Monthly Archives: December 2020

Israeli biotech Pluristem is canning its experimental phase 3 critical limb ischemia therapy after an outside review said it was no good.

Haifa, Israel-based Pluristems R&D operation is built upon placenta-derived adherent stromal cells, which the biotech has designed for use in patients of all human leukocyte antigen types. This approach is made possible by the low immunogenicity of the cells. Once inside the body, Pluristem hopes the cells will drive the healing of injured tissue.

But one of its leading contenders using this approach has been judged a failure in phase 3: An independent data monitoring committee (DMC) took a look at the ongoing data for its pivotal phase 3 in patients with critical limb ischemia (CLI), a severe obstruction of the arteries which markedly reduces blood flow to the extremities and can lead to amputation.

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The DMC said the test was unlikely to meet the primary endpoint, and that the CLI study population has experienced a substantial low number of events (major amputation of the index leg or death), different from what is known in clinical medicine for the rate of these events in this patient population. The lower than anticipated event rate in the placebo group reduced the statistical power of the study to meet its primary endpoint.

The biotech is now tossing out the therapy and will instead focus on other pipeline areas, including a long-shot stem cell attempt at treating COVID-19. The biotechs shares fell nearly 40% on the news.

We are deeply disappointed by the outcome of the CLI interim analysis. In light of the DMCs recommendation, we decided that it would be in the best interests of the company and its shareholders to terminate the CLI study and focus our resources and efforts on our other lead indications, said Pluristem CEO and President Yaky Yanay.

We expect to present topline clinical results during calendar year 2021, including our phase 3 study in muscle regeneration following hip fracture, phase 2 studies in Acute Respiratory Distress Syndrome associated with COVID-19 and our phase 1 study in incomplete hematopoietic recovery following hematopoietic cell transplantation. Pluristem is well positioned to advance and support future development of these indications.

Last year, Pluristem penned a deal with NASA to assess its cell therapies against the health problems caused by spending time in space, teaming up with NASAs Ames Research Center for the project, which focuses on using its PLX placenta-derived cell therapies to try to prevent or treat medical conditions that can occur during and after space missions, including conditions that affect the blood, bone, muscle, brain and heart.

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NASA-partnered Pluristem crashes to Earth as it axes leading therapy - FierceBiotech

It takes a lot of poppies to make serious painkillers. Morphine is classed as an essential medicine by the World Health Organization, but it wouldnt exist withoutPapaver somniferum(better known as the opium poppy).Around 100,000 hectares of the flowers are cultivated every year primarily in Australia, Spain, France, India, Turkey and Hungary to meet demand for opioid medication worldwide. Approximately 800 tons of the natural opiates morphine and thebaine are extracted from the harvested straw, some of which are then chemically converted into higher value drugs, such as codeine, oxycodone and hydrocodone.

Although fields of beautiful blooms sound idyllic, industrial poppy farming isnt easy.

Pests, disease and poor weather conditions can dramatically impact the yield. Plus, growing drugs from plants takes a long time and the poppies themselves contain very low levels of the active ingredient. If there is a spike in demand for opioid medicines, the supply chain can struggle to respond fast enough. These issues mean problems for the pharmaceutical industry, which in-turn means drug shortages for doctors and patients.

Medicines derived from nature (as around 40% of our drugs are) are particularly vulnerable in times of uncertainty. During the Covid-19 crisis, weve seen that supply chain problems can have a human cost. In the spring, the US Food and Drug Administration reported a shortage of the opioids needed to safely keep patients on ventilators.

There could be a better way of making the rare compounds found in nature and avoiding similar supply chain issues, says Stanford University adjunct professor Christina Smolke. In 2015, she and a small team of researchers proved that opioids could be produced using genetically-modified yeast.

Smolkes breakthrough involved a process weve known about for centuries: fermentation. Give brewers yeast a little sugar and under the right conditions itll reward you with alcohol and carbon dioxide.

Smolke figured fermentation had the power to speed up drug manufacturing with yields seen in day or weeks, rather than months or years as with crop farming. It would mean supply could be easily increased if there was an unexpected event.

But plant-derived medicines are made from more complex stuff than ethanol or carbon dioxide. If you look at the types of molecules plants make, theyre incredibly complicated from a structural perspective, says Smolke. The way they are able to survive and interact with their environment is through chemistry.

These molecules are almost impossible to replicate in the laboratory using synthetic chemistryso Smolke, who has a chemical engineering background, instead turned to synthetic biology. First, she identifiedwhich plant enzymes are responsible for the chemical reactions that lead to the useful compounds.

Then its a case of making the genetic recipe for these chemicals and translating it into a language the yeast can understand. Synthetic DNA is then inserted into the yeast, which tells it to make the desired compounds out of the sugar and amino acids the scientists feed to it.

To coax the yeast to make the opioid hydrocodone, the team translated 23 proteins from the poppy into the microbe. After her initial breakthrough, Smolke formed start-up synthetic biology company Antheia to focus on creasing ever-more complex medicines using yeast.

Its not the first time a microbe has been used to make medicine. In 1982, Eli Lily introduced synthetic insulin Humulin to the market, a breakthrough drug for people with diabetes. Before, insulin had to be extracted from the pancreases of cows or pigs. This caused allergic reactions in some patients as animal insulin isnt an exact match for the hormone produced in healthy human pancreases.

Humulin is made by introducing human DNA into a bacterial host cell. As the bacteria multiply, the medicine is produced. Human insulin can now also be made using yeast cells and fermentation. And since 2014, Sanofi has also used yeast to produce artemisinic acid to make the anti-malarial artemisinin, which is usually sourced from the sweet wormwood plant.

In August 2020, Smolke and colleagues announced inNaturethat they had successfully produced neuromuscular blockers used in Parkinsons disease and intestinal disorders. These chemicals were the tropane alkaloids hyoscyamine and scopolamine, which are naturally found in the nightshade family of plants.

As with the poppy, cultivating nightshades is subject to global supply risks, such as environmental disasters and the ongoing pandemic. Shortages of alkaloid-based medicines are unfortunately common.

To achieve tropane alkaloid synthesis in yeast, Smolke and her team had to overcome several challenges. As before, they first needed to work out which enzymes the nightshade plant uses to make the compounds and how to get those to work in a yeast host.

But the biggest hurdle was realising the critical chemical reactions required to make tropane alkaloids are segregated across different subcellular compartments, cells or tissues in the plant. It would be tough to recapitulate this in single-cell yeast.

In many cases, its not enough just to get the protein made because it wont have the correct kind of biochemical environment for it to actually perform its reaction, says Smolke. A lot of times where these types of projects fail you can identify the enzyme, but you cant get the yeast to make it in a way that the reaction actually happens.

After a gruelling coding process involving 26 genes from ten different organisms, they were able to create six different subcellular compartments within the yeast cell to make sure the right chemical reaction would occur at the right time.

What we also did beyond distributing the enzymes was incorporating other proteins like transporters that could be localised to the membranes of these compartments, Smolke explains.

This allowed for more efficient routing of the metabolites from one set of chemistries to the next. In doing so, the team transformed the yeast into a chemical factory, in which different synthesis steps are conducted in separate reactors to ensure each reaction has the optimum conditions.

TheNaturepaper is further proof that brewers yeast can be a platform for making some of natures most valuable and complex molecules. The next step for Smolke will be convincing the pharmaceutical industry that this could be the future of drug manufacturing. She and her team will need to prove the technology can mass-produce molecules faster, cheaper and more reliably than the original farming methods.

In the latest work, only a few milligrams of tropane alkaloids per litre of yeast culture were produced not yet a competitive alternative to production through plant extraction. However, Smolke says Antheia is constantly tinkering with the yeast to improve its efficiency so a larger amount of compound over a given period time is produced.

As these examples scale, well see there are new ways of structuring supply chains that will bring more resiliency and control, Smolke says. This is going to open up the pharmaceutical industry.

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Brewprint: using yeast to make plant-based drugs - pharmaceutical-technology.com

Event will review the companys novel approach to inducing fetal hemoglobin

Live webcast on December 15, 2020 at 8:30am ET

CAMBRIDGE, Mass., Dec. 09, 2020 (GLOBE NEWSWIRE) -- Fulcrum Therapeutics, Inc.(Nasdaq: FULC), a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases, today announced that it will host a Key Opinion Leader (KOL) meeting on Tuesday, December 15, 2020 from 8:30am 10:00am ET to discuss the companys program with FTX-6058 for select hemoglobinopathies, including sickle cell disease and beta-thalassemia.

Dr. Maureen Achebe and Dr. Gerd Blobel will join senior executives from Fulcrum in presenting and discussing sickle cell disease, the treatment landscape and the FTX-6058 program followed by a Question and Answer session. Maureen Achebe, MD is currently Clinical Director, Non-Malignant Hematology Clinic, Assistant Director, Brigham and Womens Hospital Outpatient Infusion Center, Director, Brigham and Womens Hospital Sickle Cell Program and Assistant Professor of Medicine, Harvard Medical School. Gerd Blobel, MD, PhD is currently Frank E. Weise III professor of pediatrics, University of Pennsylvania and Co-director Epigenetics Institute. He also holds the Frank E. Weise III Endowed Chair of Pediatrics at The Childrens Hospital of Philadelphia and the Perelman School of Medicine.

The live webcast will be accessible through the Investor Relations section of the companys website https://ir.fulcrumtx.com/events-and-presentations. Following the live webcast, an archived replay will also be available on the website for up to 90 days.

About FTX-6058FTX-6058 is a highly potent small molecule inhibitor of EED capable of inducing robust HbF protein expression in cell and murine models. Fulcrum believes the pharmacokinetics and human dose simulations support that FTX-6058 may be given as a once daily oral compound. The validation of EED as a target for sickle cell disease and the discovery of FTX-6058 as a novel HbF-inducing small molecule were conducted using Fulcrums proprietary Product Engine. The companys composition of matter patent covering FTX-6058 and related structures has been granted. Preclinical data with FTX-6058 showed an increase in HbF levels up to approximately 30% of total hemoglobin. Fulcrum has initiated a Phase 1 trial with FTX-6058 in healthy volunteers.

About Fulcrum TherapeuticsFulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrums proprietary product engine identifies drug targets which can modulate gene expression to treat the known root cause of gene mis-expression. The company has advanced losmapimod to Phase 2 clinical development for the treatment of facioscapulohumeral muscular dystrophy (FSHD) and Phase 3 for the treatment of COVID-19. Fulcrum has also advanced FTX-6058, a small molecule designed to increase expression of fetal hemoglobin for the treatment of sickle cell disease and beta thalassemia, into Phase 1 clinical development.

Please visit http://www.fulcrumtx.com.

Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the development status of the Companys product candidates and the potential advantages and therapeutic potential of the Companys product candidates. All statements, other than statements of historical facts, contained in this press release, including statements regarding the Companys strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, will, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with Fulcrums ability to obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in clinical trials; initiate and enroll clinical trials on the timeline expected or at all; correctly estimate the potential patient population and/or market for the Companys product candidates; replicate in later clinical trials positive results found in preclinical studies and/or earlier-stage clinical trials of losmapimod and its other product candidates; advance the development of its product candidates under the timelines it anticipates in current and future clinical trials; obtain, maintain or protect intellectual property rights related to its product candidates; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the Risk Factors section, as well as discussions of potential risks, uncertainties and other important factors, in the Companys most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Companys views as of the date hereof and should not be relied upon as representing the Companys views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Companys views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so.

Contact:

Investors:Christi WaarichDirector, Investor Relations andCorporate Communications 617-651-8664cwaarich@fulcrumtx.com

Stephanie Ascher Stern Investor Relations, Inc.stephanie.ascher@sternir.com212-362-1200

Media: Kaitlin GallagherBerry & Company Public Relationskgallagher@berrypr.com212-253-8881

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Fulcrum Therapeutics to Host Virtual Key Opinion Leader Event Featuring FTX-6058 for Sickle Cell Disease - GlobeNewswire

JERUSALEM, Dec. 8, 2020 /PRNewswire/ --NeuroGenesis, a clinical-stage biopharmaceutical company advancing innovative cell therapies to combat myelin-related neurodegenerative diseases, and Hadassah Medical Center announced today highly positive results from a placebo-controlled Phase 2 clinical trial, headed by Prof. Dimitrios Karussis, together with Dr. Petrou Panayiota and Dr. Ibrahim Kassis from Hadassah Medical Center in Jerusalem, assessing the impact of NG-01 autologous proprietary subpopulation of mesenchymal stem cells (MSCs) on patients with progressive multiple sclerosis (MS).

The results, recently published in Brain, a prestigious peer-reviewed journal published by Oxford University, and highlighted in the "Editor's Choice", show that:

"The treatment was well tolerated and the trial met all of its primary endpoints," said Professor Dimitrios Karussis, lead principle investigator and Director of MS Center at Hadassah Medical Center, Jerusalem. "The patients' improvement was in many cases quite remarkable and included regain of motor function and noticeable effects on their cognitive abilities."

Prof Karussis added, "Although we currently have several good treatment options for relapsing remitting MS, we fall short in providing effective treatment for progressive MS that could substantially suppress the progression of disability. This trial provides encouraging results and suggests a potential for a new approach that may not only slow down the progression of the disease but even induce improvement and promote repair mechanisms in progressive MS."

The technology is now further developed by NeuroGenesis, following a license from Hadasit, Hadassah Medical Center Technology Transfer Company.

Neurogenesis' technology entails collecting bone marrow from the patient. Then by utilizing a proprietary process, a unique subpopulation of bone marrow cells is identified, cultured and enhanced towards remyelinating biofactory cells (NG-01) that also possess neurotrophic immunolatory and neuroprotective properties. The NG-01 cell population is injected directly into the central nervoussystem (through the cerebrospinal fluid), where the cells home-in on the damaged area, take up residence and produce significant amounts of neurotrophic factors.

"Progressive MS is a chronic, debilitating disease with no satisfactory treatment to improve or reverse established disability," said Tal Gilat, CEO of NeuroGenesis. "We are therefore extremely pleased to witness the significant positive effect of our NG-01 cells. Following recent interactions with the FDA, we look forward to confirming and expanding these findings in a large multi-center MS trial, and continuing advanced studies in additional indications such as ALS."

About the Phase 2 trial of NG-01

The Phase 2, randomized, double-blind, placebo-controlled, clinical trial assessed the safety, tolerability and efficacy of transplantation of NG-01 in people with progressive MS. The study enrolled 48 participants with progressive MS which were randomized into 3 groups, receiving either an intrathecal or intravenous NG-01 injection, or a placebo injection.

The two predetermined primary endpoints of the trial were: (i) the safety of the intrathecal and intravenous NG-01 treatments assessed by incidence of adverse events versus those in the placebo-treated group; and (ii) the differences among the three groups in the Expanded Disability StatusScale(EDSS) score changes and the proportion of patients with treatment failure, as evidenced by an increase in EDSS (disease progression) score, at 6 and 12 months. Overall, the study duration was 14 months.

About Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease that causes damage in the myelin and the nerve cells of the central nervous system (demyelinating plaques in brain and spinal cord), resulting in cumulating neurological disability. The destruction of the myelin (the covering that protects nerves and promotes the efficient transmission of nerve impulses) causes secondary damage to the nerve cells and progressive atrophy. MS often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Motor problems are common in people with MS. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or paralysis of the muscles of the limbs, difficulty in walking, and poor sphincter control. The condition is also associated with visual problems, such as blurred or double vision or partial or complete vision loss. There is no known cure for multiple sclerosis.The existing treatments are mostly aimed to reduce the incidence of relapses of the disease and slow down the rate of neurological deterioration.

About NeuroGenesis

Neurogenesis is developing cell therapy for neurodegenerative diseases based on a unique approach for sustained delivery of high levels of remyelinating growth factors using the patient's own stem cells. The technology for this unique approach was licensed from Hadasit, theTechnology TransferCompany of Hadassah Medical Organization in Jerusalem, Israel. The Company's lead product is NG-01 for the treatment of progressive Multiple Sclerosis, (in which a placebo-controlled Phase 2 study has been completed and recently published). NG-01 were also tested in two successful Phase 2a trials in ALS patients. Up to today, more than 150 progressive MS and ALS patients from around the world have been treated with Neurogenesis'products via clinical trials (Phase 1 and Phase 2) and compassionate use treatments.

About Hadassah and Hadasit

For more than a century, Hadassah has set the standard of excellence for medical care and research in Israel. Our doctors and scientists are on the frontlines, uniquely positioned to pinpoint ever-evolving medical needs. Their experience and ingenuity have yielded new ideas with huge potential in all areas of medicine, including therapeutics, diagnostic medical devices, and digital health. Hadasit is the technology transfer company of Hadassah Medical Center in Jerusalem. We transform the cutting-edge research coming out of Hadassah into marketable medical technologies. We turn ground-breaking ideas into viable products and services that can change the world and better humanity.

NeuroGenesiscontact:Tsipi HaitovskyGlobal Media LiaisonNeuroGenesis+972-52-5989-892[emailprotected]

Hadassah contact:Hadar ElboimspokeswomanHadassah Medical Organization+ 972- 2-6776079[emailprotected]

SOURCE NeuroGenesis

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Hadassah Medical Center and Neurogenesis Announce Groundbreaking Results from a Phase 2 Study in Progressive Multiple Sclerosis treated with NG-01...

Further understanding is needed of the redox change called reductive stress and its impact on the onset and progression of neurodegeneration.

Further understanding is needed of the redox change called reductive stress and its impact on the onset and progression of neurodegeneration.Cells require a balance among oxidation-reduction reactions, or redox homeostasis. Loss of that balance to create oxidative stress is often associated with neurodegeneration. Less is known about how loss of that balance at the other end of the spectrum reductive stress, or RS may affect neurons.

Now Rajasekaran Namakkal-Soorappan, Ph.D., associate professor in the University of Alabama at Birmingham Department of Pathology, Division of Molecular and Cellular Pathology, and colleagues in the United States and India have shown for the first time that reductive stress promotes protein aggregation in neuroblastoma cells and impairs neurogenesis.

Our data suggest that, despite the association of oxidative stress and neuronal damage, RS can play a crucial role in promoting proteotoxicity, and thereby lead to neurodegeneration, Namakkal-Soorappan said. Moreover, this study adds to the emerging view that the regulation of redox homeostasis, and its impact on diverse diseases, is part of a complex process in which appropriate doses of antioxidants are required only in response to an oxidative or toxic challenge in cells or organisms.

Namakkal-Soorappan and colleagues have previously found that RS is pathogenic in a mouse-model of heart disease, and that RS impairs the regeneration of skeletal muscle in cultured mouse myoblast cells.

In the current study, the researchers used sulforaphane to establish RS in proliferating and differentiating Neuro 2a neuroblastoma cells grown in culture. Sulforaphane activates Nrf2/ARE signaling, leading to antioxidant augmentation. Specifically, they found that sulforaphane-mediated Nrf2 activation diminished reactive oxygen species in a dose-dependent manner leading to RS. The resulting RS abrogated oxidant signaling and impaired endoplasmic reticulum function, which promoted protein aggregation and proteotoxicity, and impaired neurogenesis. This included elevated Tau and -synuclein and their co-localization with other protein aggregates in the cells.

Namakkal-Soorappan says they were also surprised to see that acute RS impaired neurogenesis, as measured by reduced neurite outgrowth and length, and that maintaining the cells in sustained RS conditions for five consecutive generations dramatically reduced differentiation and prevented the formation of axons.

This impairment of neurogenesis occurs through activation of the pathogenic GSK3/Tau cascade to promote phosphorylation of Tau and create proteotoxicity.

Intriguingly, there have been reports of increased levels of enzymes that can promote RS, both in the brains of Alzheimers patients and in the post-mortem brains of Alzheimers and Parkinsons patients. Also, attempts to promote neurogenesis in neurodegenerative diseases using small molecule antioxidants have had poor outcomes.

Rajasekaran Namakkal-Soorappan, Ph.D.Therefore, clinical evidence warrants a closer investigation and further understanding of redox changes and their impact at the onset and progression of neurodegeneration, Namakkal-Soorappan said.

Neurodegenerative diseases, including Alzheimers, Parkinsons and Huntingtons, are a major health problem in aging populations throughout the world.

Co-authors with Namakkal-Soorappan in the study, Reductive stress promotes protein aggregation and impairs neurogenesis, published in the journal Redox Biology, are Kishore Kumar S. Narasimhan, UAB Department of Pathology; Asokan Devarajan, David Geffen School of Medicine, University of California, Los Angeles; Goutam Karan, University of Utah; Sandhya Sundaram, Sri Ramachandra Medical University & Research Institute, Chennai, India; Qin Wang and Thomas van Groen, UAB Department of Cell, Developmental and Integrative Biology; and Federica del Monte, Medical University of South Carolina, Charleston.

Support came from National Institutes of Health grants 2HL118067, HL118067, 2HL118067-7S and AG042860; American Heart Association grant BGIA 0865015F; and grants from the University of Utah and UAB.

In the three studies on RS published in 2020, Namakkal-Soorappans name is listed as Namakkal S. Rajasekaran.

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Reductive stress in neuroblastoma cells aggregates protein and impairs neurogenesis - The Mix

As the precision medicine field evolves and the science behind personalized therapies for complex conditions surges ahead, reimbursement models are racing to catch up. Precision medicine treatments, like cell and gene therapies, tend to have high price tags and novel delivery mechanisms. This makes creating effective payment models for these therapies a challenge, but drug developers and payers are working together to create out-of-the-box solutions.

Determining prices for breakthrough cell and gene therapies is a complicated process, said Laura Okpala, director of reimbursement policy at Gilead Sciences, at the MedCity INVEST Precision Medicine conference. Though there is a strong belief that the pricing process needs to be driven by value value means different things to different people. Biopharmaceutical companies, like Gilead Sciences, must consult with various stakeholders, including patients, caregivers and payers, who all have different perspectives on value.

Part of why the pricing is so difficult is because of the inherent complexities in the healthcare system, Okpala said. When we think of traditionally how drugs are paid for, were thinking about chronic treatment, were thinking about treatment over a long, extended period, treatment over and over again, reimbursement every single time, and that adds up.

But when you think about cell and gene therapies, all those costs and all of that treatment happens upfront, she added. And then you get that durable response, up to four years at this point. And that is really a paradigm shift when you think about [a] healthcare system that really isnt set up to deal with that upfront cost and that value delivered over time.

But the upfront payment is just one of many challenges. Mark Trusheim, strategic director of the NEWDIGS initiative at the MIT Center for Biomedical Innovation, said at the virtual conference that there are two more key challenges that arise: the performance uncertainty regarding these therapies, particularly around their durability, and the actuarial uncertainty it causes for payers. Most of these therapies are for rare conditions, so a single high-cost therapy in any given month can have a negative impact on payers income statements.

To combat these challenges, several innovative reimbursement models have been developed.

One is a model based on treatment milestones. Per this model, a certain amount of money is paid upfront, and if the therapy doesnt show the intended effects in certain predetermined timeframes, the drug developer pays back a portion of the initial payment.

[The model allows] some risk sharing between the developer and the payer, so they dont have to argue quite so much up front, Trusheim said. And the actual product performance [resolves] how much [is] finally the net reimbursement or the net price for that therapy.

This model helps manage the different expectations and fears of both parties, he added.

Another is a subscription-based model, which includes a fixed fee for unlimited access to certain therapies, Trusheim explained. Cigna has an insurance product that offers this reimbursement model, where plan members contribute a certain amount each month that is used to pay for therapies as needed. Cigna takes on the risk, guaranteeing that they will provide as much therapy as the members require.

This model is a great example of how payers can manage the actuarial fluctuation that occurs when funding cell and gene therapies, Trusheim said. But it comes with its challenges, because in some cases, its difficult to ascertain the eligible population for a particular therapy especially if there are alternate therapies already available.

But Trusheim is confident that innovation in reimbursement will catch up to clinical innovation in the precision medicine arena.

Were now in an era where innovation in payment structures and approaches are beginning to match the kind of innovation we have in the transformative science for patients, he said. Successfully providing patient access and benefit requires both kinds of innovation, not just scientific innovation. The creativity is there we are going to succeed. Just as the science has succeeded, the payment innovation is also moving forward and having success.

Photo credit: Devrimb, Getty Images

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Innovative payment models to support cell and gene therapies on the rise - MedCity News

This article was written by Mo Ebrahimkhani, an associate professor of pathology and bioengineering at Pitt,for The Conversation. Faculty members and researchers who want to learn more about publishing in The Conversation canread about the process here.

Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patients cells.

Im a researcher working in this new fieldcalled synthetic biologyfocused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organsfiguring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues.

The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery.

But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical.

Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs.

I am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues.

I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicalslike proteins or sugarin the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation.

To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ.

One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my studentsJeremy Velazquez and Ryan LeGrawused genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells.

The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days.

I and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs.

We then used genetic engineering to tweak genesand the resulting proteinsthat the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tinyseveral millimeters in widthbut more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies.

Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they arent perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.

Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming.

The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bilea chemical important for digestion of food.

When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids designer organoids, as they are generated via a genetic design.

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Genetic Engineering Transformed Stem Cells Into Working Mini-Livers That Extended the Life of Mice With Liver Disease - UPJ Athletics

CAMBRIDGE, Mass., Dec. 7, 2020 /PRNewswire/ --Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced data from six oral and poster presentations highlighted at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. These data demonstrate the company's broad efforts to understand the disease burden, accelerate the diagnosis and transform the treatment of systemic mastocytosis (SM).

"The medical needs in systemic mastocytosis are significant and urgent, and our presentations at the ASH annual meeting demonstrate our efforts to help address these challenges in collaboration with disease experts and the patient community," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "AYVAKIT, an investigational precision therapy for the treatment of SM, is the only potent KIT D816V inhibitor to show a high complete remission rate in advanced SM, as well as improvements in mast cell burden, disease symptoms and quality of life in non-advanced SM. With this foundation of unprecedented clinical data, we continue to build momentum toward bringing AYVAKIT to patients. Later this month, we plan to submit a supplemental new drug application to the FDA for AYVAKIT for advanced SM, and we continue to globally enroll the registrational PIONEER trial for non-advanced SM."

Pure Pathologic Response (PPR) Measures Reduction and Elimination of Mast Cell Burden in Advanced SM, and Significantly Correlates with Improved Overall Survival (OS)

The IWG-MRT-ECNM response criteria (IWG criteria) are the current clinical and regulatory standard for evaluating treatment response in patients with advanced SM, and are primarily based on the resolution of organ damage. With the development of a potent and selective KIT D816V inhibitor, new PPR criteria were established by global SM experts in collaboration with Blueprint Medicines to measure objective reductions and elimination of neoplastic mast cells at the pathological and molecular level. These assessments are used in routine clinical practice, making the criteria more practical in the real-world setting.

In the Phase 1 EXPLORER trial, 53 patients with advanced SM were treated with AYVAKIT and evaluable for response per modified IWG criteria as of a data cutoff of May 27, 2020. The overall response rate (ORR) was 75 percent, and the rate of complete remission with full or partial hematologic recovery (CR/CRh) was 36 percent per modified IWG criteria, consistent with previously reported data. In the same population, the ORR was 77 percent and the CR/CRh rate was 47 percent per PPR criteria. Twenty-five percent of patients had a molecular CR/CRh, with no measurable evidence of residual KIT D816V mutation in the blood or bone marrow. Importantly, patients with a PPR response at six months had significantly improved OS (p=0.013). In the EXPLORER trial, AYVAKIT was generally well-tolerated, and safety data were consistent with previously reported results.

"For patients with advanced systemic mastocytosis, our primary treatment goals are to rapidly reduce their mast cell burden, improve quality of life, and importantly, prolong survival," said Jason Gotlib, M.D., M.S., Professor of Medicine, Hematology, at the Stanford Cancer Institute and an investigator on the EXPLORER trial. "To advance clinical research, it is important to establish objective measures of response that correlate with clinically significant outcomes and can be broadly incorporated into medical practice. The development of pure pathologic response criteria is a promising approach for assessing treatment response to avapritinib and its impact on survival, and clinically validates the role of KIT D816V inhibition in advanced mast cell disease."

Highly Sensitive Blood-Based Droplet Digital Polymerase Chain Reaction (ddPCR) Test Detects KIT D816V Mutation in 95% of Patients

Registry data have shown a median delay of nine years from symptom onset to diagnosis in patients with non-advanced SM,1 highlighting the need for new diagnostic tools.

In Part 1 of the PIONEER trial of AYVAKIT in patients with non-advanced SM, the sensitivity of ddPCR and next-generation sequencing (NGS) KIT D816V testing was evaluated. As of a data cutoff of December 27, 2019, in all 39 enrolled patients who received testing, a blood-based ddPCR test identified the KIT D816V mutation in 95 percent of patients, compared to 28 percent of patients evaluated by an NGS test performed on bone marrow aspirates. In addition, the ddPCR-based KIT D816V test was more sensitive compared to measurements of serum tryptase (77 percent) and bone marrow mast cells (90 percent) using standard World Health Organization diagnostic criteria. These results highlight the clinical value of blood-based, ddPCR-based KIT D816V testing as a confirmatory diagnostic tool to facilitate identification of patients with non-advanced SM, and a non-invasive screening tool for identifying patients with suspected advanced SM that requires a confirmatory bone marrow biopsy.

SM Patients Reported Worse Physical Functioning and Mental Health Compared to Historical Data for Patients with Lung and Colorectal Cancer

SM is characterized by unpredictable, severe and life-threatening complications despite best supportive care. To better understand the burden of disease, Blueprint Medicines is collaborating with clinical experts on the TouchStone survey, a study of adults with SM (n=56), and allergists/immunologists (n=60) and hematologists/oncologists (n=59) who care for patients with SM.

The TouchStone survey showed that SM symptoms have a profound impact on patients' daily functioning, mental health, and ability to work or perform usual activities. Compared to prior research on colorectal and lung cancer patients, participants reported worse physical functioning and mental health based on the 12-item Short Form Survey (SF-12) questionnaire, a valid and widely used health status measure. More than half of patients (54 percent) reported reduced hours at work, and 32 percent filed for medical disability due to their SM. Respondents cited the use of multiple over-the-counter and prescription medications, and frequent visits to physician specialists and the emergency department to manage their SM. In a one-year period, 30 percent of participants reported going to the emergency room at least once for anaphylaxis.

Healthcare providers broadly recognized the high disease burden in SM. A majority reported that non-advanced SM patients under their care feel depressed or discouraged, and limit their activities due to pain or discomfort. For healthcare providers, the most important treatment goals for advanced and non-advanced SM are improved progression-free survival and OS, and better quality of life.

Copies of Blueprint Medicines data presentations from the ASH annual meeting are available in the "SciencePublications and Presentations" section of the company's website at http://www.BlueprintMedicines.com.

About SM

SM is a rare disease driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor OS.

Debilitating symptoms associated with SM, including anaphylaxis, maculopapular rash, pruritis, brain fog, fatigue and bone pain, often persist despite treatment with a number of symptomatic therapies. Patients often live in fear of attacks, have limited ability to work or perform daily activities, or isolate themselves to protect against unpredictable triggers. Currently, there are no approved therapies that selectively inhibit D816V mutant KIT.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit http://www.AYVAKIT.com. This medicine is approved in Europe under the brand name AYVAKYT for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation.

AYVAKIT/AYVAKYT is not approved for the treatment of any other indication, including SM, in the U.S. by the FDA or in Europe by the European Commission, or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing AYVAKIT globally for the treatment of advanced and indolent SM. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of AYVAKIT in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for AYVAKIT in the rest of the world.

AboutBlueprint Medicines

Blueprint Medicinesis a precision therapy company striving to improve human health. With a focus on genomically defined cancers, rare diseases and cancer immunotherapy, we are developing transformational medicines rooted in our leading expertise in protein kinases, which are proven drivers of disease. Our uniquely targeted, scalable approach empowers the rapid design and development of new treatments and increases the likelihood of clinical success. We have two approved precision therapies and are currently advancing multiple investigational medicines in clinical and pre-clinical development, along with a number of earlier-stage research programs. For more information, visit http://www.BlueprintMedicines.comand follow us on Twitter(@BlueprintMeds) andLinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding plans, timelines and expectations for interactions with the FDA and other regulatory authorities; plans and timelines for submitting a supplemental new drug application to the FDA for AYVAKIT for the treatment of advanced SM; expectations regarding the potential benefits of AYVAKIT in treating patients with SM; andBlueprint Medicines'strategy, goals and anticipated milestones, business plans and focus. The words "aim," "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks and uncertainties related to the impact of the COVID-19 pandemic toBlueprint Medicines'business, operations, strategy, goals and anticipated milestones, includingBlueprint Medicines'ongoing and planned research and discovery activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products;Blueprint Medicines'ability and plans in establishing a commercial infrastructure, and successfully launching, marketing and selling current or future approved products, including AYVAKIT and GAVRETO (pralsetinib);Blueprint Medicines'ability to successfully expand the approved indications for AYVAKIT and GAVRETO or obtain marketing approval for AYVAKIT and GAVRETO in additional geographies in the future; the delay of any current or planned clinical trials or the development ofBlueprint Medicines'current or future drug candidates;Blueprint Medicines'advancement of multiple early-stage efforts;Blueprint Medicines'ability to successfully demonstrate the safety and efficacy of its drug candidates and gain approval of its drug candidates on a timely basis, if at all; the pre-clinical and clinical results forBlueprint Medicines'drug candidates, which may not support further development of such drug candidates; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials;Blueprint Medicines'ability to develop and commercialize companion diagnostic tests for its current and future drug candidates; and the success ofBlueprint Medicines'current and future collaborations, partnerships or licensing arrangements, includingBlueprint Medicines'global collaboration with Roche for the development and commercialization of GAVRETO. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" inBlueprint Medicines'filings with theSecurities and Exchange Commission(SEC), includingBlueprint Medicines'most recent Annual Report on Form 10-K, as supplemented by its most recent Quarterly Report on Form 10-Q and any other filings thatBlueprint Medicineshas made or may make with theSECin the future. Any forward-looking statements contained in this press release representBlueprint Medicines'views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law,Blueprint Medicinesexplicitly disclaims any obligation to update any forward-looking statements.

Reference

1Jennings SV, Slee VM, Zach, RM, et al. Patient Perceptions in Mast Cell Disorders. Immunol Allergy Clin North Am. 2018;38(3):505-525.

Trademarks

Blueprint Medicines, AYVAKIT, AYVAKYT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation.

SOURCE Blueprint Medicines Corporation

http://www.blueprintmedicines.com

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Blueprint Medicines Data Presented at 62nd ASH Annual Meeting and Exposition Highlight Broad Commitment to Advance Patient Care in Systemic...

NEW YORK, Dec. 10, 2020 (GLOBE NEWSWIRE) -- BeyondSpring (the Company or BeyondSpring) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced the new data from its Phase 3 PROTECTIVE-2 Study 106 demonstrating that plinabulin in combination with pegfilgrastim offers greater protection against chemotherapy-induced neutropenia (CIN) than the standard of care, pegfilgrastim alone. The study not only met the primary and key secondary objectives, as previously disclosed on Nov. 16, 2020, but also demonstrated that the combination was 53% more effective than pegfilgrastim alone in reducing the incidence of profound neutropenia (absolute neutrophil count or ANC < 0.1 x 10E9 cells/L), 21.6% vs. 46.4%, respectively, p=0.0001, in patients with breast cancer undergoing chemotherapy with TAC (docetaxel, doxorubicin, and cyclophosphamide). Profound neutropenia (PN) is a well-known risk factor to increase the rates of infection, febrile neutropenia (FN), and hospitalization among patients undergoing chemotherapy. Of clinical importance, the combination has shown to reduce the odds of having FN by 41% in comparison to pegfilgrastim, based on reduction of profound neutropenia.

It is clinically meaningful to reduce FN risk by 41% in the combination, compared to pegfilgrastim alone, which is the only major breakthrough advancement in CIN prevention in the last 30 years. The CIN protection from plinabulin added to pegfilgrastim, particularly in the first week of chemotherapy when 75% of CIN-related complications occur before the effect of pegfilgrastim kicks-in in Week 2, fills the treatment gap in current standard of care, said Douglas Blayney, M.D., Professor of Medicine at Stanford Medical School, and global PI for the plinabulin CIN studies. The combination of plinabulin with pegfilgrastim represents a major advancement in offering protection against CIN, with the potential to reduce FN risk, in the care of cancer patients.

The data were presented via a poster at the 2020 San Antonio Breast Cancer Symposium (SABCS): Superior and Clinically Meaningful Protection Against Profound Neutropenia with the Plinabulin/Pegfilgrastim (Plin/Peg) Combination versus Peg In Breast Cancer Patients ReceivingTAC Chemotherapy. Profound neutropenia, an exploratory endpoint representing the most severe form of CIN, is associated with significant risk to patients and may require antibacterial or antifungal prophylaxis [Flowers JCO 2013]. It is attributed to both febrile neutropenia (48%) and infection (50%) [Bodey Cancer 1978]. In BeyondSprings PROTECTIVE-2 studies, patients with profound neutropenia had close to nine times the risk of FN compared to patients with no profound neutropenia. The new data presented at SABCS included:

This trial is a global, multicenter, randomized, double-blinded study in patients with breast cancer undergoing myelosuppressive chemotherapy with TAC (docetaxel at 75 mg/m2, doxorubicin at 50 mg/m2, and cyclophosphamide at 500 mg/m2) for the evaluation of protection against CIN, comparing plinabulin (40 mg) in combination with pegfilgrastim (6 mg) in 111 patients to pegfilgrastim alone (6 mg) in 110 patients. On Day 1, they received TAC and plinabulin or placebo, and on Day 2, they received pegfilgrastim. Topline data from the Protective-2 Phase 3 trial were reported on November 16, 2020 highlighting that the study met its primary endpoint as well as key secondary endpoints.

It is well recognized that CIN is directly related to chemotherapys ability to kill rapidly dividing cells. Unfortunately, fast dividing neutrophils in the bone marrow are adversely affected regardless of the chemotherapy type. As a result, we believe these outcomes are universally applicable to any chemotherapy, and are independent of cancer types, added Gordon Schooley, Ph.D., BeyondSprings Chief Regulatory Officer. As both the U.S. FDA and China NMPA recently awarded BeyondSprings Plinabulin CIN program with Breakthrough Therapy Designation status based on the interim phase 3 data of PROTECTIVE-2, and the Company now completing the PROTECTIVE-2 trial with positive and consistent results to the interim, we are well on track to submit our NDA for CIN in Q1 2021. The improved CIN prevention benefit of the Plinabulin/G-CSF combination would have the potential for CIN prevention of the myelosuppressive effects of different chemotherapeutic agents in millions of patients with multiple tumor types.

Ramon Mohanlal, M.D., Ph.D., BeyondSprings Chief Medical Officer and Executive Vice President, Research and Development concluded, Plinabulin represents a new treatment paradigm for CIN prevention, an area wherein G-CSF has established efficacy, but with short-comings due to its delayed onset of action, next day dosing requirement, bone pain induction, and platelet count reduction. Plinabulin has a fast onset mechanism of action, without causing relevant bone pain or thrombocytopenia, and can be given on the same day as chemotherapy. Plinabulin added to G-CSF offers superior prevention of CIN, and has the potential to avoid life-threatening infections and to improve short-term and long-term survival. Plinabulins anticancer activity from its immune-enhancing mechanism of action, together with its CIN preventive effects, has the potential to become a universal add-on to anti-cancer treatments in general.

The above data are available on BeyondSpringswebsite in the Posters section.

About PlinabulinPlinabulin, BeyondSprings lead asset, is a differentiated immune and stem cell modulator. Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia (CIN). The durable anticancer benefits of Plinabulin have been associated with its effect as a potent antigen-presenting cell (APC) inducer (through dendritic cell maturation) and T-cell activation (Chem and Cell Reports, 2019). Plinabulins CIN data highlight the ability to boost the number of hematopoietic stem / progenitor cells (HSPCs), or lineage-/cKit+/Sca1+ (LSK) cells in mice. Effects on HSPCs could explain the ability of Plinabulin not only to treat CIN, but also to reduce chemotherapy-induced thrombocytopenia and increase circulating CD34+ cells in patients.

About CINPatients receiving chemotherapy typically develop chemotherapy-induced neutropenia (CIN), a severe side effect that increases the risk of infection with fever (also called febrile neutropenia, or FN), which necessitates ER/hospital visits. The updated National Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylactic G-CSFs, such as pegfilgrastim, to include not only high- risk patients (chemo FN rate>20%), but also intermediate-risk patients (FN rate between 10-20%) to avoid hospital/ER visits during the COVID-19 pandemic. The revision of the NCCN guidelines effectively doubles the addressable market of patients who may benefit from treatment with plinabulin, if approved, to approximately 440,000 cancer patients in the U.S. annually. Plinabulin is designed to provide protection against the occurrence of CIN and its clinical consequences in week 1, for early onset of action after chemotherapy. CIN is the primary dose-limiting toxicity in cancer patients who receive chemotherapy treatment.

About BeyondSpringBeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative cancer therapies. BeyondSprings lead asset, plinabulin, a first-in-class agent as an immune and stem cell modulator, is in a Phase 3 global clinical trial as a direct anticancer agent in the treatment of non-small cell lung cancer (NSCLC) and Phase 3 clinical programs in the prevention of CIN. The U.S. FDA granted Breakthrough Therapy designation to plinabulin for concurrent administration with myelosuppressive chemotherapeutic regimens in patients with non-myeloid malignancies for the prevention of chemotherapy-induced neutropenia (CIN). BeyondSpring has strong R&D capabilities with a robust pipeline in addition to plinabulin, including three immuno-oncology assets and a drug discovery platform using the protein degradation pathway, which is being developed in a subsidiary company, Seed Therapeutics, Inc. The Company also has a seasoned management team with many years of experience bringing drugs to the global market. BeyondSpring is headquartered in New York City.

Cautionary Note Regarding Forward-Looking StatementsThis press release includes forward-looking statements that are not historical facts. Words such as "will," "expect," "anticipate," "plan," "believe," "design," "may," "future," "estimate," "predict," "objective," "goal," or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring's current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company's future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet our expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSprings most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law.

Media Contacts

Investor Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 617-430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, Ph.D.LifeSci Communications+1 646-627-8387darren@lifescicomms.com

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BeyondSpring Announces New Positive PROTECTIVE-2 Phase 3 Registrational Trial Results at the 2020 San Antonio Breast Cancer Symposium - BioSpace

MISSISSAUGA, ON, Dec. 10, 2020 /CNW/ -Gilead Sciences Canada, Inc. (Gilead Canada) announced today that YESCARTA(axicabtagene ciloleucel) is now available in Ontario as a treatment for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.i YESCARTA will be manufactured by Kite, a Gilead Company (Kite) at its commercial manufacturing facility in El Segundo, California.

YESCARTA is a chimeric antigen receptor T-cell (CAR T) therapy, an individualized method of treatment that harnesses the power of the body's own immune system to target cancer cells. In CAR T therapy, T cells (a type of white blood cell) are removed from a patient (a process called apheresis) and modified so they can recognize and respond to a specific antigen, which is identified on cancer cells and signals cell death.ii This cell therapy can induce a complete response (no detectable cancer) in a proportion of patients with relapsed or refractory DLBCL and PMBCL, which are aggressive forms of non-Hodgkin lymphoma (NHL).iii Eligible patients in Ontario now have the option to be treated with YESCARTA at Princess Margaret Cancer Centre and The Ottawa Hospital.

"Today's announcement means that patients now have a much-needed new treatment option, which offers an exciting and innovative way to treat these types of blood cancer," saidMelissa Koomey, Vice President and General Manager, Gilead Canada. "Gilead will continue to work to provide final site certification to a number of specialized centres across Canada enabling them to make YESCARTA available to appropriate patients."

DLBCL is the most common form of NHL (a group of cancers that originate primarily in types of white blood cells)iv and accounts for approximately 30 per cent of newly diagnosed cases.v Based on previous rates of diagnosis, in Canada it is estimated that up to 4,000 new cases of DLBCL were diagnosed in 2019.vi,vii The prognosis for relapsed or refractory adult patients is very poor, with a median survival of just six months.viiiGilead Canada received approval for YESCARTA in Canada in February, 2019.

"CAR T therapy is a personalized treatment option that could offer a significant benefit to patients with certain rare and aggressive forms of relapsed or refractory non-Hodgkin lymphoma," said Dr. John Kuruvilla, MD, FRCPC, ZUMA-1 Investigator and Hematologist in the Division of Medical Oncology and Hematology at the Princess Margaret Cancer Centre. "For these patients, the prognosis is very poor, even a year or less. With access to YESCARTA, they have a new andpotentially life changing opportunity."

The approval of YESCARTA was based on one-year follow-up data (median of 15.4 months) from the pivotal ZUMA-1 trial of axicabtagene ciloleucel in adult patients with refractory large B-cell lymphoma. Data from the two-year (median of 27.1 months) follow-up of ZUMA-1 showed that 74 per cent (n=75/101) of adult patients with relapsed or refractory large B-cell lymphoma treated with a single infusion of YESCARTA responded to therapy, with 54 per cent achieving a complete response.ix

In the ZUMA-1 trial the most common Grade 3 or higher adverse reactions include encephalopathy (30%), unspecified pathogen infection (19%), hypotension (15%), fever (14%), cytokine release syndrome (12%), hypoxia (10%), bacterial infection (8%), aphasia (7%), arrhythmia (6%), viral infection (6%), delirium (6%), and hypertension (6%).xGrade 3 or higher prolonged cytopenias (still present at Day 30 or with an onset at Day 30 or beyond) included neutropenia (31%), thrombocytopenia (27%), and anemia (17%).xi

"Today's announcement offers new hope for patients with certain types of relapsed and refractory lymphomas, who previously faced a dire prognosis," said Antonella Rizza, CEO at Lymphoma Canada. "By taking this step, the Ontario government is ensuring Canadians in this province have access to this new and potentially transformative treatment option."

In the ZUMA-1 pivotal trial, Kite demonstrated a 99 per cent manufacturing success rate with a median manufacturing turnaround time of 17 daysxii.

Important Safety InformationThe YESCARTA Product Monograph has aSERIOUS WARNINGS AND PRECAUTIONS BOX regarding the risks of:

YESCARTA should be administered by experienced health professionals at specialized treatment centres.xv

For all important safety information for YESCARTA, including contraindications, warnings and precautions, adverse reactions and drug interactions, please see the Canadian Product Monograph at http://www.gilead.ca.

About Kite Kite, a Gilead Company, is a biopharmaceutical company based in Santa Monica, California. Kite is engaged in the development of innovative cancer immunotherapies. The company is focused on chimeric antigen receptor and T cell receptor engineered cell therapies. For more information on Kite, please visit http://www.kitepharma.com.

About Gilead Sciences Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California. Gilead Sciences Canada, Inc. is the Canadian affiliate of Gilead Sciences, Inc., and was established in Mississauga, Ontario, in 2006. For more information on Gilead Sciences, please visit the company's website at http://www.gilead.com.

Forward-Looking StatementThis press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk thatphysicians and patients may not see the benefits of YESCARTAas a treatment option for the indications for which it is approved; the ability to provide final site certification to specialized centres across Canada enabling them to make YESCARTA available to appropriate patients in the anticipated timelines or at all;the ability of Kite to continue to manufacture YESCARTA at the success rates experienced during clinical trials; and the possibility of unfavorable results from ongoing and additional clinical trials involving YESCARTA. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter endedSeptember 30, 2020 as filed with theU.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

YESCARTA, KITE PHARMA and the KITE LOGO, are trademarks of Kite Pharma, Inc. GILEAD, and the GILEAD LOGO are trademarks of Gilead Sciences, Inc., or its related companies.

Learn more about Gilead at http://www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. For more information on Kite, please visit the company's website atwww.kitepharma.com. Follow Kite on social media on Twitter (@KitePharma) and LinkedIn.

_________________

i YESCARTAproduct monograph, February 13, 2019, revised March 18, 2020 (www.gilead.ca).

iiLeukemia & Lymphoma Society (LLS). Chimeric antigen receptor (CAR) T-cell therapy. 2019. Available at: https://www.lls.org/treatment/types-of-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy. Accessed March 2020.

iii Locke F. et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. The Lancet Oncol. 2019 Jan; 20(1):31-42.

iv Lymphoma Research Foundation (LRF). Diffuse Large B-Cell Lymphoma (DLBCL). 2018. Available at: https://lymphoma.org/wp-content/uploads/2018/05/LRF_FACTSHEET_DIFFUSE_LRG_BCELL_LYMPHOMA_DLBCL.pdf. Accessed March 2020.

v Menon M. et al. The Histological and Biological Spectrum of Diffuse Large B-cell Lymphoma in the WHO Classification. Cancer J. 2012 Sept;18(5):411420.

vi Menon M. et al. The Histological and Biological Spectrum of Diffuse Large B-cell Lymphoma in the WHO Classification. Cancer J. 2012 Sept;18(5):411420.

viiCanadian Cancer Society: Non-Hodgkin Lymphoma statistics. Available at: https://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/statistics/?region=on Accessed March 2020

viii Crump M. et al, Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017 Oct. 130(16): 18001808.

ix YESCARTAproduct monograph, February 13, 2019, revised March 18, 2020 (www.gilead.ca).

xIBID

xi IBID

xii Neelapu, SS, Locke, FL, Bartlett, NL, et al. New England Journal of Medicine. "Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma." Available at: http://www.bloodjournal.org/content/130/16/1800 https://www.nejm.org/doi/full/10.1056/NEJMoa1707447/. Accessed: May 14, 2020.

xiii YESCARTAproduct monograph, February 13, 2019, revised March 18, 2020 (www.gilead.ca).

xiv IBID

xv IBID

SOURCE Gilead Sciences Canada, Inc.

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Kite's YESCARTA (Axicabtagene Ciloleucel) Reimbursed in Ontario for the Treatment of Certain Types of Aggressive Non-Hodgkin Lymphoma - BioSpace