneration (AMD) Therapeutics Market 2019-2023: Type Landscape

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High prevalence of AMD will drive the age-related macular degeneration (AMD) therapeutics market

The prevalence of AMD is increasing significantly, owing to the presence of high-risk factors such as aging, smoking, high cholesterol, and high blood pressure. Moreover, despite the high prevalence of AMD, no approved therapies are available in the market for the treatment of the condition. Thus, the high prevalence coupled with the huge unmet medical need of dry AMD are expected to drive market growth during the forecast period.

Development of gene therapy for AMD An emerging trend in the osteoporosis market

At present, only a few drugs are approved for the treatment of AMD. However, the side effects associated with them are very severe, and the majority of them act against VEGF only. Hence, there is a huge unmet need for safe and novel drugs to treat AMD. The currently available anti-VEGF therapies require repetitive and inconvenient intraocular injections. Hence, several companies are working on novel drugs to combat AMD, among which gene therapy is expected to cure the disease effectively. Hence, the development of gene therapy is expected to be a positive trend for the global AMD therapeutics market.

Other Key Topics Covered in the Report are:

MARKET LANDSCAPE

MARKET SIZING

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Growth of Age-Related Macular Degeneration (AMD) Therapeutics Market to be Impacted by the Development of Gene Therapy for AMD | Technavio - Business...

NOVATO Oct 24, 2019 (Thomson StreetEvents) -- Edited Transcript of Biomarin Pharmaceutical Inc earnings conference call or presentation Wednesday, October 23, 2019 at 8:30:00pm GMT

* Daniel K. Spiegelman

BioMarin Pharmaceutical Inc. - Executive VP & CFO

* Henry J. Fuchs

BioMarin Pharmaceutical Inc. - President of Worldwide Research & Development

BioMarin Pharmaceutical Inc. - Chairman & CEO

BioMarin Pharmaceutical Inc. - Executive VP & Chief Commercial Officer

BioMarin Pharmaceutical Inc. - VP of IR

SVB Leerink LLC, Research Division - MD of Rare Diseases & Senior Research Analyst

* Philip M. Nadeau

William Blair & Company L.L.C., Research Division - Co-Group Head of Biopharma Equity Research

Welcome to the BioMarin's Third Quarter 2019 Financial Results Conference Call. Hosting the conference call today from BioMarin is Traci McCarty, Vice President, Investor relations. Please go ahead, Traci.

Traci McCarty, BioMarin Pharmaceutical Inc. - VP of IR [2]

Thank you, Grace. Thank you, everyone, for joining us today. To remind you, this nonconfidential presentation contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including expectations regarding BioMarin's financial performance, commercial products and potential future products in different areas of therapeutic research and development. Results may differ materially depending on the progress of BioMarin's product programs, actions of regulatory authorities, availability of capital, future actions in the pharmaceutical market and developments by competitors, and those factors are detailed in BioMarin's filings with the Securities and Exchange Commission such as 10-Q, 10-K and 8-K reports.

On the call today from BioMarin's management team are J.J. Bienaim, Chairman and Chief Executive Officer; Henry Fuchs, President of Worldwide Research and Development; Dan Spiegelman, Executive Vice President and Chief Financial Officer; Robert Baffi, President of Global Manufacturing and Technical Operations; and Jeff Ajer, Executive Vice President and Chief Commercial Officer. Consistent with the last 2 quarterly calls, we intend to keep this call to 1 hour in length. If we do not get to your question, please send me an e-mail or give me a call and we'll get right back to. Thank you for your understanding. Now I'd like to turn the call over to our Chairman and CEO, J.J. Bienaim.

Jean-Jacques Bienaim, BioMarin Pharmaceutical Inc. - Chairman & CEO [3]

--------------------------------------------------------------------------------

Thank you, Traci. Good afternoon, and thank you for joining us on today's call. We are proud to share our highest quarterly revenue results to date at BioMarin, a record $461 million in revenues in the third quarter, which represents an 18% growth over the third quarter of last year and demonstrates the increasing strength of our base business. And while we are excited about our next-generation products valrox and vosoritide, we never lose sight of the importance of our existing products to both the people who rely on them to improve their health and to the financial health of our business. In these unpredictable times, this is reassuring that between our strong balance sheet and excellent commercial business, we are not reliant on the financial markets.

As we round out 2019, confidence in our base business combined with R&D expense management, we've also been tightening our both GAAP and non-GAAP guidance to the top of the range for the full year. Our continued commitment to grow our profitability was demonstrated by cash generated in the third quarter, which was just over [$30] million. In addition to our strong base business, the potential returns from our investments in valrox and vosoritide are on the horizon. Approximately 3 years ago, we laid out a 5-year plan for financial success of the business, and we remain on track. We said that R&D expenses as a percentage of revenues would peak and then come down. Over the last 3 years, it has come down from 60% to 43% of revenues and on its way to our long-term goal of 25%, all while preserving a high level of productivity from our R&D engine. Our top line has grown 15% or more year-over-year with a $2 billion revenue target for 2020. And valrox and vosoritide should see growth well beyond that after 2020.

And of course, we have been focusing on the bottom line as well. In 2016, we said that we would be non-GAAP positive starting in 2017. We were non-GAAP positive in 2017, and we have continued to grow each year. Our next target is GAAP profitability, and from here, with the success we anticipate from valrox and vosoritide profit and significantly profitable growth is on the horizon. We are all aware of recent market volatility and the negative impacts it has had on our shareholders in the short term.

However, with a potential business payoff of our strategies in full view, we remain steadfast in our focus to get valrox and vosoritide approved and launched. And with over $1 billion in cash and investments, our 2 potential blockbusters on the horizon and a third already on the market which is Palynziq, we are poised to leverage the R&D, commercial and manufacturing expertise and capabilities established over the last several years.

At the heart of our business and what creates our growth opportunities is our R&D engine. And with that in mind, we look forward to hosting you at our Annual R&D day in New York on November 14, where we will provide updates on our late-stage programs as well as shine a light on the next potential growth drivers beyond valrox and vosoritide. We will also have an interesting lineup of preclinical candidates to share with you. As we can see, the lease programs will be added next to our development pipeline. Please email the IR team for further details, and we hope you will be able to join us. Now I would like to turn the call over to Jeff who will provide more details on the commercial business in the quarter and our expectations for the remainder of the year. Jeff?

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Jeffrey Robert Ajer, BioMarin Pharmaceutical Inc. - Executive VP & Chief Commercial Officer [4]

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Thank you, J.J. As J.J. mentioned, the third quarter was record-breaking in terms of revenue for BioMarin driven by a strong revenue quarter for Vimizim and $30 million in revenue growth from our newest brands, Palynziq and Brineura. Globally, BioMarin's commercial brands contributed $428 million, a 19% increase quarter-over-quarter and $1.2 billion year-to-date or 14% year-over-year growth. I will detail the breakdown of individual product contributions, but we'll start with a positive development in Brazil, a major market for our MPS brands. In the third quarter, we recognized the first installment of a 12-month supply agreement with the Brazilian Ministry of Health for both Vimizim and Naglazyme, which combined for a total contribution of $45 million. This new 1-year supply agreement should result in more revenue predictability through Q2 of 2020, although there will still be uneven order patterns quarter-to-quarter. Importantly, under this new arrangement with the Brazilian Ministry of Health, we would expect the majority of the roughly $90 million contract to be applied in 2019.

And now a little more detail on Vimizim globally. Quarterly revenue of $164 million represented the year-over-year increase of 33%. While a large Brazil order was a major factor in the quarter, patient growth of 11% globally also contributed to the increased and will support long-term additional revenue growth. For the full year, we are tightening our guidance to between $540 million and $570 million. For Naglazyme, the revenues driven from Brazil were offset by decreases due to ordering patterns in the EUMEA region, and thus, Q3 revenue totaling $94 million was down 4% versus Q2. Despite the neutralizing effect of both the favorable and unfavorable ordering in this quarter, overall patient growth remained steady, and we expect consistent annual revenue growth will continue. For the full year, we see revenues tightening to between $360 million and $380 million tightening the range.

Turning now to the PKU brands and starting with Palynziq. In the U.S., July marked the 1-year milestone of drug availability post FDA approval and the trajectory of patient referrals and correlating revenues are meeting expectations across all metrics. Q3 revenues of $24 million, essentially all of which came from U.S. sales, were driven by a combination of the growing number of patients, who have now achieved once-daily dosing and new patients initiating therapy. A reminder that it takes, on average, 5 months for a patient referral to get to commercial therapy and then to daily dosing, at which point, that patient is a material revenue driver.

At the end of Q3 in the United States, there were 670 patients on Palynziq commercial therapy, 142 of those patients from clinical studies and 528 patients formally naive to Palynziq. There were an additional 153 enrolled naive patients who have not yet received their first commercial dispense. A total of 823 adult PKU patients therefore either already being treated with commercial Palynziq or well on their way to their first shipment.

Turning our attention now to the EU launch. In May 2019, we announced approval for Palynziq by the EMA, and since that time, have engaged in very active education efforts, preparation of reimbursement dossiers and promotional activities in first-priority markets. I'm happy to share that physicians are treating patients now in Germany, the first EU country to market. Without the benefit of patients transitioning from clinical trial, in combination with the timing required to achieve reimbursement approvals, we expect that it will take time to realize material revenue contributions from Europe. We're very happy with the progress that we've made to date, and we've reaffirmed revenue guidance for Palynziq tightening range.

Shifting now to Kuvan. Global revenues in the third quarter totaled $121 million, representing a 6% increase year-over-year. The majority of this was due to patient growth in the United States and achieved in parallel through changing patient demographics as more adult PKU patients now have the option to treat with Palynziq. We are adjusting up our full year guidance for Kuvan.

Finally, an update on Brineura. Net product revenues were $20 million in Q3 driven by patient uptake in diverse global market across all 4 regions. Our teams continue to focus their efforts on driving early diagnosis and identifying new patients who will benefit from therapy, coupled with unlocking reimbursement in countries around the world. As a result of these efforts, Brineura has exhibited steady growth over time and now is reaching the level of material revenue contributions on a quarterly basis. We expect continued growth going forward and reaffirm our guidance for Brineura.

In conclusion, I'm very pleased with the commercial team's execution and performance in the third quarter of 2019 in all 4 regions and excited to track and report the progress of the launch of Palynziq in EU. For the remainder of the year, with our established commercial base business, we are confident in our ability to achieve full year revenue guidance of approximately $1.7 billion. So thank you. And now I'd like to turn the call over to Hank.

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Henry J. Fuchs, BioMarin Pharmaceutical Inc. - President of Worldwide Research & Development [5]

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Thanks, Jeff, and congratulations to you and your team. Starting with valrox for adults with severe hemophilia A, an exciting new regulatory development has been announced today. We are pleased to share that the European Medicines Agency has recently granted our request for accelerated assessment of valrox. In their assessment report, the European Medicines Agency acknowledged valrox's potential to address the existing unmet need by providing patients with a treatment option that only requires a single intravenous administration and then subsequently is expected to provide steady levels of endogenously produced coagulation factor VIII for a substantial amount of time. This decision is particularly important because it shows that based on the data the EMA has already received, EMA recognizes valrox's potential as a product of major interest for public health and therapeutic innovation. This decision is also important as the accelerated assessment procedure reduces the timeframe for the European Medicine Agency commitment -- Committee for Medicinal Products for Human Use (CHMP) to review our planned marketing authorization application for valrox on track for later this year. Needless to say, we are gratified to accept this recognition of valrox given the impact it could have for patients with severe hemophilia A.

Another positive development we want to share is the news that our Shanbally facility has been successfully inspected by the Irish HPRA for testing and release of gene therapy products. These newly constructed laboratories are part of our overall strategy for meeting worldwide regulatory requirements for product distribution. This added capability prepares us to meet in-country testing requirements for the release of commercial product in the EU region.

We continue to expect to submit marketing applications in both the United States and Europe in this quarter based on recent meetings with the FDA and EMA as we announced earlier in this quarter. These submissions were based on the recently completed Phase III interim analysis and the updated 3-year Phase I/II data of patients treated with valoctocogene roxaparvovec. Enrollment in the generate I Phase III open-label study is expected to complete mid-November, with the 52-week results anticipated in that study at the end of 2020. As we have said previously, although the trial is open-label, we have a data access plan in place, which is designed to significantly mirror a blinded trial. This precludes anyone not directly monitoring the trial to access any emerging data from this study, and we are not updating any of our prior analyses. As for the ongoing Phase II study, we intend to share a 4-year update with a 6e13 dose as well as a 3-year update on a 4e13 dose at the middle of next year at an appropriate medical conference.

Turning to our next late-stage program, vosoritide for children with achondroplasia is finished -- nearing the finish line. Our global multipronged program has been designed to achieve maximum clinical benefit for infants and children with achondroplasia from newborns through growth plate closure. Beginning with the Phase III program, results from the large global study that includes children from ages 5 to 18 are -- the data are expected by the end of the year. Needless to say, we look forward to sharing all these top line results with you at that time. Another key component of our global program in achondroplasia is the Phase II, 0-5 year old study. Given our conviction and the opinion stated at the achon AdCom meeting that the FDA held earlier in the year and last year, treatment with vosoritide started as early as possible may translate into the best results for children with achondroplasia. We're thrilled with the progress of this ongoing study. We have completed enrollment in the first cohort of the study, which includes children from 2 to 5 years of age. The second cohort, which includes children from 6 months of age through 2 years of age, is expected to complete by the year end and the last cohort of the study, which includes newborns through 6 months of age, began earlier enrolling this month. Needless to say, the level of interest from families seeking treatment for their very young children is very consistent with our belief in starting treatment as early as possible. We hope to provide more insight and detail in this program at R&D day.

Turning to BMN 307, our investigational gene therapy for PKU, we are pleased to have received orphan designation for BMN 307 this past Monday from the FDA. As you likely saw in our recent press release, we submitted a clinical trial application, or CTA, with the Medicines and Healthcare Product Regulatory Agency in the United Kingdom, or the HPRA -- sorry, the MHRA for BMN 307. We expect to start enrolling patients with material manufactured with a commercial-ready process to derisk the program to facilitate rapid clinical development in the Phase I/II trial in early 2020, and we are actively preparing regulatory submissions for other countries. We are excited about the prospect of BMN 307 as it represents a potential third PKU treatment option in our PKU franchise and a second gene-therapy development program, leveraging our learnings and capabilities from valrox.

And finally, on pipeline changes. We announced today that we have entered into a licensing agreement with Allievex for Tralesinidase Alfa, formally BMN 250, an investigational enzyme-replacement therapy for the treatment of Sanfilippo Syndrome Type B. As we've stated previously, our focus is shifting to larger indications where we can have an impact with our highly integrated products so we are thrilled to have Allievex now shepherding the continued development of Tralesinidase Alfa. We couldn't be happier for patients and their families as we expect they will benefit tremendously from Allievex's focus on treatments for rare neurogenerative diseases. We look forward to hosting you at our upcoming R&D day on November 14 in New York, where we will showcase our next potential commercial products, namely valrox and vosoritide including some baseline data never shared before. Another highlight will include an updated look at the natural history information, including trends of vosoritide treatment through 54 months as well as evaluation of untreated patients with achondroplasia. With our earlier-stage pipeline, we look forward to sharing a preview of the next potential INDs we are considering for development. We hope you will attend, so please reach out to our IR department should you need more information. Thank you for continued support, and I'll now call -- turn the call over to Dan to review the financial quarters. Dan?

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Daniel K. Spiegelman, BioMarin Pharmaceutical Inc. - Executive VP & CFO [6]

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Thank you Hank. Please refer to today's press release summarizing our financial results for full details on the third quarter. First, with respect to revenues, we reported total revenues in the quarter of $461 million and are on track for full year 2019 revenues of approximately $1.7 billion, being in the expected range of $1.69 billion to $1.72 billion. In addition to tracking towards the middle of the range for full year total product revenues, as J.J. mentioned, we expect both GAAP and non-GAAP results to be at the top end of the ranges due to continued R&D expense management as we continue to improve overall margins. An important item of note for the quarter is the impact of foreign exchange on our financial results. Over the past year, the dollar has strengthened materially against the Euro and the British pound and even more significantly against several of the Latin American currencies. Overall, net of our hedging, full year revenue is projected to be negatively affected by approximately $20 million to $25 million such that our full year revenue would have been at the high end of our guidance instead of the midrange without these negative FX impacts. Thanks to our hedging contracts, which offset more than half of the potential revenue impact from the strengthening dollar and natural expense hedge offsets, full year bottom line forecasted results are not materially impacted this year by exchange rates.

One specific revenue item that Jeff did not discuss was Aldurazyme revenue in the quarter. It increased by $17 million versus 2Q due to delays in that quarter with Sinofi's QA release that has since been resolved. Year-to-date, Aldurazyme is down $44 million due to a onetime (inaudible) of revenue in Q1 2018 though patients on therapy, as reported by Genzyme, continue to grow in 2019 versus 2018.

Moving to operating expenses. Both R&D and SG&A expenses in the third quarter roughly track to previously provided full year guidance. SG&A is expected to come in at the upper end of the range between $670 million and $690 million. SG&A expenses in the third quarter were impacted by the expansion of sales and marketing capabilities as we launched Palynziq in Europe and continue to prepare for valrox and vosoritide approvals and launch.

In the third quarter, R&D expenses reflect the continued enrollment of additional patients in the global Phase III Generate I study, the manufacturing of BMN 307, our PKU gene therapy product, ahead of clinical trials early next year and the children in the 0 to 5-year-old study with vosoritide.

However, despite the progress of these later-stage development programs, with the decision not to pursue development of both BMN 270 for Frie -- 290, I'm sorry, for Friedreich's ataxia and BMN 250, we now expect R&D expense for the full year to be lower than previously guided. For the full year, we now expect R&D expenses of between $710 million and $740 million.

Turning to BioMarin results. GAAP net income in the third quarter was $55 million as compared to a GAAP net loss of $12.6 million in the third quarter of 2018. GAAP net income in the third quarter increased primarily due to a net profit from operations and a benefit from income taxes of approximately $45 million. For the full year, we expect GAAP loss to come in at the low end of our initial guidance range and now expect the loss of between $65 million and $45 million.

As you know, we also measure our performance on a non-GAAP basis, which is based on EBITDA and also excludes stock compensation, contingent consideration and certain other specified items. Our non-GAAP income in the third quarter was $78 million compared to non-GAAP income of $61 million in the third quarter of 2018. We are now narrowing the range of full year non-GAAP income to be between $150 million and $170 million. The use of cash, cash equivalents and investments as of September 30, 2019, we have $1.15 billion as compared to $1.1 billion on June 30, 2019.

And finally, a note on our cash flows for the third quarter. Year-to-date cash used for operational activities totaled just about $9 million, whereas cash generated by operating activities for the third quarter were just over $70 million. GAAP profitability and continued cash flow growth are expected as our revenues increase. Our P&L structure is expected to be similar to our larger biotech peers we aspire to follow.

In closing, BioMarin's current commercial business remains on track to deliver roughly $1.7 billion in revenues this year and close to $2 billion next year, with increasing GAAP and non-GAAP bottom line profitability. Over the next 18 months, we also expect to accelerate into the next phase of higher revenue and growth through potential approvals of valrox and vosoritide, which could lead to approvals and revenue contributions starting before the end of 2020.

Thanks for your support, and I will now open it to your questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) Your first question comes from the line of Salveen Richter from Goldman Sachs.

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Salveen Jaswal Richter, Goldman Sachs Group Inc., Research Division - VP [2]

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So for vosoritide, how should we think about the clinical meaningfulness of the Phase III data? So while you showed about a 2-centimeter a year benefit at the same dose in the Phase II, clearly, there is a range for various stratification measures that adds up here or gets you on a normal growth curve. So if you can give us any clarity there, and I have a follow-up.

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Henry J. Fuchs, BioMarin Pharmaceutical Inc. - President of Worldwide Research & Development [3]

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Salveen, the clinical meaningfulness of just the Phase III study I don't think can be considered in isolation because the Phase III study is a relatively short duration of 1 year, in that, it's placebo-controlled, and that was what we and our investigators agreed was feasible to study and generate high-quality data. I think the way to think about clinical meaningfulness of vosoritide is in terms of cumulative effect over chronic therapy. And to remind you, we reported last year the accumulated benefit of vosoritide through 42 months of chronic therapy in our Phase I/II cohort of 10 patients. This year, we'll be giving you another update on that, which will now carry patients through 54 months of therapy. And as I mentioned in my talking points, we are now in a position to start addressing what the height gain over untreated patients can be expected to be given that we're now coming online with our own contemporaneous natural history study. So all that taken together says the value of the Phase III trial is to prove that vosoritide is effective compared to placebo. But the magnitude of the benefit should be weighed in the context of longer-term therapy.

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Salveen Jaswal Richter, Goldman Sachs Group Inc., Research Division - VP [4]

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That was helpful. And then can you discuss the forward trajectory and dynamics for Kuvan? Do you expect the majority of patients here to transition over to Palynziq prior to IP expiration?

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Jeffrey Robert Ajer, BioMarin Pharmaceutical Inc. - Executive VP & Chief Commercial Officer [5]

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Salveen, it is certainly our goal to transition as many adult Kuvan patients to Palynziq as possible before loss of exclusivity in a year, and we are making a lot of progress. 38% of our Palynziq referrals, our naive Palynziq patient referrals, are Kuvan transitions, so making a lot of progress there. It is also true that though there remain a smaller now number of new adult patients that are being referred in for Kuvan treatment, and it is also true, particularly in the United States, that our pediatric population is growing on Kuvan. So the trajectory, I would think, would be similar to what we are reporting year-to-date with patient growth of about 6% tied to continued revenue growth. Our focus, both in Europe and the United States, is overwhelmingly now on adult patients gaining access to, and benefiting from, Palynziq therapy.

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Jean-Jacques Bienaim, BioMarin Pharmaceutical Inc. - Chairman & CEO [6]

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Salveen, I'm sorry, just want to remind you on the line that the loss of exclusivity in Q4 of next year is only in the U.S. In Europe, in ex U.S. we have protection until 2024. I'd also give you one point that maybe it's no different from your traditional generic modeling is that when you've a small molecule, you lose protection of market exclusivity. When you lose a patient to a generic they very rarely come back to the brand, if ever. In our case, what in the case we do starting in Q4 2020, October, November 2020. If we do lose a Kuvan patient to a generic, they are not lost forever to our business in the sense that they can always go to Palynziq down the road, so they are not lost forever.

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Operator [7]

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Your next question comes from the line of Phil Nadeau from Cowen and Company.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [8]

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One on vosoritide for me also. In the Phase II data, we saw at month 12, just below a 50% increase in annualized growth velocity. Hank, is there any reason why we shouldn't expect that in the Phase III? Are there any notable differences in the patient populations who are enrolled that could change the expected results?

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Henry J. Fuchs, BioMarin Pharmaceutical Inc. - President of Worldwide Research & Development [9]

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Not really, no. We purposely kept the eligibility criteria fairly consistent and also the outcome measures, between the outcome measure and the dose and regimen are the same so we should expect a fairly similar result. Now the one thing that we've pointed out is that we've been doing those calculations compared to the baseline run in. But as you -- as people have pointed out and as you noticed from (inaudible) achondroplasia growth studies, there is a gentle negative slope so at 1 year, there could be some negative placebo effects, such that we underestimated that 1 year the magnitude in treatment benefit of vosoritide. And I think that's going to get to be more and more important as you go out farther and farther in time because those declines will start to add up. And I was suggesting that at the R&D day, we'll have an opportunity to look at those, both of those phenomena, the chemo derived benefit from product treatment as well as contrast that to similar populations of patients who have not been treated with vosoritide.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [10]

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Got it. Okay. And even though the age 5 to 14 is exactly the same between Phase II and Phase III, do you know whether the people who are actually enrolled have a similar age characteristic? So was the Phase II weighted towards younger patients and Phase III is getting older patients or as far as you know, the ages in the trial are also identical?

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Henry J. Fuchs, BioMarin Pharmaceutical Inc. - President of Worldwide Research & Development [11]

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Read the original:
Edited Transcript of BMRN earnings conference call or presentation 23-Oct-19 8:30pm GMT - Yahoo Finance

Regeneron will lose out on hundreds of millions of dollars if a rival to its top-selling drug performs the way Wall Street expects. Even more would be at risk if recently proposed changes to government insurance become a reality.

In these situations, when a drugmaker's biggest product is under fire, acquisitions can look like an attractive way to put out the flames. AbbVie's $63 billion bid to acquire Allergan stems almost entirely from the buyer trying to find new revenue streams before generics start eating away at its mega-blockbuster drug, Humira.

But Regeneron isn't like other drugmakers. In the 30 years since its founding, it has never acquired another company. Though Regeneron isn't completely shut off to the idea of doing M&A, there's little to indicate the biotech is actively trying to change its deal track record.

Regeneron maintains that it doesn't need to buy drugs because of its R&D skills. Under the direction of CEO Len Schleifer and Chief Scientific Officer George Yancopoulos, the biotech has brought seven new medicines to market, including five from a long-standing partnership with Sanofi.

"When I look at Gilead, for example, or even Biogen [there is] a lot of investor pressure to buy something," Evan Seigerman, a Credit Suisse analyst, told BioPharma Dive. "Regeneron is still good at telling the narrative that 'we can develop our own assets and we have the best capabilities, so we're not going to buy anything.'"

The biggest of those assets is Eylea, a drug for multiple eye diseases that hit $6.75 billion in global sales last year.

For 2019, the average Wall Street estimate has Eylea reaching $7.43 billion in sales. For 2020 and beyond, however, analysts are torn about how it will fare in light of a new competitor.

*Selection of four investment bank forecasts for global Eylea sales

Earlier this month, Novartis began selling in the U.S. a drug for wet AMD, an age-related vision loss disease for which Eylea is also approved. Novartis on its third quarter earnings call touted how the drug, Beovu, is off to a strong launch, though the company didn't provide sales numbers.

While some analysts initially viewed Beovu's label as weaker than expected Christopher Raymond of Piper Jaffray called the drug "little more than an also-ran" it is still poised to steal market share from Eylea. Just how much share is the big question facing Regeneron.

RBC Capital Markets' research team said it recently spoke with an eye specialist who plans on switching one-third of her Eylea-treated wet AMD patients to Beovu. On a broader scale, the American Society of Retina Specialists found in a recent survey of 1,009 people from ophthalmology organizations that 50% plan on prescribing Beovu for wet AMD patients who don't adequately respond to drugs like Eylea or Roche's Lucentis.

Beovu may not be the only challenge to Eylea, either. President Donald Trump and Democrats in the House of Representatives have pitched different plans that would affect how Medicare pays for certain drugs. Medicare Part B spends more on Eylea than any other drug, leaving it particularly exposed if changes to government insurance take shape.

Amid these uncertainties, Regeneron's share price has fallen 16% since the beginning of the year. By contrast, the Nasdaq Biotechnology Index, which includes Regeneron, rose 13% over the period.

"They really do have quite a successful R&D engine," Kennen MacKay of RBC said. "But with the stock trading where it is, maybe there's a feeling that's no longer enough."

Jacob Bell / BioPharma Dive, market data

Regeneron's success is tied to its prowess in developing monoclonal antibodies a type of drug that, while a novelty in the past, is now a mainstay of many drugmakers' pipelines.

Some on Wall Street fret that Regeneron's competitive edge may have weakened as more companies entered this space. Last month, Geoffrey Porges of SVB Leerink went so far as to pose the provocative question: "Is Regeneron becoming the TiVo of biopharma?"

Whether or not those worries are valid, analysts can't envision Regeneron buying anything because that would be so out of character.

"These companies really do have a certain genetic makeup of what they're about, especially Regeneron," Cowen & Co.'s Yaron Werber told BioPharma Dive. "Doing M&A is not something that's in their DNA."

The threats to Eylea are therefore unlikely big enough or realized enough to push Regeneron toward acquisitions. According to consensus figures provided by Credit Suisse, analysts envision sales of the eye drug growing over the next year in spite of Beovu, as it takes greater market share in areas like diabetic macular edema.

Investors also have other bright spots to keep their attention off M&A. Dupixent, a treatment for eczema and asthma, achieved triple-digit growth over the last year and could help offset future hits to Eylea.

Regeneron's pipeline drugs, meanwhile, face significant competition.Roche and Amgen are working on rival cancer agents, while Merck & Co., Bristol-Myers Squibb and Alexion Pharmaceuticals already market blockbuster drugs for diseases that Regeneron is targeting.

"There's a deep pipeline, but it's lacking that one disruptive product that investors always want to see," Werber said. "It's a pipeline that still is getting defined."

Regeneron could find that disruptive product through bets on newer technologies. The company entered a gene editing deal with Intellia Therapeutics in 2016, a cell therapy deal with Bluebird bio in 2018, and an RNA-focused deal with Alnylam Pharmaceuticals this April.

"There's nothing inherently good about doing M&A."

Nouhad Husseini

Head of Business Development, Regeneron

While Regeneron has favored partnerships to acquisitions, it could do the latter if it wanted. By the end of June, the company held just over $1 billion in cash and cash equivalents and another $4.5 billion in marketable securities.

"The deal we did with Alnylam, or Intellia, or any of our partners where we're accessing external innovation, we could have just as easily decided to acquire one of those companies," Nouhad Husseini, Regeneron's head of business development, said in an interview.

Husseini holds reservations about outright acquisitions, though he said he could see Regeneron buying something in the short- or medium-term. Collaborations have worked out well, he notes, because both sides can stay focused on the science without getting distracted by the upheaval that often comes from M&A.

"The way I look at it is: M&A and doing a partnering deal, it's shades of gray and there are pros and cons. It's a way of structuring the deal, nothing more than that," Husseini said. "We really value these companies who have this independent entrepreneurial spirit, and I've seen firsthand what happens when big companies come in and acquire these little companies."

Scientific independence is a value shared by other biotech dealmakers as well.

Gilead and Galapagos structured their $5.1 billion research deal so the smaller company would remain a motivated partner, according to Gilead CEO Daniel O'Day. Gilead also announced in May that it will keep separate its cell therapy subsidiary, Kite Pharma, which O'Day reasoned would improve efficiency.

Jeffrey Leiden, the CEO of Boston-based Vertex, told BioPharma Dive earlier this year that he planned on letting Semma Therapeutics, which Vertex had just acquired for $1 billion, operate with more autonomy because of the target company's leadership team and expertise in stem cell-derived therapies.

Follow this link:
Pharmacquired: Eylea could be in trouble, but that doesn't make Regeneron a buyer - BioPharma Dive

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Sections 4. MARKET SIZING

Sections 5. FIVE FORCES ANALYSIS

Sections 6. MARKET SEGMENTATION BY TYPE

Sections 7. CUSTOMER LANDSCAPE

Sections 8. MARKET SEGMENTATION BY PRICE

Sections 9. GEOGRAPHIC LANDSCAPE

Sections 10. Gene Therapy Market Dynamics.

Sections 11. DRIVERS AND CHALLENGES

Sections 12. MARKET TRENDS

Sections 13. VENDOR LANDSCAPE

Sections 14. VENDOR ANALYSIS

Sections 15. APPENDIX

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Global Gene Therapy Market New Innovation| Size, Share, Application, Revenue, And Sales Till 2022 - Sino News Daily

Injecting the gene-editing tool CRISPR into the brains of adolescent mice counteracts the effects of a mutation in a top autism gene. The finding suggests that mutations in this gene, SCN2A, may be treatable at any age.

This gives us hope that this is something thats not just a developmental deficit, and that once all the changes are there that youre stuck with them, says Perry Spratt, a graduate student in Kevin Benders lab at the University of California, San Francisco. Spratt presented the unpublished findings today at the 2019 Society for Neuroscience annual meeting in Chicago, Illinois.

SCN2A encodes a sodium channel that helps neurons propagate electrical signals. The mice have a harmful mutation in one copy of the gene, causing their neurons to fire sluggishly and make immature connections. The treatment reverses the problem by ramping up expression of the intact copy.

The first inkling that the reversal might work even after infancy came in June: The team reported then that introducing an SCN2A mutation into adolescent mice has many of the same effects on neurons as a mutation present from conception.

At the cellular level we see a lot of the same deficits as we see when the genes been gone throughout life, Spratt says.

The team engineered mice in which the mutation in SCN2A can be corrected by injecting an enzyme called Cre recombinase.

Running short: Neurons from mice missing SCN2A (right) have signal-receiving branches that are less mature than those in controls (left).

Injecting the Cre enzyme into the brains of 4- to 5-week-old mutant mice restored normal expression of SCN2A. It also reversed the problems in the mices neurons.

But this strategy cannot be applied to people because it would require genetic engineering of embryos. So the researchers created a virus that ferries a modified version of CRISPR into cells. This version of the editing tool does not snip DNA but can instead activate any gene.

The researchers injected the virus into the brains of 4-week-old mutant mice, along with synthetic RNA snippets designed to guide CRISPR to SCN2A. The treatment boosted SCN2A expression and reversed the problems in the mices neurons.

The team also tested one important control: They found that the treatment does not cause neurons to become hyperactive and so does not run the risk of triggering seizures.

The remarkable thing about this is that it can go gangbusters without making the cells hyperexcitable, says Bender.

The team is testing ways to deliver the virus to the whole brain. They also plan to test whether CRISPR reverses learning and memory problems in the mutant mice.

For more reports from the 2019 Society for Neuroscience annual meeting, please click here.

Read the original here:
CRISPR therapy may reverse autism mutation's effects well past infancy - Spectrum

Some gene therapies, such as bluebird bios Zynteglo, work by modifying a patients own blood stem cells to deliver a functioning gene. While they hold great potential as life-saving treatments for many immune system disorders and blood-based conditions, the process for administration can be costly and time-consuming.

In a study published in the journal Blood, scientists at Scripps Researchdescribed a possible way to more efficiently deliver genes to improve gene therapy treatment outcomesand it involves a close relative to a natural compound found in grapes.

Take Zynteglo, formerly known as LentiGlobin. Approved in the EU to treat beta thalassemia, an inherited blood disorder, it uses a lentiviral vector to insert a functioning version of the beta-globin gene into a patients blood-producing hematopoietic stem cells (HSCs) outside of the body. When the cells are given back to the patient, the gene can multiply and start to make healthy red blood cells.

Industry Insight Survey: Direct-to-Patient Distribution of Clinical Supplies

This industry survey seeks to gain insight on trial sponsors' perspective on offering a DTP option and their current level of awareness and understanding of any factors that may influence their ability to do so. The first 50 qualified respondents will receive a $5 Amazon gift card.

However, HSCs protect themselves with structures known as interferon-induced transmembrane (IFITM) proteins against viral attacks. Therefore, in preparation for a gene therapy, the lentiviral vectors could be intercepted several timeswasting a large amount of expensive materialsbefore a successful delivery.

This is why gene therapy of hemopoietic stem cells has been hit-or-miss, Bruce Torbett, the studys senior author, said in a statement. We saw a way to potentially make the treatment process significantly more efficient.

Torbett and colleagues at Scripps Research focused on caraphenol A, a small molecule related to resveratrol, which is a natural compound produced by grapes widely known for its antioxidant and anti-inflammatory effects.

The team found that adding caraphenol A to human HSCs, along with lentiviral vectors, could reduce the cells natural defenses by lowering the levels of IFITM2 and IFITM3, allowing the vectors to pass more easily. The effect was even more pronounced once the HSCs were transplanted into mice, as the cells divided and produced blood cells with the corrected gene, according to the team.

RELATED:Improving viral vectors for hemophilia gene therapies by tricking the immune system

Because gene therapy holds the promise of a potential cure for debilitating diseases that are deadly or require long-term care, scientists have been exploring new ways to improve it. A research team at the San Raffaele Telethon Institute for Gene Therapy in Italy recently found integrating the protein CD47 in the surface of lentiviral vectors could help them escape detection and destruction by the immune system once inside the body.

Torbett and his team believe caraphenol A could reduce costs of HSC-based gene therapy, which are high: Bluebird has priced Zynteglo at 1.6 million ($1.8 million) in Europe. It could also save time by helping patients get the therapy sooner. And because the longer stem cells stay outside of the body, the more likely they are to lose their ability to self-generate, more efficient gene delivery could also preserve their self-renewing properties, Tobett said.

Read more:
Could a grape-based compound improve gene therapy efficiency? - FierceBiotech

Fargo, N.D., Oct. 22, 2019 (GLOBE NEWSWIRE) -- Aldevron has announced the immediate availability of Nanoplasmids and antibiotic-free RNA-OUT technology for use in gene therapy manufacturing. Through a license agreement with Nature Technology Corporation (NTC), Aldevron can now provide its clients the option of using NTCs plasmid technology to provide a more efficient system for manufacturing viral vectors used in gene and cell therapy. Gene and cell therapy companies interested in using NTCs technology can now go directly to Aldevron for their manufacturing needs without first obtaining a license from NTC. For applications where the NTC plasmid is not the active pharmaceutical ingredient or in the final product clients do not need to pay any royalties or license fees beyond the purchase price of the product.

Gene and cell therapy researchers continue to make incredible discoveries that will improve lives for millions of people, said Michael Chambers, Aldevron CEO. Aldevron is committed to providing the best manufacturing technologies to support their breakthrough treatments. Our partnership with NTC enables us to provide plasmid technology that significantly improves the manufacturing process and reduces regulatory risk, resulting in reduced costs and faster time to patients.

The fields of gene and cell therapy are surging with the approvals of Kymriah and Yescarta CAR-T treatments for cancer and Luxturna for the treatment of Leber congenital amaurosis, a rare genetic ocular disease. With nearly 3,000 clinical trials underway, improvements in manufacturing are required to provide the capacity to accommodate the growth in research and anticipated commercial products. The NTC technology, combined with Aldevrons unequaled scale and throughput, assure clients will have the products they need.

Our Nanoplasmid and RNA-OUT technology has been under development for 12 years and can provide demonstrable advantages for viral vector manufacturing, said Clague Hodgson, CEO of NTC. We are pleased to collaborate with Aldevron to make this technology immediately available to its clients so they can avoid the delay and expense associated with the licensing process thereby reducing the barriers to delivering transformative treatments to patients.

Providing these novel plasmids furthers our strategy to go beyond the traditional role of a contract development and manufacturing organization, added Chambers. Aldevron provides a variety of options for clients, including off-the-shelf, royalty-free helper plasmids for AAV production and packaging plasmids for lentiviral production, in pursuit of our goal to enable our clients to make a difference in the lives of the patients they serve. For more information on Nanoplasmids, please visitaldevron.com/nanoplasmid.

About Aldevron

Aldevron serves the biotechnology industry with custom production of nucleic acids, proteins, and antibodies. Thousands of clients use Aldevron-produced plasmids, RNA and gene editing enzymes for projects ranging from discovery research to clinical trials to commercial applications. These products are critical raw materials and key components in commercially available drugs and medical devices. Aldevron specializes in GMP manufacturing and is known for inventing the GMP-Source quality system. Company headquarters are in Fargo, North Dakota, with additional facilities in Madison, Wisconsin, and Freiburg, Germany. To learn more, visitwww.aldevron.com.

About Nature Technology Corporation

Nature Technology Corporation is a developer of safe and effective nucleic acid-based gene therapeutics, DNA vaccines, and associated technologies, including antibiotic-free selection (RNA-OUT), regulatory compliance, viral vector retrofitting, and best in class NanoplasmidsTM. NTC proprietary vector and manufacturing platforms offer wide applications to improve the safety and performance of plasmids and biologics. NTC also provides cost effective outsourcing of product development services including custom gene design, vector construction, plasmid DNA manufacturing and recombinant proteins. For more information about NTC products and business related inquiries visitwww.natx.comor contact Deborah Moorad-Watts, email: dmoorad@natx.com.

Original post:
Aldevron, Nature Technology Corporation team up to offer Nanoplasmids for gene therapy manufacturing - GlobeNewswire

In order to help individuals suffering from emotion dysregulation, Stanford Psychophysiology Laboratorys Wehab Lab has developed a haptic breathing pacer (HBP) prototype. The technology also helps those diagnosed with Autism Spectrum Disorder better regulate anxiety levels. (Photo : Pardis Miri)

The Wehab Lab of the Stanford Psychophysiology Laboratory has been working on developing a haptic breathing pacer (HBP) to address issues surrounding mental health and emotion dysregulation, an individuals inability to change an undesired emotional experience. The device applies vibrations to a users body, with which they can synchronize their breathing to reduce arousal in high-stress situations.

Post-graduate researcher Pardis Miri described it as important for helping individuals cope with a stressor.

There is significant recent interest in developing technology that can help people regulate high-arousal negative affect in the course of their everyday lives, she wrote. Negative affect is a personality trait that includes emotions such as anger, anxiety and stress. These technologies have all been designed for a neurotypical population and, for the most part, [are] not well-evaluated for efficacy. The term neurotypical refers to individuals without a developmental disorder.

Technologies being developed by other researchers are not evaluated with consideration for those with individual differences or the neurodiverse population, according to Miri. But Miris team found that their inconspicuous and personalizable breathing pacer prototype could be able to help individuals outside of the neurotypical population, she said.

The prototype proved to be especially promising, Miri wrote, for individuals who score low in terms of two traits: openness, as measured by the Big Five scale, and usage of reappraisal, a psychological strategy that lessens the emotional impact of a stressful event.

These are characteristics commonly observed in Autism Spectrum Disorder (ASD) population, and so our findings suggest potential interventional success for individuals diagnosed with ASD, Miri said.

Helping these children successfully regulate their affect could have a major impact on their development and could prevent them from serious health issues, Miri wrote.

Horia Margarit M.S. 17, a member of the research team, used machine-learning techniques to analyze data collected from the prototypes.

He used a method published in 2017, he said. Very few people even know about it, and thats one of the major triumphs of our research because we were able to show this level of success using that technique.

The team is focusing on improving the efficacy of their pacer for individuals with ASD.

We believe our approach is promising for individuals diagnosed with ASD, and we also understand the risks that are involved, Miri wrote. Our goal is to create a personalizable vibrotactile system that utilizes the strengths of the autistic population to respond to their affect regulatory needs.

Miri said her aim is to demonstrate the efficacy of her teams approach in regulating the affect that individuals diagnosed with ASD experience in their daily lives.

This is tremendously promising research because the entire concept behind this is similar to that of CRISPR and gene therapy: personalized medicine, Margarit said. What Pardis and I did was understanding people on a personal level in terms of mental health.

Contact Camryn Pak at cpak23 at stanford.edu.

We're a student-run organization committed to providing hands-on experience in journalism, digital media and business for the next generation of reporters.Your support makes a difference in helping give staff members from all backgrounds the opportunity to develop important professional skills and conduct meaningful reporting. All contributions are tax-deductible.

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Researchers work on device to help individuals cope with autism - The Stanford Daily

NEW YORK, Oct. 21, 2019 /PRNewswire/ --

Personalized Medicine Market Size, Share & Trends Analysis By Product (Personalized Medical Care, Therapeutics, Personalized Nutrition & Wellness), By Region (Asia Pacific, Europe, North America), And Segment Forecasts, 2019 - 2025

Read the full report: https://www.reportlinker.com/p05807253/?utm_source=PRN

The global personalized medicine (PM) market size is expected to reach USD 3.18 trillion by 2025 registering a CAGR of 10.6% over the forecast period. Growing number of approved companion diagnostics and biomarker products have been proved promising avenues for the development of advanced precision diagnostic tests. Several personalized diagnostics and therapeutic products based on companion diagnostics are under clinical trials and development pipelines, which also add an incremental opportunity to accelerate this market.

Gene therapies are widely utilized to diagnose both chronic and genetic disorders according to individual's genetic makeup.Growing adoption of gene sequencing and data analytics technologies is anticipated to escalate precision medicine market growth.

Decreasing cost of whole genome sequencing, advancement in cell biology sector, and the development of "Human Genome Project" are several other factors influencing the demand for gene therapy hence, boosting the overall market. Moreover, key leaders are undergoing numerous strategic developments to launch novel personalized products, which will also contribute to the market expansion.

For instance, in September 2018, Vertex Pharmaceuticals collaborated with Genomics for the delivery of precision medicine based on individual's genetic differences and lifestyle. Similarly, in January 2018, Foundation Medicine collaborated with European Organization for Research and Treatment of Cancer (EORTC) to facilitate Foundation's comprehensive genomic profiling to across personalized medicine and clinical trial enrolment.

Further key findings from the study suggest: PM therapeutics is projected to register the fastest CAGR over the forecast period owing to the development of high-capacity rapid sequencing platforms for medical therapies Reduction in sequencing cost leads to an expected growth of genomic sequencing and genetic research, thus contributing to lucrative opportunities for genomic medicine Asia Pacific is projected to be the fastest-growing regional market due to rising number of collaborative initiatives between eastern and western market leaders Chinese personalized medicine market is benefitted due to initiatives implemented by the Chinese government and reimbursements for disease treatment Prominent companies include GE Healthcare; Illumina, Inc.; Asuragen, Inc.; Abbott Laboratories; Dako A/S; Exact Science Corp.; and Biogen, Inc.

Read the full report: https://www.reportlinker.com/p05807253/?utm_source=PRN

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View original content:http://www.prnewswire.com/news-releases/the-global-personalized-medicine-pm-market-size-is-expected-to-reach-usd-3-18-trillion-by-2025-registering-a-cagr-of-10-6-over-the-forecast-period-300941893.html

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The global personalized medicine (PM) market size is expected to reach USD 3.18 trillion by 2025 registering a CAGR of 10.6% over the forecast period...

LONDON--(BUSINESS WIRE)--

The market will accelerate at a CAGR of over 8% between 2019-2023

The report, global age-related macular degeneration (AMD) therapeutics market has been added to Technavios catalog. It provides a comprehensive analysis of the market, including its global and regional market share as well as market segmentation based on type and geography for the forecast period 2019-2023.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20191021005715/en/

To learn more about the global trends impacting the future of market research: Download Free Sample Report

This report on the age-related macular degeneration (AMD) therapeutics market includes:

Age-related macular degeneration (AMD) therapeutics market analysis and forecast 2019-2023: Features

Competitive landscape

Market segmentation

Type

Geography

Market drivers

Market trends

Market challenges

Five forces analysis

Market landscape

Market sizing & forecast

Age-Related Macular Degeneration (AMD) Therapeutics Market 2019-2023: Competitive Landscape

Vendors covered

Vendor classification

Amgen Inc.

Bausch Health Companies, Inc.

F. Hoffmann-La Roche Ltd.

Novartis AG

Regeneron Pharmaceuticals Inc.

Age-Related Macular Degeneration (AMD) Therapeutics Market 2019-2023: Geographic Landscape

North America - Market size and forecast 2018-2023

Europe - Market size and forecast 2018-2023

Asia - Market size and forecast 2018-2023

ROW - Market size and forecast 2018-2023

Key leading countries

Age-Related Macular Degeneration (AMD) Therapeutics Market 2019-2023: Type Landscape

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High prevalence of AMD will drive the age-related macular degeneration (AMD) therapeutics market

The prevalence of AMD is increasing significantly, owing to the presence of high-risk factors such as aging, smoking, high cholesterol, and high blood pressure. Moreover, despite the high prevalence of AMD, no approved therapies are available in the market for the treatment of the condition. Thus, the high prevalence coupled with the huge unmet medical need of dry AMD are expected to drive market growth during the forecast period.

Story continues

Development of gene therapy for AMD An emerging trend in the osteoporosis market

At present, only a few drugs are approved for the treatment of AMD. However, the side effects associated with them are very severe, and the majority of them act against VEGF only. Hence, there is a huge unmet need for safe and novel drugs to treat AMD. The currently available anti-VEGF therapies require repetitive and inconvenient intraocular injections. Hence, several companies are working on novel drugs to combat AMD, among which gene therapy is expected to cure the disease effectively. Hence, the development of gene therapy is expected to be a positive trend for the global AMD therapeutics market.

Other Key Topics Covered in the Report are:

MARKET LANDSCAPE

MARKET SIZING

Get Full Report: https://www.technavio.com/report/age-related-macular-degeneration-therapeutics-market-industry-analysis

CUSTOMER LANDSCAPE

DECISION FRAMEWORK

DRIVERS AND CHALLENGES

Market drivers

Market challenges

Market Trends

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Growth of Age-Related Macular Degeneration (AMD) Therapeutics Market to be Impacted by the Development of Gene Therapy for AMD | Technavio - Yahoo...

ImmuneCyte to Begin Operations in Fourth Quarter of 2019

RANCHO CORDOVA, Calif., Oct. 22, 2019 /PRNewswire/ -- Cesca Therapeutics Inc. (Nasdaq: KOOL), a market leader in automated cell processing and autologous cell therapies for regenerative medicine, and ThermoGenesis, its wholly owned device subsidiary, today announced that the company has entered into a definitive joint venture agreement with HealthBanks Biotech (USA) Inc., one of the world's leading stem cell bank networks, to commercialize its proprietary cell processing platform, CAR-TXpress, for use in immune cell banking as well as for cell-based contract development and manufacturing services (CMO/CDMO). The joint venture will be named ImmuneCyte Life Sciences Inc. ("ImmuneCyte") and is expected to officially launch during the fourth quarter of 2019.

Under terms of the agreement, ImmuneCyte will initially be owned 80% by HealthBanks Biotech and 20% by Cesca. Cesca will contribute to ImmuneCyte exclusive rights to use ThermoGenesis' proprietary cell processing technology for the immune cell banking business and non-exclusive rights for other cell-based contract development and manufacturing services. Cesca will also contribute its clinical development assets to the joint venture, as the company has decided to discontinue these activities in order to focus exclusively on the device business.

Once operational, ImmuneCyte will be among the first immune cell banks in the U.S. to provide clients with the opportunity to bank their own healthy immune cells for future use as a resource for cell-based immunotherapies, such as dendritic cell and chimeric antigen receptor (CAR) T-cell therapies. ImmuneCyte will utilize ThermoGenesis' proprietary CAR-TXpress platform which allows for the isolation of different components from 200 ml of blood in cGMP compliant, closed system. Given that the CAR-TXpress platform can increase cell processing efficiency by up to 16-fold as compared with the traditional, labor-intensive ficoll gradient centrifugation-based cell processing method, ImmuneCyte is expected to offer customers an unparalleled competitive advantage, including an ability to store their own immune cells at a tangibly lower cost.

"The ImmuneCyte joint venture will be paramount to the execution of our strategy to become a preferred cell processing and manufacturing solution provider in the cell and gene therapy field," said Dr. Chris Xu, Chairman and Chief Executive Officer of Cesca Therapeutics. "CAR-T therapeutic research is advancing rapidly. Partnering with HealthBanks Biotech, one of the foremost stem cell bank networks, with an experienced team and an established global infrastructure, will offer customers the ability to preserve younger, healthier and uncontaminated immune cells for potential future use. By applying our proprietary CAR-TXpress technology to immune cell banking and other CDMO cellular manufacturing services, we will allow for the manufacture and production of more effective and less costly immunotherapies."

In 2017, the U.S. Food and Drug Administration (FDA) approved two CAR-T cell therapies, under breakthrough designation, for the treatment of advanced B cell leukemia and lymphomas. Both use autologous (a patient's own) immune T cells to fight cancer and have reported an over 80% response rate in the "no-option" patient group, for those who have failed both chemo- and radiation therapies. This has helped to spur massive global interest for the development of additional CAR-T immunotherapies1. By the end of September 2019, there were over 800 CAR-T cell clinical trials registered on the http://www.clinicaltrials.gov website, targeting a wide variety of blood cancers and solid tumors.

Although highly effective, several recent studies on the eligibility of patients to enroll in CAR-T clinical trials showed that as many as 30-50% of cancer patients may not be eligible to enroll or to get sufficient CAR-T cells manufactured for the therapy. Reasons may include: (1) the function of the immune system declines with age and can be negatively affected by other medical conditions, (2) most standard cancer therapies, such as chemotherapy and radiation, destroy the immune system, and (3) in many cases of advanced cancer, cancer cells will enter circulation, invade and interfere with the body's natural production of immune cells. According to a recently reported JULIE trial, a CAR-T clinical trial in relapsed or refractory diffuse large B-cell lymphoma (DLBCL), one-third of the 238 screened patients failed to be enrolled, and more than half of the 238 failed to receive the intended CAR-T therapy2,3. ImmuneCyte will offer customers the ability to preserve younger, healthier and uncontaminated immune cells, for potential future use in advanced cancer immunotherapy.

About HealthBanks Biotech (USA) Inc.HealthBanks Biotech, headquartered in Irvine, CA, is one of the leading stem cell bank networks in the world and offers services globally through its sister companies located in the United States and other regions and nations. HealthBanks Biotech is accredited by the FDA, AABB, and CAP. The HealthBanks Biotech group was originally founded in 2001 with a vision that stem cells and cell and gene therapies could transform modern medicine. HealthBanks Biotech is a subsidiary of Boyalife Group, Inc. (USA), an affiliate of Boyalife (Hong Kong) Limited, the largest stockholder of Cesca. For more information about HealthBanks Biotech (USA) Inc., please visit: http://www.healthbanks.us.

About ImmuneCyte Life Sciences Inc.ImmuneCyte will provide clients with the opportunity to bank their own immune cells when the cells are "healthy and unaffected" as a future resource for cellular immunotherapies, such as CAR-T. ImmuneCyte utilizes a proprietary CAR-TXpress platform, a GMP compliant close-system capable of automated separating and cryopreserving different components from blood. For more information about ImmuneCyte Life Sciences Inc., please visit: http://www.immunecyte.com.

About Cesca Therapeutics Inc.Cesca Therapeutics develops, commercializes and markets a range of automated technologies for CAR-T and other cell-based therapies. Its device division, ThermoGenesis develops, commercializes and markets a full suite of solutions for automated clinical biobanking, point-of-care applications, and automation for immuno-oncology. The Company has developed a semi- automated, functionally closed CAR-TXpress platform to streamline the manufacturing process for the emerging CAR-T immunotherapy market. For more information about Cesca and ThermoGenesis, please visit: http://www.cescatherapeutics.com.

Company Contact:Wendy Samford916-858-5191ir@thermogenesis.com

Investor Contact:Paula Schwartz, Rx Communications917-322-2216pschwartz@rxir.com

References:

1. Facts About Chimeric Antigen Receptor (CAR) T-Cell Therapy, Leukemia and Lymphoma Society (2018). https://www.lls.org

2. Updated Analysis of JULIET Trial: Tisagenlecleucel in Relapsed or Refractory DLBCL (2018).

3. Eligibility Criteria for CAR-T Trials and Survival Rates in Chemorefractory DLBCL. Journal of Clinical Pathways (2018).

View original content:http://www.prnewswire.com/news-releases/cesca-therapeutics-forms-joint-venture-with-healthbanks-biotech-usa-to-provide-immune-cell-banking-and-cell-processing-services-300942618.html

SOURCE Cesca Therapeutics Inc.

Company Codes: NASDAQ-SMALL:KOOL

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Cesca Therapeutics Forms Joint Venture with Healthbanks Biotech (USA) to Provide Immune Cell Banking and Cell Processing Services - BioSpace

PARIS--(BUSINESS WIRE)--Regulatory News:

GenSight Biologics (Paris:SIGHT)(Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today reported its cash position as of September 30, 2019, and provided recent operational updates.

Cash and cash equivalents

GenSight Biologics cash and cash equivalents totaled 5.1 million as of September 30, 2019, compared to 14.3 million as of June 30, 2019. This amount does not include a 4.3 million reimbursement of the 2018 Research Tax Credit, expected in the coming days. Including this impending reimbursement, cash and cash equivalents would be 9.4 million as of September 30, 2019.

The cash burn in the first three quarters of 2019 principally reflects the final steps of pharmaceutical development for GS010 in preparation for a marketing authorization filing in Europe. These are mainly preparatory activities to ensure manufacturing readiness to commercialize under Good Manufacturing Practices (GMP).

In line with our expectations and including the impending reimbursement of the 2018 Research Tax Credit, we are fully financed until the end of the first quarter of 2020, commented Thomas Gidoin, Chief Financial Officer of GenSight Biologics. We have been actively working on a financing transaction in the past weeks, favoring less dilutive options, and expect to be able to announce a closing shortly.

Clinical Development of GS010

Results at 96 weeks of the RESCUE Phase III clinical trial evaluating the efficacy and safety of a single intravitreal injection of GS010 in subjects with LHON due to the ND4 mutation with an onset of vision loss up to 6 months were reported in September 2019. This last set of results showed a durable bilateral improvement in visual acuity of 25 ETDRS letters equivalent versus nadir in GS010-treated eyes. These results from RESCUE show a remarkable correspondence with those from the REVERSE trial, which studied the treatment of subjects at 6 to 12 months after onset of vision loss.

In a natural history study conducted by Santhera1, 28% of subjects with the G11778A-ND4 mutation achieved a spontaneous clinically relevant recovery (CRR) from nadir in at least one eye. By comparison, 63% of RESCUE subjects achieved this definition of CRR in at least one eye at Week 96, showing a clear superiority to natural history. A similar comparison for REVERSE subjects reveals a much higher rate of CRR (78%) from nadir compared to natural history.

GenSight also reported results from a non-clinical study to investigate the local biodistribution of GS010. In this study, tissue samples from the non-injected eye of monkeys that had been unilaterally injected with GS010 were found to contain GS010 DNA three months after injection, indicating the expression of the therapeutic gene in the uninjected contralateral eye. These findings support the mechanism for bilateral visual improvement with unilateral GS010 gene therapy, which was consistently observed in LHON subjects in the REVERSE and RESCUE Phase III trials.

Regulatory Pathway of GS010

GenSight is planning to schedule a pre-submission meeting with the EMA in early 2020 and expects to submit an application for marketing approval in Europe in the third quarter of 2020.

An End of Phase II meeting with the U.S. Food and Drug Administration (FDA) was requested as planned, which the agency has now confirmed for December 19, 2019.

We strongly believe that the remarkable results from REVERSE and RESCUE, showing a clinically significant and durable bilateral improvement of vision, and demonstrating clear superiority to natural history, are a compelling core for our marketing authorization application in Europe, commented Bernard Gilly, co-founder and Chief Executive Officer of GenSight Biologics. The demonstration of GS010 DNA presence in the uninjected contralateral eye now provides a powerful scientific rationale to support bilateral improvement. We are eager to meet with regulatory agencies in the next few weeks to discuss these major findings.

Number of outstanding shares

As of September 30, 2019, GenSight Biologics number of outstanding shares was 29,028,291 ordinary shares.

GenSight Biologics will report its cash position as of December 31, 2019 on January 21, 2020.

GenSight will host a conference call today, October 22, 2019, at 9:30am CEST in French, and at 2.30pm CEST (8.30am EST) in English, to further discuss this operational update.

Conference call in French

Dial-in numbers:

France: +33 (0) 1 7037 7166Password: GenSight Franais

Conference call in English

Dial-in numbers:

United States: +1 212 999 6659France: +33 (0) 1 7037 7166United Kingdom: +44 (0) 20 3003 2666Password: GenSight English

A replay of the calls will be available using the following dial-in numbers:

France: +33 (0) 1 7037 7166United Kingdom (standard international access): +44 (0) 20 3003 2666Code: 5645038#

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics lead product candidate, GS010, is in Phase III trials in Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease that leads to irreversible blindness in teens and young adults. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery.

1 Magda et al (2019), Natural History of Lebers Hereditary Optic Neuropathy (LHON): Findings from a Large Patient Cohort, Poster presented at NANOS March 16-21, 2019; Poster Session II: Scientific Advancements; Poster: 163

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GenSight Biologics Reports its Cash Position as of September 30, 2019 and Provides Operational Update - Business Wire

NEW YORK and CLEVELAND, Oct. 21, 2019 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq: ABEO), a fully-integrated leader in gene and cell therapy, today announced the presentations of data from the Transpher A Study, the Companys ongoing Phase 1/2 clinical trial evaluating ABO-102 for the treatment of Sanfilippo syndrome type A (MPS IIIA), and research updates from its library of novel AIMTM adeno-associated virus (AAV) capsids at the 27th European Society of Gene and Cell Therapy (ESGCT) Congress, to be held October 22-25, 2019 in Barcelona, Spain.

The data will be presented as follows:

Safety, Tolerability, Biopotency and Neurocognitive Data of ABO-102 in Transpher A, an Open-Label, Multicenter, Single-Dose, Dose-Escalation, Phase 1/2 Clinical Trial in Sanfilippo Syndrome type A (Mucopolysaccharidosis IIIA)Oral Presentation #039Presenter: Maria Jose de Castro, M.D., Hospital Universitario Santiago de CompostelaSession 4c: Metabolic and Genetic DiseasesDate/Time: Friday, October 25, 2019, 9:00 a.m. to 11:00 a.m. CESTLocation: Room 112

Novel AAV Capsids Show Increased Evasion to Neutralizing Antibodies Against Natural SerotypesPoster #P347Session Title: Poster Session IDate/Time: Wednesday, October 23, 2019, 1:00 p.m. to 3:00 p.m. CESTLocation: Multipurpose Hall

Development of an Improved Novel AAV Capsids for Intramuscular DeliveryPoster #P027Session Title: Poster Session IDate/Time: Wednesday, October 23, 2019, 1:00 p.m. to 3:00 p.m. CESTLocation: Multipurpose Hall

Novel AAV Capsids for Delivery to the Retina by Intravitreal AdministrationPoster #P009Session Title: Poster Session IDate/Time: Wednesday, October 23, 2019, 1:00 p.m. to 3:00 p.m. CESTLocation: Multipurpose Hall

Development of a Novel AAV Capsid with Improved PNS Tropism for Treating Pompe Disease by Intravenous AdministrationPoster #P007Session Title: Poster Session IDate/Time: Wednesday, October 23, 2019, 1:00 p.m. to 3:00 p.m. CESTLocation: Multipurpose Hall

About Abeona Therapeutics Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene and cell therapies for serious diseases. The Companys clinical programs include EB-101, its autologous, gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa, as well as ABO-102 and ABO-101, novel AAV9-based gene therapies for Sanfilippo syndrome types A and B (MPS IIIA and MPS IIIB), respectively. The Companys portfolio of AAV9-based gene therapies also features ABO-202 and ABO-201 for CLN1 disease and CLN3 disease, respectively. Its preclinical assets include ABO-401, which uses the novel AIM AAV vector platform to address all mutations of cystic fibrosis. Abeona has received twenty regulatory designations from the FDA and EMA for its pipeline candidates. For more information, visit http://www.abeonatherapeutics.com.

Forward-Looking StatementsThis press release contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties. These statements include statements about the Companys clinical trials and its products and product candidates, future regulatory interactions with regulatory authorities, as well as the Companys goals and objectives. We have attempted to identify forward looking statements by such terminology as may, will, believe, estimate, expect, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances), which constitute and are intended to identify forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, numerous risks and uncertainties, including but not limited to continued interest in our rare disease portfolio, our ability to enroll patients in clinical trials, the outcome of any future meetings with the U.S. Food and Drug Administration or other regulatory agencies, the impact of competition, the ability to secure licenses for any technology that may be necessary to commercialize our products, the ability to achieve or obtain necessary regulatory approvals, the impact of changes in the financial markets and global economic conditions, risks associated with data analysis and reporting, and other risks as may be detailed from time to time in the Companys Annual Reports on Form 10-K and quarterly reports on Form 10-Q and other periodic reports filed by the Company with the Securities and Exchange Commission. The Company undertakes no obligation to revise the forward-looking statements or to update them to reflect events or circumstances occurring after the date of this presentation, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.

Investor Contact:Sofia WarnerSenior Director, Investor RelationsAbeona Therapeutics+1 (646) 813-4710swarner@abeonatherapeutics.com

Media Contact:Scott SantiamoDirector, Corporate CommunicationsAbeona Therapeutics+1 (718) 344-5843ssantiamo@abeonatherapeutics.com

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Abeona Therapeutics Announces Presentations at the 27th European Society of Gene and Cell Therapy (ESGCT) Congress - BioSpace

CAMBRIDGE, Mass., Oct. 21, 2019 /PRNewswire/ -- SmartPharm Therapeutics, a preclinical-stage pharmaceutical company focused on developing next-generation, non-viral gene therapies for the treatment of rare diseases, today announced the appointment of John T. Potts, MD, DSc, to its Board of Directors. Dr. Potts' distinguished, five-decade career in healthcare and the life sciences spans medical disciplines and encompasses ground-breaking preclinical and clinical research.

"We are honored to welcome John to the SmartPharm Board. His acumen and experience will be invaluable to the Company during its journey into the clinic," said Steve Gorlin, Chairman of the Board for SmartPharm.

"I am excited to be joining SmartPharm Therapeutics and believe the Company's approach to next-generation, non-viral, gene-encoded protein therapies holds significant potential to impact medicine in a similar manner to biologics, while eliminating their onerous manufacturing and delivery systems," commented Dr. Potts.

Dr. Potts is the Jackson Distinguished Professor of Clinical Medicine at the Massachusetts General Hospital (MGH) and Harvard Medical School. After completing his MD at the University of Pennsylvania and internship and residency at MGH, he worked at the National Institutes of Health for almost a decade, studying protein chemistry with Nobel laureate Christian Anfinsen. He returned to MGH as Chief of Endocrinology in 1968 where he subsequently served as Director of Research, Chairman of the Department of Medicine and Physician-in-Chief. An internationally-recognized authority on calcium metabolism and the hormonal mechanisms that govern it, he has been a pioneer in identifying the chemistry and biology of clinical disorders of bone and mineral ion metabolism.

Dr. Potts has played an active role in the life sciences industry. He is a founder of Radius Health, Inc., a biopharmaceutical company focused on developing and commercializing innovative endocrine therapeutics in the areas of osteoporosis and oncology, where he currently serves as a Scientific Advisory Board Member. He has also served on advisory boards with MPM Capital and HealthCare Ventures. He has previously held board of directors positions with Cell Genesys, Zeltiq Aesthetics, Genentech and NantKwest.

An author on over 500 publications, his honors and awards include the Association of Professors of Medicine's Robert H. Williams, MD, Distinguished Chair of Medicine Award; the Biomedical Science Career Program Hope Award; the Endocrine Society's Fred Konrad Koch Award; and the American Society for Bone and Mineral Research's William F. Neumann Award. He holds active and honorary memberships in a number of scientific and professional organizations including the National Academy of Medicine, American Academy of Arts and Sciences, and the National Academy of Sciences.

About SmartPharm Therapeutics

SmartPharm Therapeutics Inc. is a privately-held, development-stage pharmaceutical company focused on developing next-generation, non-viral gene therapies for the treatment of serious or rare diseases with the vision of creating "biologics from within." The Company is currently developing a novel pipeline of non-viral, gene-encoded proteins for the treatment of conditions that require enzyme replacement therapy and tissue restoration. SmartPharm commenced operations in 2018 and is headquartered in Cambridge, MA, USA. For more information, please visit http://www.smartpharmtx.com.

View original content:http://www.prnewswire.com/news-releases/smartpharm-therapeutics-appoints-john-t-potts-md-dsc-to-board-of-directors-300941723.html

SOURCE SmartPharm Therapeutics

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SmartPharm Therapeutics Appoints John T. Potts, MD, DSc, to Board of Directors - BioSpace

Vancouver, Canada, October 21, 2019 ISCT, the International Society for Cell and Gene Therapy, the global professional society of clinicians, researchers, regulatory specialists, technologists and industry partners in the cell and gene therapy sector, today announces it has formed a global consortium of a wide range of leading professional and education societies to combat the rise in the number of unproven commercial cell banking services. Full details of the statement can be foundhere.

The consortium partners include the International Society for Stem Cell Research (ISSCR), Society for Immunotherapy of Cancer (SITC), American Society for Transplantation and Cellular Therapy (ASTCT),American Society of Gene & Cell Therapy (ASGCT), European Society for Blood and Marrow Transplantation (EBMT), Foundation for the Accreditation of Cellular Therapy (FACT), Joint Accreditation Committee ISCT-EBMT (JACIE) and the Forum for Innovative Regenerative Medicine (FIRM).

The consortium has been formed following ISCT issuingpatient advice and concern on unproven T-cell preservation services on August 7, 2019. These services include the banking of T-cells, dental cells and cells for the derivation of induced pluripotent stem cells for potential therapeutic uses.

The joint statement from ISCT and the consortium partners includes an agreement on a number of key points. Commercial cell banking services are not supported by current scientific evidence, as opposed to the range of cell therapies such as CAR-T therapies, that follow established approval processes. Additionally, cell banking services cannot claim to know that the cells they preserve today could ever be appropriate for clinical use, could be used by manufacturers, or meet the requirements of many national and international regulatory agencies. As a result, there is no clear pathway to legitimate clinical use. All parties agree offering these services commercially to patients is thus premature, misleading, and drives false hope.

In addition, the ISCT joint statement makes clear that patients, being misled by these services, are thus prevented from giving a full and valid informed consent. Cell banking companies mislead patients in a number of ways, including using tokens of scientific legitimacy that suggest a stronger scientific basis than currently exists. These tokens include endorsements from individuals or scientific advisory boards that might not fully endorse the specific products, links to scientific articles, and references to ongoing clinical trials.

ISCTs raison detre is to lead the industry in supporting scientifically validated cell and gene therapies. As a result, ISCT will continue to welcome all innovations, including cell banking approaches, that increase the number of patients who can benefit from these therapies, said Bruce Levine,President-Elect, ISCT and one of the inventors of CAR-T therapies.However, ISCT also leads industry action on unproven cell therapies and services in the cell and gene sector. This is why ISCT has forged a consortium throughout the industry against the marketing of speculative cell banking services that do not have appropriate pre-clinical, and clinical evidence and a plausible pathway to the clinical use of banked cells. We collectively believe these banks have the potential to be detrimental to the future development of cell and gene therapies.

About ISCT

Established in 1992, ISCT, the International Society for Cell and Gene Therapy is a global society of clinicians, regulators, researchers, technologists and industry partners with a shared vision to translate cellular therapy into safe and effective therapies to improve patients lives worldwide.

ISCT is the global leader focused on pre-clinical and translational aspects of developing cell-based therapeutics, thereby advancing scientific research into innovative treatments for patients. ISCT offers a unique collaborative environment that addresses three key areas of translation: Academia, Regulatory and Commercialization. Through strong relationships with global regulatory agencies, academic institutions and industry partners, ISCT drives the advancement of research into standard of care.

Comprised of over 1,500 cell therapy experts across five geographic regions and representation from over 50 countries, ISCT members are part of a global community of peers, thought leaders and organizations invested in cell therapy translation. For more information about the society, key initiatives and upcoming meetings, please visit:

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ISCT forms cell and gene therapy sector-wide coalition to combat the rise of unproven commercial cell banking services - PharmiWeb.com

Tay-Sachs Disease Pipeline Insight Market Research 2019 report by Mart Research outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Tay-Sachs Disease pipeline landscape is provided which includes the disease overview and Tay-Sachs Disease treatment guidelines. The assessment part of the report embraces, in depth Tay-Sachs Disease commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Tay-Sachs Disease collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Tay-Sachs Disease Understanding

According to National Organization for Rare Disorders (NORD), Tay-Sachs disease is a rare, neurodegenerative disorder in which deficiency of an enzyme hexosaminidase A results in excessive accumulation of certain fats (lipids) known as gangliosides in the brain and nerve cells. This abnormal accumulation of gangliosides leads to progressive dysfunction of the central nervous system. This disorder is categorized as a lysosomal storage disease. Tay-Sachs disease is broken down into the classic or infantile form, the juvenile form, and the adult or late-onset form. In individuals with infantile Tay-Sachs disease, symptoms typically first appear between three and five months of age. In individuals with the late-onset form, symptoms may become apparent anytime from adolescence through the mid-30s.

Browse Full Tay-Sachs Disease Pipeline Insight Market Research Report @ https://martresearch.com/market-analysis/tay-sachs-disease-pipeline-insight/2/42159

Companies Covered in Tay-Sachs Disease Pipeline Insight Mart ResearchAxovant Gene TherapiesIntraBioActelion PharmaceuticalsCastle Creek PharmaceuticalsAvigenGene Therapy Research InstitutionOxford Glycobiology InstituteAmicus TherapeuticsAldagenRecursion Pharmaceuticals

Drugs Covered in Tay-Sachs Disease Pipeline Insight Market Research Report:AXO AAV GM2N-Acetyl-L-LeucineMiglustatCCP 010Lysosomal storage disease gene therapyResearch programme: Tay-Sachs disease gene therapyAcetylleucineResearch programme: calcium channel modulatorsCDP 923Research programme: Lysosomal storage disorder therapeuticsALD 601Research programme: rare genetic disorder therapeutics

r is categorized as a lysosomal storage disease. Tay-Sachs disease is broken down into the classic or infantile form, the juvenile form, and the adult or late-onset form. In individuals with infantile Tay-Sachs disease, symptoms typically first appear between three and five months of age. In individuals with the late-onset form, symptoms may become apparent anytime from adolescence through the mid-30s.

Companies Covered in Tay-Sachs Disease Pipeline Insight Market Research Report:

Axovant Gene Therapies

IntraBio

Actelion Pharmaceuticals

Castle Creek Pharmaceuticals

Avigen

Gene Therapy Research Institution

Oxford Glycobiology Institute

Amicus Therapeutics

Aldagen

Recursion Pharmaceuticals

Drugs Covered in Tay-Sachs Disease Pipeline Insight Market Research Report:

AXO AAV GM2

N-Acetyl-L-Leucine

Miglustat

CCP 010

Lysosomal storage disease gene therapy

Research programme: Tay-Sachs disease gene therapy

Acetylleucine

Research programme: calcium channel modulators

CDP 923

Research programme: Lysosomal storage disorder therapeutics

ALD 601

Research programme: rare genetic disorder therapeutics

Tay Sachs disease Pipeline Development Activities

The report provides insights into different therapeutic candidates in discovery and preclinical, phase 1, phase 2, and phase 3 stage. Drugs under development as a monotherapy or combination therapy are also included. It also analyses key players involved in Tay Sachs disease targeted therapeutics development with respective active and inactive (dormant or discontinued) projects with the appropriate reasons if available. Tay Sachs disease pipeline report covers 6+ companies. Some of the key players include IntraBio Inc (IB1001-201), Castle Creek Pharmaceuticals (CCP 010) etc.

The report is built using data and information traced from the researchers proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university web sites and industry-specific third party sources, etc.

Tay Sachs disease Analytical Perspective by Mart Research

In-depth Tay-Sachs Disease Commercial Assessment of products

This report provides an in-depth Commercial Assessment of therapeutic drugs have been included which comprises of collaborations, Licensing, Acquisition Deal Value Trends. The sub-segmentation is described in the report which includes Company-Company Collaborations (Licensing / Partnering), Company-Academia Collaborations, and Acquisition analysis in both Graphical and tabulated form.

Tay-Sachs Disease Clinical Assessment of products

The report comprises of comparative clinical assessment of products by development stage, product type, route of administration, molecule type, and MOA type across this indication.

To Buy Tay-Sachs Disease Pipeline Insight Market Research Report @ https://martresearch.com/paymentform/2/42159/Single_User

Scope of the report

The Tay Sachs disease report provides an overview of therapeutic pipeline activity for Tay Sachs disease across the complete product development cycle including all clinical and non-clinical stages

It comprises of detailed profiles of Tay Sachs disease therapeutic products with key coverage of developmental activities including technology, collaborations, licensing, mergers and acquisition, funding, designations and other product related details

Detailed Tay Sachs disease Research and Development progress and trial details, results wherever available, are also included in the pipeline study

Therapeutic assessment of the active pipeline products by development stage, product type, route of administration, molecule type, and MOA type

Coverage of dormant and discontinued pipeline projects along with the reasons if available across Tay Sachs disease

Reasons to Buy

Establish a comprehensive understanding of the current pipeline scenario across Tay Sachs disease to formulate effective R&D strategies

Assess challenges and opportunities that influence Tay Sachs disease R&D

Develop strategic initiatives by understanding the focus areas of leading companies.

Gather impartial perspective of strategies of the emerging competitors having potentially lucrative portfolio in this space and create effective counter strategies to gain competitive advantage. Get in detail information of each product with updated information on each project along with key milestones. Devise Tay Sachs disease in licensing and out licensing strategies by identifying prospective partners with progressing projects for Tay Sachs disease to enhance and expand business potential and scope. Our extensive domain knowledge on therapy areas support the clients in decision-making process regarding their therapeutic portfolio by identifying the reason behind the inactive or discontinued drugs.

Table of Content for Tay-Sachs Disease Pipeline Insight Market Research Report:Chapter One: Report IntroductionChapter Two: Tay-Sachs Disease (GM2 gangliosidosis, type 1, HexA deficiency, Hexosaminidase A deficiency, Hexosaminidase alpha-subunit deficiency (variant B))Chapter Three: Tay-Sachs Disease Current Treatment PatternsChapter Four: Tay-Sachs Disease Mart Researchs Analytical PerspectiveChapter Five: Tay-Sachs Disease Pipeline TherapeuticsChapter Six: Tay-Sachs Disease -Products AnalysisChapter Seven: Recent TechnologiesChapter Eight: Tay-Sachs Disease Key CompaniesChapter Nine: Tay-Sachs Disease Key ProductsChapter Ten: Dormant and Discontinued ProductsChapter Eleven: Tay-Sachs Disease Unmet NeedsChapter Twelve: Tay-Sachs Disease Future Perspectives

List of Tables for Tay-Sachs Disease Pipeline Insight Market Research Report:Table 1. Diagnostic GuidelinesTable 2. Treatment GuidelinesTable 3. Assessment SummaryTable 4. Company-Company Collaborations (Licensing / Partnering) AnalysisTable 5. Tay-Sachs Disease Acquisition AnalysisTable 6. Assessment by Phase of DevelopmentTable 7. Assessment by Product Type (Mono / Combination)Table 8. Assessment by Stage and Product TypeTable 9. Assessment by Route of AdministrationTable 10. Assessment by Stage and Route of AdministrationTable 11. Assessment by Molecule TypeTable 12. Assessment by Stage and Molecule TypeTable 13. Assessment by MOATable 14. Assessment by Stage and MOATable 15. Late Stage Products (Phase-III)Table 16. Mid Stage Products (Phase-II)Table 17. Early Stage Products (Phase-I)Table 18. Pre-clinical and Discovery Stage ProductsTable 19. Inactive ProductsTable 20. Dormant ProductsTable 21. Discontinued Products

To Check Discount on Tay-Sachs Disease Pipeline Insight Market Research Report @ https://martresearch.com/contact/discount/2/42159

About us: Research is and will always be the key to success and growth for any industry. Most organizations invest a major chunk of their resources viz. time, money and manpower in research to achieve new breakthroughs in their businesses. The outcome might not always be as expected thereby arising the need for precise, factual and high-quality data backing your research. This is where MART RESEARCH steps in and caters its expertise in the domain of market research reports to industries across varied sectors.

Contact Us:

Mart Researchsales@martresearch.com+1-857-300-1122

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Tay-Sachs Disease Pipeline Insight Market Research Report 2019: by Trends, Development, Types, Therapeutics, Drugs, Clinical Trials, Competitive...

CRISPR Therapeutics (CRSP) has been on my watchlist for a couple of years but the stars never aligned for me to pull the trigger on a buy. Due to some recent updates, I am moving CRSP up to the top of my year-end shopping list and will be stalking an entry point in the coming weeks or months.

I intend to discuss the primary reasons why I have waited for an entry, as well as what has tempted me to start a position. In addition, I discuss some of my leading downside risks associated with this ticker and how I plan to manage my potential position over the next year.

(Image Source: CRISPR)

CRISPR Therapeutics is a leader in gene editing, specifically in the advancement of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 "CRISPR-Cas9". CRISPR-Cas9 is a gene therapy, however, it is a revolutionary technology that intends to edit the deleterious gene. This is executed by altering explicit genomic sequences that should correct the bad gene or to alleviate the symptoms of the disease. Essentially, CRISPR is attempting to create curative gene therapies for both rare and common diseases.

CRISPR's programs can be divided up into ex vivo, where the company edits cells outside of the body and in vivo, the CRISPR-Cas9-based therapeutic targeted directly into the cells inside the body. CRISPR's leading pipeline programs take aim at hemoglobin related genetic disorders such as transfusion-dependent beta-thalassemia "TDT" and severe sickle cell disease "SCD". Both conditions desperately need a curative therapy because the current standard-of-care is insufficient. In addition to gene editing, the company has several gene-edited allogeneic cell therapy programs, including a few CAR-T candidates for hematological and solid tumor cancers. Furthermore, the company is taking gene-editing into regenerative medicines to address Type 1 diabetes, as well as taking on DMD and few other indications (Figure 1).

Figure 1: CRISPR Pipeline (Source: CRSP)

CRISPR-Cas9 for gene editing was co-invented by Dr. Emmanuelle Charpentier, who is one of CRISPR's founding members. The company now has the rights to Dr. Charpentier's CRISPR-Cas9 technologies, as well as some supplementary technology from other in-licensing efforts. What is more, CRISPR has a strong list of partnerships that will maximize CRISPR-Cas9's ability both clinically and commercially.

CRISPR has always been on my radar and I have admittedly traded the ticker a few times. However, I have been very cautious about investing in the company for a few reasons. One of which, is the fact that it is named after the technology associated with the gene therapies. Although there are other types of gene therapies, CRISPR appears to be the "brand" or term the market associates with all things gene therapy. Consequently, any bad news, setback, or regulatory failure in gene therapy has had a negative impact on the ticker. Essentially, CRISPR becomes a punching bag for anything that goes wrong in the industry. CRSP experienced strong selling pressure following Sarepta Therapeutics (SRPT) receiving a CRL for their DMD gene therapy. As a result, the stock fell from just under $50 a share to ~$43 per share in a few days. Of course, the rest of the industry experienced some selling pressure, but it appears CRSP gets the worst of it. As a result, I have been reluctant to commit to CRSP knowing that it will always be a target for shorts.

Another reason why I have passed on CRSP was due to its early pipeline. The company's pipeline is still mostly pre-clinical, so I would have been investing in science and not a mature product portfolio. Although I am happy to invest in an early-stage biotech/pharma company, I wanted to see if the FDA was willing to allow gene-editing therapies to be put into humans considering the controversy associated with the technology.

My last reason for holding off an investment was the valuation. The company's market valuation appeared to have a premium price on it. Admittedly, the company's high-priced valuation was due to its name and the hype around the gene therapy and not from a fundamental perspective. Although I am sold on the technology, I wasn't going to commit to a long-term investment to an early-stage company that is years away from a pivotal trial, regardless of the technology was from one of the co-founders of the CRISPR-Cas9.

In general, I knew the company was too early in the regulatory process and I expected the ticker to be toyed around with by traders and analysts. Therefore, I wanted to save myself from an unwanted rollercoaster ride of an investment.

The company is now a clinical-stage gene-editing company, which eliminates one of the reasons why I decided to hold off on starting a long-term investment. CRISPR's lead product candidate, CTX001, is ex-vivo CRISPR therapy that is being developed in collaboration with Vertex Pharmaceuticals (VRTX) for TDT or severe SCD. CTX001 is essentially a process that requires the company to engineer a patient's hematopoietic stem cells to increase the levels of fetal hemoglobin "HbF" in red blood cells.

Figure 2: CTX001 SCD (Source: CRSP)

The increase of HbF has the potential to assuage the need for transfusions for TDT and SCD patients.

Figure 3: CTX001 HbF (Source: CRSP)

CRISPR Therapeutics is enrolling in both Phase I/II studies of CTX001 in TDT and severe SCD. The company expects preliminary safety and efficacy data before the year-end. So far, the first TDT patient treated with CTX001 remains "transfusion independent, greater than four months following engraftment."

Now that CXT001 is in the clinic, we can expect several catalysts to come from these programs. Again, I did believe in the technology but the market needs to see that the pre-clinical data will transfer into humans. If the data is promising, we can expect an increase in attention from the market and from Street analysts. The company is expecting to report preliminary results for CTX001 by year-end, so I wouldn't mind having some skin-in-the-game ahead of that readout.

Another reason for a buy is the expanding use of the company's CRISPR-Cas9 technology. In addition to gene editing, the CRISPR-Cas9 has the potential to generate next-gen CAR-T therapies that may be superior to the contemporary autologous CAR-T (Figure 4).

Figure 4: CAR-T Highlights (Source: CRSP)

The company has programs including CTX110, a healthy donor-derived gene-edited allogeneic CAR-T therapy targeting CD19. In pre-clinical mouse studies, the company detected that CTX110 extended the survival in CD19-positive xenograft tumors. In addition to CTX110, the company has CTX120 that is targeting BCMA in multiple myeloma and CTX130 that could target both solid tumors and hematologic malignancies.

Figure 3: CTX110 & CTX120 (Source: CRSP)

In preclinical studies both CTX120 and CTX130 were able to record "complete tumor elimination" in their respective targets.

Figure 4: CTX130 (Source: CRSP)

In addition to cell-therapies, CRISPR is using their ex vivo gene-editing in regenerative medicine by using stem cells to restore or exchange damaged or malfunctioning tissue. Their leading regenerative program is diabetes with their partner, ViaCyte Inc (Figure 5).

Figure 5: In Diabetes (Source: CRSP)

CRISPR has other in vivo disease targets that impact the liver, lung and muscle. These will use the company's lipid nanoparticle-based delivery vehicles "LNPs" and AAV vectors to help deliver the genetic material.

Figure 6: Neuro & Liver (Source: CRSP)

Other notable programs include Glycogen Storage Disease Type Ia "GSDIa", DMD and cystic fibrosis.

Admittedly, I have always seen CRISPR as a pure gene-editing company, however, they have a diverse pipeline and the technology to expand it into numerous other indications and areas of therapy. I expect the company will expand on their research efforts, which should increase the pending value of the company and add some catalysts to the calendar.

The company intends to advance their CRISPR-Cas9 therapeutics both autonomously and in strategic partnerships (Figure 7). The company has closed three major partnerships with Vertex, Casebia/Bayer (OTCPK:BAYRY) and ViaCyte. These partnerships not only provide CRISPR with some support, but they confirm that other reputable companies see CRISPR as a leader in this field.

Figure 7: CRSP Partnerships (Source: CRSP)

As the company expands its pipeline, I anticipate an increase in the number of strategic partnerships and deals. In fact, the company recently announced a partnership with KSQ Therapeutics to in-license IP to advance their cell therapy programs.

My final reason for stalking an entry is the improved risk/reward scenario. The stock appears to have lost some momentum and has had a relatively flat 2019. The stock has recently experienced a strong pull-back, yet, the company has made substantial progress in both the pipeline and strategic collaborations.

Figure 8: CRSP Daily (Source: Trendspider)

This recent pull-back has cut the market cap down to ~$2B which I believe is fair considering the long-term outlook for the company.

Figure 9: CRSP Valuation (Source: Seeking Alpha)

Looking at the CRSP's annual revenue estimates (Figure 10), we can see the Street expects the company to have relatively flat revenues for the next couple of years and will start to experience strong revenue growth in the second half of the next decade. This rapid growth is expected to drop the forward price-to-sales ratio below 1x at some point in 2027. The sector's average price-to-sales is about 5x, so that would equal ~$13B market cap in 2027.

Figure 10: CRSP Annual Revenue Estimates (Source: Seeking Alpha)

I understand this is years away, but I expect these estimates to only improve as the company continues to add pipeline programs and other strategic partnerships. Indeed, I could wait another year or two to further reduce my risk and cost for time. However, I don't want to be left out of this ticker if the company starts reporting curative results in multiple programs. What would happen if the company demonstrates the potential to cure Type 1 diabetes? Do you think it will be trading at a $2B market cap? What about if they cure cystic fibrosis? Sickle Cell? Eliminate renal cancer with an autologous CAR-T therapy? I believe the company would be undervalued at $2B even if they only cured one of these indications. Assuming the company has at least one winner in their current pipeline, I have to say the current risk/reward is enticing enough for me to start a speculative position.

I believe the biggest threat to CRISPR comes from the impressive competition from other gene therapy companies and institutions. These include companies that are working on CRISPR-Cas9 technology such as Intellia Therapeutics (NTLA) and most notably Editas Medicine (EDIT). Other gene-editing companies such as bluebird bio (BLUE), Sangamo Therapeutics (SGMO), Cellectis (CLLS), Precision BioSciences (DTIL), and Allogene Therapeutics (ALLO) use other gene-editing platforms. There is a multitude of gene therapy companies that I didn't mention, but I think you get my point. Some of these companies are not in the same league as CRISPR, however, I believe CRISPR's biggest threat is something that is currently in a theoretical stage or perhaps hasn't been thought of yet. As gene therapy products begin to hit the market and start dethroning current standard-of-care therapies, I expect big pharma to start devoting a larger percentage of their R&D to gene therapies. As a result, more universities and institutions will start pioneering new CRISPR tech and perhaps another level of gene editing. If they are successful, they will most likely dethrone CRISPR-Cas9 as cutting-edge technology.

CRISPR is a developmental biotech company, so of course, the financials will be an issue until the company has a product on the market. At the end of Q2, the company had $427.9M in the bank. The company's R&D expenses were $39.5M for Q2, which led to a net loss of $53.7M. Usually, I would consider $428M to be a strong cash position for pre-revenue biotech, but I don't think we are seeing peak cash-burn. The company has several programs that haven't even hit the clinic yet, so we can expect that cash position to melt rapidly in the coming years. In fact, the company recently secured a $200M at-the-market sale of common stock, so we should expect the company to tap the market when they need to. Even then, investors need to accept the strong possibility the company will execute secondary offerings in the future.

CRISPR Therapeutics has evolved over the past couple of years and so has my view of a potential investment. The company's premium name brought a premium price, which generated a substantial amount of attention from traders who have created detached or arbitrary valuations for the ticker. Now, the company has moved into the clinic and will be generating data that could reveal curative level results for dreadful diseases and conditions. If CRISPR is able to gain regulatory approval, the product could replace the current standard-of-care for the indication and eventually dominate as patients demand a cure, rather than dealing with a lifetime of medications or procedures.

Due to this potential, I am moving CRSP up to the top of my shopping list as we close out 2019. I expect many of the speculative biotech names to experience end-of-the-year tax selling, so I am going to keep a close eye on the charts to see if I can get a nice discount to establish a large position. In the meantime, I rely on the chart's technicals to find an entry. Returning to figure 8, we can see the stock has returned to its previous trading range after a month of selling pressure. If the share price is able to hold this area over the next couple of weeks, I will look to click the buy button on a low volume day. If the stock breaks below $35, I will most likely hold off on a buy until the end of the year. Once I have established a position, I will look to add to my position following data readouts with a goal to have a full-sized position by the end of 2021.

Disclosure: I am/we are long SRPT. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: I am also long BLUE.

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CRISPR Therapeutics: At The Top Of My Shopping List - Seeking Alpha

SAN DIEGO, Oct. 22, 2019 (GLOBE NEWSWIRE) -- CV Sciences, Inc. (OTCQB:CVSI) (the Company, CV Sciences, our, us or we), a preeminent supplier and manufacturer of hemp cannabidiol (CBD) products, today announced the appointment of Dr. Paul Blake to its Board of Directors effective October 21, 2019.

We are very pleased to have Dr. Blake join our Board of Directors, said Joseph Dowling, Chief Executive Officer of CV Sciences. His decades of experience leading pharmaceutical companies will be invaluable to us as we continue to strengthen our industry leadership position in CBD consumer products and drug development.

Dr. Blake brings with him deep expertise in clinical research, development, and medical affairs within the pharmaceutical industry. He currently serves as Chief Medical Officer at Heron Therapeutics Inc., a commercial-stage biotechnology company focused on improving the lives of patients suffering from pain or cancer by developing best-in-class treatments. At Heron, Dr. Blake is responsible for clinical research, medical affairs and drug safety.

Prior to joining Heron, he served as Chief Medical Officer of BioDelivery Sciences International, and before that he was the Chief Development Officer at Oxford BioMedica, a gene therapy company. His prior positions include Chief Medical Officer and Senior Vice President of Clinical Research and Development of Aeterna Zentaris, Inc., and Senior Vice President and then Executive Vice President of Worldwide Medical and Regulatory Operations at Cephalon, Inc. From 1992 to 1998, he held the position of Senior Vice President and Medical Director, Clinical Research and Development at SmithKline Beecham Pharmaceuticals (now GSK). Prior to that, he worked for ICI Pharmaceuticals (now Astra Zeneca) and G.D. Searle.

Dr. Blake is qualified in medicine from the Royal Free Hospital School of Medicine, London University. He is a Fellow of the Royal College of Physicians and a Fellow of the Faculty of Pharmaceutical Medicine of the Royal College of Physicians. He is also a Fellow of the American College of Clinical Pharmacology.

Dr. Blake has been involved in the development of several pharmaceutical drugs including: Tenormin, Zestril, Kytril, Relafen, Paxil, Coreg, Havrix, Hycamtin, Famvir, Requip, Avandia, Provigil and Fentora.

Dr. Blake served on the board of Memory Pharmaceutical, Inc., until it was purchased by Roche in 2009 and was a founding board member of Protez Pharmaceuticals, Inc., until it was purchased by Novartis in 2008. He was also a Director of ViaCell, Inc., until its purchase by Perkin Elmer in 2007 and of Oxford BioMedica from 2008 until 2016.

He has also served as a member of the Inter-Company Collaboration for AIDS Drug Development and as a trustee of the Childrens Health Fund.

I am excited to join CV Sciences Board of Directors and to contribute to the Companys mission of providing the highest-quality CBD products to consumers and patients, said Dr. Blake. CV Sciences is a leading pioneer in the CBD space and is uniquely positioned to continue to bring innovative products and novel therapeutics utilizing CBD to market.

About CV Sciences, Inc.

CV Sciences, Inc. (OTCQB:CVSI) operates two distinct business segments: a consumer product division focused on manufacturing, marketing and selling plant-based CBD products to a range of market sectors; and a drug development division focused on developing and commercializing CBD-based novel therapeutics utilizing CBD. The Companys PlusCBD Oil products are sold at more than 5,500 retail locations through the U.S. and it is the top-selling brand of hemp-derived CBD on the market, according to SPINS, the leading provider of syndicated data and insights for the natural, organic and specialty products industry. CV Sciences state-of-the-art facility follows all guidelines for Good Manufacturing Practices (GMP) and the Companys full spectrum hemp extracts are processed, produced, and tested throughout the manufacturing process to confirm the cannabinoid content meets strict company standards. With a commitment to science, PlusCBD Oils benefits in healthy people are supported by human clinical research data, in addition to three published clinical case studies available on PubMed.gov. PlusCBD Oil was the first hemp CBD supplement brand to invest in the scientific evidence necessary to receive self-affirmed Generally Recognized as Safe (GRAS) status. CV Sciences, Inc. has primary offices and facilities in San Diego, California. Additional information is available from OTCMarkets.com or by visiting http://www.cvsciences.com.

FORWARD-LOOKING DISCLAIMER

This press release may contain certain forward-looking statements and information, as defined within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, and is subject to the Safe Harbor created by those sections. This material contains statements about expected future events and/or financial results that are forward-looking in nature and subject to risks and uncertainties. Such forward-looking statements by definition involve risks, uncertainties.

CONTACT INFORMATION:Investor Contact:ICRScott Van Winkle617-956-6736scott.vanwinkle@icrinc.com

Media Contact:ICRCory Ziskind646-277-1232cory.ziskind@icrinc.com

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CV Sciences, Inc. Appoints Dr. Paul Blake to its Board of Directors - GlobeNewswire

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Gene Therapy Market 2019 Global Opportunity Analysis and Industry Forecast to 2025 - Honest Newsly

Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline Insight Market Research 2019 report by Mart Research outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Fanconi Anemia (FA) Fanconi Hypoplastic Anemia pipeline landscape is provided which includes the disease overview and Fanconi Anemia (FA) Fanconi Hypoplastic Anemia treatment guidelines. The assessment part of the report embraces, in depth Fanconi Anemia (FA) Fanconi Hypoplastic Anemia commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Fanconi Anemia (FA) Fanconi Hypoplastic Anemia collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

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According to the Cancer and Blood Disorders Center, Fanconi Anemia (Fanconi hypoplastic anemia, Fanconi pancytopenia, Fanconi panmyelopathy) is a rare inherited disease characterized by multiple physical abnormalities, bone marrow failure, and a higher than normal risk of cancer. Researchers have shown that mutations in one of at least 15 different genes can cause FA. The proteins normally produced by these genes form a kind of cellular machine that helps detect and repair damaged DNA in blood stem cells and other cells in the body, in FA this damaged DNA repair is slowed. Therefore, blood stem cells (in the bone marrow) accumulate damaged DNA and do not survive. FA is usually discovered between birth and age 10-15 years; however, there also have been cases identified in adulthood. FA occurs equally in males and females. It has been identified in all ethnic groups. Researchers continue to clone and characterize the genes responsible for FA, which is bringing considerable progress in the diagnosis and understanding of this disease. It is more common in male as compared to female.

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This report provides an in-depth Commercial Assessment of therapeutic drugs have been included which comprises of collaborations, Licensing, Acquisition Deal Value Trends. The sub-segmentation is described in the report which includes Company-Company Collaborations (Licensing / Partnering), Company-Academia Collaborations, and Acquisition analysis in both Graphical and tabulated form.

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Table of Content for Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline Insight Market Research Report:Chapter One: Report IntroductionChapter Two: Fanconi Anemia (Fanconi hypoplastic anemia, Fanconi pancytopenia, Fanconi panmyelopathy)Chapter Three: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Current Treatment PatternsChapter Four: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Mart Researchs Analytical PerspectiveChapter Five: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline TherapeuticsChapter Six: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia -Products AnalysisChapter Seven: Recent TechnologiesChapter Eight: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Key CompaniesChapter Nine: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Key ProductsChapter Ten: Dormant and Discontinued ProductsChapter Eleven: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Unmet NeedsChapter Twelve: Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Future Perspectives

List of Tables for Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Pipeline Insight Market Research Report:Table 1. Diagnostic GuidelinesTable 2. Treatment GuidelinesTable 3. Assessment SummaryTable 4. Company-Company Collaborations (Licensing / Partnering) AnalysisTable 5. Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Acquisition AnalysisTable 6. Assessment by Phase of DevelopmentTable 7. Assessment by Product Type (Mono / Combination)Table 8. Assessment by Stage and Product TypeTable 9. Assessment by Route of AdministrationTable 10. Assessment by Stage and Route of AdministrationTable 11. Assessment by Molecule TypeTable 12. Assessment by Stage and Molecule TypeTable 13. Assessment by MOATable 14. Assessment by Stage and MOATable 15. Late Stage Products (Phase-III)Table 16. Mid Stage Products (Phase-II)Table 17. Early Stage Products (Phase-I)Table 18. Pre-clinical and Discovery Stage ProductsTable 19. Inactive ProductsTable 20. Dormant ProductsTable 21. Discontinued Products

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Fanconi Anemia (FA) Fanconi Hypoplastic Anemia Fanconi Hypoplastic Anemia Pipeline Insight Market Research Report 2019: by Trends, Development, Types,...