Category Archives: New Jersey Stem Cells

An experimental form of gene therapy developed by a team of researchers from UCLA and Great Ormond Street Hospital in London has successfully treated 48 of 50 children born with a rare and deadly inherited disorder that leaves them without an immune system.

Severe combined immunodeficiency due to adenosine deaminase deficiency, or ADA-SCID, is caused by mutations in the ADA gene that creates the enzyme adenosine deaminase, which is essential to a functioning immune system. For children with the condition, even day-to-day activities like going to school or playing with friends can lead to dangerous, life-threatening infections. If untreated, ADA-SCID can be fatal within the first two years of life.

The investigational gene therapy method involves first collecting some of the childs blood-forming stem cells, which have the potential to create all types of blood and immune cells. Next, using an approach developed by the research team, a new copy of the ADA gene is delivered into the stem cells by a modified lentivirus, or viral vector. The corrected cells are then returned to the childs body, where they are intended to produce a continual supply of healthy immune cells capable of fighting infection.

In a studypublished today in the New England Journal of Medicine, co-lead authors Dr. Donald Kohn of UCLA and Dr. Claire Booth of Great Ormond Street Hospital, or GOSH, report two- and three-year outcomes for children treated with the investigational lentiviral gene therapy in clinical trials at GOSH, UCLA Mattel Childrens Hospital and the National Institutes of Health between 2012 and 2017.

Between all three clinical trials, 50 patients were treated, and the overall results were very encouraging, said Kohn, a distinguished professor of microbiology, immunology and molecular genetics and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. All the patients are alive and well, and in more than 95% of them, the therapy appears to have corrected their underlying immune system problems.

No complications or treatment-limiting events were reported among the patients. Most adverse events were mild or moderate, and were considered to be related to routine procedures performed in preparation for the experimental gene therapy treatment or effects of the immune system rebuilding.

Treatment was successful in all but two of the 50 cases, and both of those children were able to return to current standard-of care-therapies and treatments, with one eventually receiving a bone marrow transplant, said Kohn, who has been working to develop gene therapies for ADA-SCID and other blood diseases for 35 years.

The investigational gene therapy a one-time procedure that the researchers say may provide lifelong results is a welcome potential new treatment option for children with ADA-SCID, who otherwise must undergo once- or twice-weekly injections of the ADA enzyme until a matched bone marrow donor, usually a close family member, can be found. If a donor is not available, patients require lifelong injections, along with antibiotics, antifungal medications and monthly infusions of immunoglobulin, which contains infection-fighting antibodies. These treatments are expensive and therefore out of reach for patients in many countries.

If approved in the future, this treatment could be standard for ADA-SCID, and potentially many other genetic conditions, removing the need to find a matched donor for a bone marrow transplant and the toxic side effects often associated with that treatment, said Booth, a GOSH consultant inpediatric immunology and genetherapy.

The benefits of lentiviral gene therapy

Prior to teaming up, both Booth and Kohn worked separately for years onsuccessful gene therapiesfor ADA-SCID that used viral vectors made from retroviruses. Retroviral vectors, however, can only enter cells nuclei to deliver genes while the cells are dividing, limiting the number of cells receiving the genetic payload and, thereby, the potential efficacy of the treatment.

Additionally, while neither Kohn nor Booth observed serious complications in their ADA-SCID trials, other earlier studies testing retroviral vector-based gene therapies did report some serious side effects, including leukemia, in some patients.

In 2008, Booth and Kohn began collaborating with professors Bobby Gaspar and Adrian Thrasher of University College London to develop an improved viral vector using a different kind of virus, called a lentivirus. Viruses of this kind can enter non-dividing cells nuclei and, when used as vectors, have the potential to make gene therapies safer and more effective. ADA-SCID patients began receiving the new gene therapy at GOSH in 2012; the following year, the experimental treatment was offered at UCLA and the NIH.

More than 200 patients with various genetic conditions across the worldhave now been treatedwith experimental lentiviral gene therapies, and applying gene therapy to ADA-SCIDis another significantscientific advance, said Thrasher, a senior author of the study who is also a professor of pediatric immunology at GOSH.

Ten of the children in the UCLA study were treated using a frozen preparation of corrected stem cells. These children experienced similar outcomes to the children treated with cells that were not frozen. The freezing approach may allow children with ADA-SCID to have their stem cells collected locally, then have them transported and processed at a manufacturing facility elsewhere and shipped back to a specialized hospital near them, removing the need for patients and their families to travel long distances to specialist centers.

One patients story: A life-changing treatment

Courtesy of Chelsea Oakley

One of the patients who received a frozen preparation of cells at UCLA, Cora Oakley of Morristown, New Jersey, was diagnosed with ADA-SCID through newborn genetic screening at just 7 days old, in April 2017.I remember asking the doctor if my daughter was going to die, Coras mother, Chelsea Oakley, said of receiving the diagnosis. And his response was, I hope not. It was the darkest day of my life.

Cora was the last child to enroll in the clinical trial and received her own corrected cells in September 2017.Following the gene therapy, Cora and her family spent a month in the bone marrow transplant unit of a hospital closer to their home for Coras follow-up treatment. The experiences of the other young patients in this unit opened Oakleys eyes to what her daughter would have gone through if the experimental gene therapy hadnt been an option.

I saw young bone marrow transplant patients who developed graft-versus-host disease and others who had to take all these anti-rejection medications and still had issues. I just thought no one should have to suffer like this, she said. And then heres my daughter who had this life-changing treatment that felt like a miracle. It still shocks me all the time how unbelievably fortunate we are.

Now a healthy and exuberant 4-year-old, Cora is described by her mom as a rough and tumble, outdoors kind of kid who loves all animals and is incredibly social. Ill never forget what it felt like when we didnt know if shed ever be able to do any of these things, Oakley said.

The investigational lentiviral gene therapy is licensed to Orchard Therapeutics and has not been approved for clinical use by any regulatory authority.

The research was funded by the National Institute of Allergy and Infectious Diseases, the National Heart, Lung and Blood Institute, and the National Human Genome Research Institute (all part of the U.S. National Institutes of Health); the California Institute for Regenerative Medicine; the U.K. National Institute for Health Researchs Biomedical Research Centre at Great Ormond Street Hospital for Children National Health Service Foundation Trust, University College London and Orchard Therapeutics.

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Gene therapy offers potential cure to children born without an immune system - UCLA Newsroom

When Ashley Hopkins walks across the stage Wednesday during a commencement ceremony at Rowan University, she will be sharing it with her brother thousands of miles away.

Brett Hopkins is deployed overseas with the New Jersey National Guard Air Force but Ashley will symbolically accept his diploma for a bachelors degree in finance, magna cum laude. She has also earned a degree from the William G. Rohrer College of Business.

I wasnt going to walk because I have one more semester for my double major in human resources, Ashley said during an interview with NJ Advance Media. But I still have enough credits for the degree now. Were both first-generation for a degree in our family and I know its something that makes my mother really proud.

The Hopkins are among a group of standout graduates singled out by Rowan during this commencement. Others include Katherine Trauger, who is headed to the University of Oxford, London, on a full scholarship for a Masters Degree and Gatha Adhikari, who survived a deadly earthquake in Nepal in 2015 and now has a bachelors degree in biomedical engineering. She is on her way to the University of Maryland for a masters and doctoral program.

Brett Hopkins, 23, sent a video and a photo of him accepting his diploma cover at an undisclosed location overseas. It is scheduled to be featured during some of the 20 socially-distanced commencement ceremonies over four days on Saturday, Monday, Wednesday and Thursday.

He is a year older than Ashley but began college a year later. Both commuted from the Sicklerville section of Gloucester Township to Rowans main campus in Glassboro some 9 miles away.

About half of Rowans 19,000 students are commuters. The remainder live on or near the 800-acre Glassboro campus.

I did my first two years at Camden County College, Ashley said. I didnt need the full college experience. I dont think there is anything wrong with that. Everyone can have a different education and still have a good outcome.

Ashley Hopkins, right, accepted her and her brother's diploma covers during a commencement ceremony Wednesday at Rowan University, N.J. Brett Hopkins, her brother, abroad for a N.J. Air National Guard deployment.

Ashley aspires to work in human resources and is completing an internship now with an office products company. She is not sure what her brother plans to do after his deployment but said he was recently promoted to lieutenant.

Katherine Trauger, 22, of Cherry Hill, said Rowan was her safe school when she was applying to colleges. She initially wanted to pursue a career in music. Her mother is a professional opera singer and she thinks spending hours at her rehearsals when she was a child helped shape her world view.

But she decided to attend Rowan and pursue history and political science instead. Her commencement ceremony will be held Thursday.

My mother has always told me to go for it, reach for the stars, she said. Ive always been adventurous.

But she also proved to be practical. She said she couldnt turn down the scholarship package from Rowan. She also quickly learned her instructors inspired her to do great things, like dream of going abroad to attend one of the most prestigious universities in the world.

I have a professor from the history department who went to Oxford to get his degree, Trauger said. He had kind of been my mentor and was always saying you can do this Katherine you can go to the London school of economics. All along I was saying its just not possible. Its just not going to happen.

But it did.

Trauger said she plotted a path forward. It included getting published, volunteering for campaign work with local politicians and getting hired to work at a policy think tank in Philadelphia.

Kathrine Trauger graduated with a bachelor's degree in history and political science from Rowan University on Thursday.

On a whim, I sent my resume into the Foreign Policy Research Institute in Philadelphia and this man Clint Watts, a political commentator and researcher on MSNBC, emailed me. He saw my resume and thought I would be a great fit.

Watt, also a former FBI agent, is working on a study on foreign intervention in the U.S. election.

I joined this research team with kids from Harvard, Yale, Stanford, Brown and then theres me from Rowan, she said. The key thing was getting myself off campus and finding these experiences. Its a good reminder that people who are going to change the world are coming from these small state schools.

Trauger is preparing to cross an ocean in the fall to continue her academic journey. Gatha Adhikari crossed the same ocean four years ago to begin hers at Rowan.

It has been great, but its kind of bittersweet, Adhikari said during a telephone interview this week as she prepared for her commencement ceremony Monday.

My family could not be here because of COVID, Adhikari said. They are back home in Nepal. Four years ago when I came here I was alone. Today I have friends and support from everyone. I came a long way but it was worth it.

Adhikari said her entire village of Begnastal were planning to watch a live stream of her 1 p.m. ceremony. Nepal is 9 hours and 45 minutes ahead of time in New Jersey. Her village has a total population of about 300, she said. Nepal is a landlocked country in the Himalayas sandwiched between India and the Tibet region of China. Mount Everest is there and the exotic local of Kathmandu.

Back when I was a girl I never dreamed about being here, she said. Biomedical engineering for a little girl seemed impossible. It shows its possible if you believe in yourself.

Adhikari survived a 7.8 richter scale earthquake in Nepal in 2015 that killed nearly 9,000 people and destroyed more than 600,000 structures. She said she was away at school when just about everything came crashing down. Many of the buildings were made of mud and stone and laid in ruins around her. She said they lived outdoors in tents for more than a week and experienced anxious hours afterward until she was able to reach her parents.

That experience helped to shape her future aspirations.

Gatha Adhikari accept her bachelors degree in biomedical engineering this week at Rowan University, N.J.

Thats one of the reasons I decided to go into biomedical research, she said. I felt so helpless after the quake. I thought if I pursued this I would be able to help people.

Adhikaris research at Rowan involves making gels with regenerative stem cells. The research could help regrow skin that has been damaged.

She said she won a Fulbright scholarship when she was in high school in Nepal. That helped her go abroad for school. She chose Rowan because of its engineering program and its affordability.

Now she is a mentor for three male students from Nepal who also attend Rowan.

Im like their mother, she said. I do everything for them. I was like an alien when I first came. I can vibe with the people now. This is my home.

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Bill Duhart may be reached at bduhart@njadvancemedia.com.

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Commencement stories from Rowan paint a picture of opportunities near and far - NJ.com

Increased Need for Blood Donations throughout Monmouth County during Nationwide COVID-19 Surge

MONTVALE, NJ Due to thenationwide surge in COVID-19 infections, along with the usual drop-offin donations at the beginning of the holiday season, theres now a particularly severe blood shortage.

In response, the nonprofit, blood-collection organization Vitalant is providing a local, open-to-the-public donation event on Saturday, December 5 from 8 a.m. to 1 p.m. at the Knights of Columbus, 70 East Main Street, Freehold.

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Individuals who have recovered from COVID-19 are urged to donate blood plasma. Known as convalescent plasma, this blood component contains antibodies that may provide seriously ill patients an extra boost in fighting the disease. There is also a great need for blood platelets small cells in the blood that form clots to prevent bleeding, while also helping with anemia and low blood counts and type O-negative, the universal blood type.

FEMA has specifically identified blood donation as an essential and integral component of the emergency support function. Of note, coronavirus cannot be transferred through the blood. And, as always, the blood collection process is safe with no impact on the donor's immune system. Vitalant staff follows rigorous safety and disinfection protocols at its blood drives and donation centers and have always required individuals to be in good health to donate blood.

Vitalant also maintains four New Jersey blood centers, with hours and street addresses as follows:

Healthy individuals age 16 or older, who weigh at least 110 pounds, may donate blood; 16- and 17-year-olds must have proof of birth date and signed consent forms, either in English (http://www.communitybloodservices.org/media/Minor_Donor_Permit_ENG.pdf) or Spanish (http://www.communitybloodservices.org/media/Minor_Donor_Permit_Form_SP.pdf). Donors should eat a moderate meal prior to donating, and also bring identification featuring their signature.

On occasion, last-minute changes to scheduling for a donation event will occur. As a result, it is recommended that anyone planning to donate blood at a Vitalant donation event call 201-251-3703, toll free, to confirm timing and location details. Additional information about donating blood is also available by visitingwww.vitalant.org.

Vitalant has initiated a multiweek incentive program to attract additional donations at its New Jersey donation centers. Specifics are as follows:

December 23 January 1

All donors will receive a Vitalant T-shirt or 200 bonus pointstoward exclusive rewards through Vitalants online store.

About Vitalant in New Jersey

A not-for-profit organization that supplies blood and blood products to hospitals in the NJ/NY region, Bergen County-based Vitalant (previously Community Blood Services) has been devoted to serving the communitys transfusion medicine needs since 1953. Donations of blood and blood products, umbilical cord blood, stem cells, and bone marrow help to join individuals, organizations, businesses, and entire communities together in partnership to help save lives.

About Vitalant

Arizona-based Vitalant is among the nations oldest and largest transfusion medical organizations in the U.S. Founded in 1943, its blood centers division serves some 700 hospitals across the United States. A founding member of Americas Blood Centers and the AABB (formerly the American Association of Blood Banks), Vitalant also operates biological products distribution services, a quality consulting group, and a world-renowned transfusion medicine research institute. It also is a partner in the operation of high-volume donor testing laboratories.

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Vitalant to Hold Blood Donation Event on December 5 in Freehold - TAPinto.net

SOMERSET, N.J. and NEW YORK, Oct. 22, 2020 (GLOBE NEWSWIRE) -- Catalent (NYSE: CTLT), the leading global provider of advanced delivery technologies, development, and manufacturing solutions for drugs, biologics, cell and gene therapies, and consumer health products, and BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, today announced an agreement for the manufacture of NurOwn, BrainStorms autologous cellular therapy being investigated for the treatment of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease or motor neuron disease.

NurOwn induces mesenchymal stem cells (MSCs) to secrete high levels of neurotrophic factors (NTFs) known to promote the survival of neurons and neuroprotection. The therapy has received Fast Track status from the U.S. FDA for ALS and has also been granted Orphan Drug Status for ALS by both the FDA and the European Medicines Agency. BrainStorm is currently completing a 200-patient, double-blind, placebo-controlled, repeat-dosing NurOwn Phase 3 study in the U.S.

As part of its commitment, Catalent will undertake the transfer of the manufacturing process to, and provide future CGMP clinical supply of NurOwn from, its new, 32,000 square-foot cell therapy manufacturing facility in Houston, Texas. On completion of the clinical trials and in anticipation of potential approval of NurOwn, the companies will look to extend the partnership to include commercial supply from the Houston facility.

We are proud to have a partner in Catalent whose excellence in manufacturing quality therapies will support commercial supply of NurOwn, said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. We know that ALS patients are in urgent need of a new treatment option. If NurOwn is successful in the current clinical trials, this agreement will be integral to ensuring rapid access for patients.

Manja Boerman, Ph.D., President, Catalent Cell & Gene Therapy, said, Our experience in cell therapy development, and the manufacturing capabilities that our newly constructed, state-of-the-art facility in Houston offers, position us to best support BrainStorm, with its leading therapeutic candidate for ALS treatment. We look forward to partnering with BrainStorm and providing our stem cell manufacturing expertise as we work to optimize production and streamline the products path towards commercial launch.

About Catalent Cell & Gene Therapy

With deep experience in viral vector scale-up and production, Catalent Cell & Gene Therapy is a full-service partner for adeno-associated virus (AAV) and lentiviral vectors, and CAR-T immunotherapies. When it acquired MaSTherCell, Catalent added expertise in autologous and allogeneic cell therapy development and manufacturing to position it as a premier technology, development and manufacturing partner for innovators across the entire field of advanced biotherapeutics. Catalent has a global cell and gene therapy network of dedicated, large-scale clinical and commercial manufacturing facilities, and fill-finish and packaging capabilities located in both the U.S. and Europe. An experienced partner, Catalent Cell & Gene Therapy has worked with industry leaders across 70+ clinical and commercial programs.

About Catalent

Catalent is the leading global provider of advanced delivery technologies, development, and manufacturing solutions for drugs, biologics, cell and gene therapies, and consumer health products. With over 85 years serving the industry, Catalent has proven expertise in bringing more customer products to market faster, enhancing product performance and ensuring reliable global clinical and commercial product supply. Catalent employs approximately 14,000 people, including around 2,400 scientists and technicians, at more than 45 facilities, and in fiscal year 2020 generated over $3 billion in annual revenue. Catalent is headquartered in Somerset, New Jersey. For more information, visit http://www.catalent.com

More products. Better treatments. Reliably supplied.

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also received U.S. FDA acceptance to initiate a Phase 2 open-label multicenter trial in progressive MS and enrollment began in March 2019.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment inAugust 2020. For more information, visit the company's website at http://www.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorm's need to raise additional capital, BrainStorm's ability to continue as a going concern, regulatory approval of BrainStorm's NurOwn treatment candidate, the success of BrainStorm's product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorm's NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorm's ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorm's ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

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Catalent and BrainStorm Cell Therapeutics Announce Partnership for the Manufacture of Mesenchymal Stem Cell Platform Therapy NurOwn - GlobeNewswire

Genmab Announces IFM, HOVON and Janssen Achieve Positive Topline Results in Second Part of Phase 3 CASSIOPEIA Study of Daratumumab in Multiple Myeloma at Pre-planned Interim Analysis

Company Announcement

Copenhagen, Denmark; October 21, 2020 Genmab A/S (Nasdaq: GMAB) announced today positive topline results from the second part of the Phase 3 CASSIOPEIA (MMY3006) study of daratumumab monotherapy as maintenance treatment versus observation (no treatment) for patients with newly diagnosed multiple myeloma eligible for autologous stem cell transplant (ASCT). The second part of the study, which is being conducted by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Research & Development, LLC (Janssen), met the primary endpoint of improving progression free survival (PFS) at a pre-planned interim analysis (Hazard Ratio (HR) = 0.53 (95% CI 0.42 0.68), p < 0.0001) resulting in a 47% reduction in the risk of progression or death in patients treated with daratumumab. The safety profile observed in this study was consistent with the known safety profile of daratumumab and no new safety signals were observed.

Based on the results at the pre-planned interim analysis conducted by an Independent Data Monitoring Committee (IDMC), it was recommended to unblind the study results. Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, plans to discuss the potential for a regulatory submission for this indication with health authorities, and plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.

Following the positive data from the first part of the CASSIOPEIA study, we are very pleased to see this benefit. We are appreciative of the efforts of the IFM, of HOVON and of Janssen for their work on this study, said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

About the CASSIOPEIA (MMY3006) StudyThis Phase 3 study is a randomized, open-label, multicenter study, conducted by the IFM in collaboration with the HOVON and Janssen, which includes 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who were eligible for high dose chemotherapy and ASCT. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide and dexamethasone (VTd) or VTd alone. The primary endpoint was the number of patients that achieved a stringent complete response (sCR). In the second part of the study, patients that achieved a response underwent a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival.

About Multiple MyelomaMultiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX (daratumumab)DARZALEX (daratumumab) has become a backbone therapy in the treatment of multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who have received one to three previous lines of therapy; in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma.

DARZALEX is indicated for the treatment of adult patients in Europe via intravenous infusion or subcutaneous administration: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy7. Daratumumab is the first subcutaneous CD38 antibody approved in Europe for the treatment of multiple myeloma. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S.

In Japan, DARZALEX intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. For more information, visit http://www.DARZALEX.com.

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, is approved in the United States for the treatment of adult patients with multiple myeloma: in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for ASCT; in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for ASCT and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy; in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy; and as monotherapy, in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.8 DARZALEX FASPRO is the first subcutaneous CD38 antibody approved in the U.S. for the treatment of multiple myeloma.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a persons own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,9,10,11,12

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase 3 studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis and T-cell acute lymphocytic leukemia (ALL). Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

About Genmab Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. Founded in 1999, the company is the creator of the following approved antibodies: DARZALEX (daratumumab, under agreement with Janssen Biotech, Inc.) for the treatment of certain multiple myeloma indications in territories including the U.S., Europe and Japan, Kesimpta (subcutaneous ofatumumab, under agreement with Novartis AG), for the treatment of adults with relapsing forms of multiple sclerosis in the U.S. and TEPEZZA (teprotumumab, under agreement with Roche granting sublicense to Horizon Therapeutics plc) for the treatment of thyroid eye disease in the U.S. A subcutaneous formulation of daratumumab, known as DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) in the U.S., has been approved in the U.S. and Europe for the treatment of adult patients with certain multiple myeloma indications. The first approved Genmab created therapy, Arzerra (ofatumumab, under agreement with Novartis AG), approved for the treatment of certain chronic lymphocytic leukemia indications, is available in Japan and is also available in other territories via compassionate use or oncology access programs. Daratumumab is in clinical development by Janssen for the treatment of additional multiple myeloma indications, other blood cancers and amyloidosis. Genmab also has a broad clinical and pre-clinical product pipeline. Genmab's technology base consists of validated and proprietary next generation antibody technologies - the DuoBody platform for generation of bispecific antibodies, the HexaBody platform, which creates effector function enhanced antibodies, the HexElect platform, which combines two co-dependently acting HexaBody molecules to introduce selectivity while maximizing therapeutic potency and the DuoHexaBody platform, which enhances the potential potency of bispecific antibodies through hexamerization. The company intends to leverage these technologies to create opportunities for full or co-ownership of future products. Genmab has alliances with top tier pharmaceutical and biotechnology companies. Genmab is headquartered in Copenhagen, Denmark with sites in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.

Contact: Marisol Peron, Corporate Vice President, Communications & Investor Relations T: +1 609 524 0065; E: mmp@genmab.com

For Investor Relations: Andrew Carlsen, Senior Director, Investor RelationsT: +45 3377 9558; E: acn@genmab.com

This Company Announcement contains forward looking statements. The words believe, expect, anticipate, intend and plan and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmabs most recent financial reports, which are available on http://www.genmab.com and the risk factors included in Genmabs most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at http://www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab; the Y-shaped Genmab logo; Genmab in combination with the Y-shaped Genmab logo; HuMax; DuoBody; DuoBody in combination with the DuoBody logo; HexaBody; HexaBody in combination with the HexaBody logo; DuoHexaBody; HexElect; and UniBody. Arzerra and Kesimpta are trademarks of Novartis AG or its affiliates. DARZALEX and DARZALEX FASPRO are trademarks of Janssen Pharmaceutica NV. TEPEZZA is a trademark of Horizon Therapeutics plc.

1 American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma.Accessed June 2016.2 National Cancer Institute. "A Snapshot of Myeloma." Available at http://www.cancer.gov/research/progress/snapshots/myeloma. Accessed June 2016. 3 Globocan 2018. United States of America Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/840-united-states-of-america-fact-sheets.pdf.4 Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed December 2018.5 American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 20166 DARZALEX Prescribing information, August 2020 https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761036s029lbl.pdf Last accessed August 20207 DARZALEX Summary of Product Characteristics, available at https://www.ema.europa.eu/en/medicines/human/EPAR/darzalex Last accessed June 20208 DARZALEX FASPRO Prescribing information, May 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761145s000lbl.pdf Last accessed May 20209 De Weers, M et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.10 Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-21.11 Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; 128: 384-94.12 Jansen, JH et al. Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking.Blood. 2012; 120(21): abstract 2974.

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Genmab Announces IFM, HOVON and Janssen Achieve Positive Topline Results in Second Part of Phase 3 CASSIOPEIA Study of Daratumumab in Multiple Myeloma...

As the guardian of the genome and the most frequently mutated gene in human cancer, TP53 and the p53 tumor suppressor protein it encodes make a compelling therapeutic target with the potential for broad-based activity. But p53 presents a significant challenge for investigators, and the field is littered with clinical trial failures and abandoned drug development programs.1,2

This year was shaping up to be a landmark one for this intensively researched cancer drug target, with a hotly anticipated readout from a phase 3 trial of idasanutlin, a small molecule inhibitor of the p53-regulatory protein MDM2.3,4

However, results from the phase 3 MIRROS trial in patients with relapsed/refractory acute myeloid leukemia (AML) proved yet another disappointment5 for a field that has taken more than its fair share of blows over the decades.1,2

Nevertheless, investigators continue to push the boundaries of drug development in their efforts to develop novel p53-targeting agents and potential combinatorial strategies. Several companies are pursuing drugs that reactivate mutant forms of the p53 protein, restoring its tumor-suppressive properties.

One such agent, eprenetapopt (APR-246), received a breakthrough therapy designation in January 2020 for the treatment of patients with TP53-mutant myelodysplastic syndromes (MDS).6 Promising phase 2 data for the drug were highlighted at the 2019 American Society of Hematology Annual Meeting (ASH).7

Discovered more than 4 decades ago,8 the p53 protein is best known for its role as a transcription factor. Modulating the expression of multiple important genes positions p53 as a master regulator of a range of cellular processes, the most thoroughly studied being the DNA damage response.

Levels of p53 protein are generally low; however, in response to cellular stressors such as DNA damage, p53 is activated, accumulates in the nucleus, and induces the expression of genes that contain specific response elements. Among its targets are regulators of the cell cycle, DNA repair, and apoptosis, which allow the cell to pause cycling to repair damaged DNA or induce cell death if the damage is irreparable. In this way, p53 serves as a barrier to the genomic instability that fosters cancer development, earning it the nickname guardian of the genome (FIGURE).2,9-12

The p53 protein is composed of multiple functional domains: Two transactivation domains operate together and independently to mediate the transcription of p53 target genes, a proline-rich domain is implicated in p53-mediated inhibition of cell growth and stimulation of apoptosis, and a DNA-binding domain allows p53 to bind the promoters of target genes.2

In addition, p53 contains an oligomerization domain that enables it to form a homotetramer (required for transcription factor activity), a nuclear export signal, and an unstructured C-terminal domain that is targeted by post-translational modifications that fine-tune p53s activity.2

The activity of p53 is tightly controlled by other mechanisms, most notably by 2 negative regulators, MDM2 and MDM4. MDM2 is an E3 ubiquitin ligase that tags p53 with the small molecule ubiquitin, promoting the removal of p53 from the nucleus and targeting it for degradation by the proteasome.1,2,9,11

Notably, the MDM2 gene is a transcriptional target of p53; thus, a negative feedback loop exists whereby p53 promotes the expression of its own negative regulator. MDM4 does not possess E3 ligase activity but interacts with MDM2 to promote ubiquitination of p53.2

The importance of p53 as a tumor suppressor is reflected in reports that it is mutated in approximately half of all human cancers.2,9,10,12 Its prevalence varies widely across tumor types, reaching up to 95% in high-grade serous ovarian cancer (TABLE 1).13

Somatic TP53 mutations are also extremely common in small cell lung cancer, pancreatic cancer, squamous cell carcinoma of the head and neck, and invasive breast cancer, particularly the triple-negative subtype.14

Meanwhile, germline mutations in TP53 are associated with the rare Li-Fraumeni syndrome, in which individuals have an increased risk of developing cancer over the course of their lifetime.11,12

Although many types of mutation have been identified in TP53, the vast majority occur within the DNA-binding domain, affecting p53s ability to activate its target genes and leading to a loss of tumor- suppressive function.2,12

Interestingly, unlike other tumor suppressor proteins, which are usually affected by deletion or nonsense mutations, most TP53 mutations result in a single amino acid substitution.5 These missense mutations are broadly classified into 1 of 2 types: either contact mutations that directly impede p53s ability to bind target genes DNA or structural mutations that induce a conformational change in the p53 protein that affects its function.2,10,12

Moreover, it is thought that the effect of mutant p53 on carcinogenesis may occur through more than just a passive loss of its tumor-suppressive capabilities. Mutant p53 can also affect wild-type p53 when both forms are present in the same cell. Unlike deletions or nonsense mutations, missense mutations allow the production of full-length (albeit defective) protein. This mutant p53 protein is capable of forming complexes with the wild-type protein that dampen the antitumor functions of the wild-type protein.10,14,15

The mutant form also has been shown to acquire protumorigenic functions through interaction with other proteins that play a role in various cancer hallmarks.2,10,12

Even in the absence of gene mutations, p53 function is often impaired in cancer cells. A major mechanism is through dysregulation of the MDM2 and MDM4 proteins, which are frequently overexpressed in various tumor types. Ultimately, the p53 pathway is thought to be nearly universally dysfunctional in human malignancies, making it an enticing therapeutic target.2,11

For decades, investigators have sought to harness the p53 protein in drug development, but tumor suppressor proteins are notoriously difficult to target and require unconventional therapeutic strategies. A variety of methods are under investigation today, according to a search of ClinicalTrials.gov. These include vaccines and agents with targets that affect p53 functions. One of the most prevalent strategies involves targeting MDM2 protein activity and one of the most innovative seeks to reactivate p53 regulation (TABLE 2).

Among the earliest and most promising approaches to treating tumors without TP53 mutations was the attempt to block the interaction between p53 and its negative regulator MDM2. Targeting protein-protein interactions also holds challenges, but investigators identified a hydrophobic groove on the surface of MDM2 that offered a binding foothold.1,2

The early 2000s saw the emergence of the nutlins, named after the Roche facility in Nutley, New Jersey, where they were discovered.1 The first to advance to clinical trials, RG7112, showed promise in phase 1 studies but was limited by the development of significant gastrointestinal (GI) and hematologic toxicities.1,2,9

Idasanutlin is a more potent and selective nutlin analogue based on a different chemical scaffold.1,3,9 Data from phase 1/2 studies suggested that idasanutlin had clinical activity alone and in combination with other drugs in patients with AML,3 a cancer type in which p53 dysfunction is highly prevalent despite a comparatively low rate of TP53 mutations (5%-8% of newly diagnosed patients; 30%-40% of therapy-related AML).16

Idasanutlin advanced to the phase 3 MIRROS trial, in which it was evaluated in combination with cytarabine compared with cytarabine alone in patients with relapsed/ refractory AML fit for intensive salvage therapy (NCT02545283). However, the MIRROS study was terminated due to futility based on efficacy results at a planned interim analysis, according to an update posted in May 2020 on ClinicalTrials.gov.4

The results of this analysis were presented at the virtual 25th European Hematology Association Congress in June 2020. A total of 447 patients were randomized 2:1 to receive idasanutlin 300 mg (or placebo) twice daily plus cytarabine 1 g/m2 once daily on days 1 to 5 of a single 28-day induction cycle. Responders could follow this with up to 2 optional consolidation cycles of once-daily idasanutlin 300 mg plus cytarabine 1 g/m2.

The study failed to meet its primary end point of improved overall survival (OS); median OS was 8.3 months in the idasanu-tlin arm and 9.1 months for placebo (HR, 1.08; 95% CI, 0.81-1.45; P = .58). Overall response rate (ORR) was 38.8% versus 22.0% (OR, 2.25; 95% CI, 1.36-3.72), and complete response (CR) was achieved in 20.3% and 17.1% of patients, respectively (OR, 1.23; 95% CI, 0.70-2.18).

The most common adverse events (AEs) were GI toxicities, and there were similar rates of grade 3 to 5 AEs in the 2 arms; most commonly, febrile neutropenia, thrombocytopenia, and anemia.5

Several other clinical trials of idasanutlin are ongoing, including a phase 1b study in which idasanutlin is being tested in combination with the BCL-2 inhibitor venetoclax (Venclexta)a combination that has shown potent synergy in preclinical trials in elderly patients with relapsed/ refractory AML who are ineligible for chemotherapy (NCT02670044).

Among 49 patients, there was a 41% anti-leukemic response rate, a measure that encompasses the rates of CR, CR with incomplete platelet count recovery, CR with incomplete hematologic recovery, partial response (PR), and morphologic leukemia- free state. Median duration of response (DOR) was 4.9 months, and median OS was 4.4 months. The most common AEs were diarrhea and nausea, and grade 3 or 4 AEs included febrile neutropenia, neutropenia, and thrombocytopenia.17

Although some companies have suffered setbacks with MDM2 inhibitors, others are persevering; several new agents in this class have entered clinical trials.1 KRT-232 (AMG 232) was originally developed by Amgen, but Kartos Therapeutics has taken over development. The results of a first-in- human clinical trial were recently published (NCT01723020). A total of 107 patients with various advanced solid tumors or multiple myeloma were enrolled, most of whom had received 3 or more prior lines of therapy.

During dose escalation (n = 39), KRT-232 was administered at doses of 15, 30, 60, 120, 240, 300, 360, and 480 mg. There were 3 dose-limiting toxicities (DLTs): grade 3 neutropenia and grade 3 and 4 thrombocytopenia. The highest tolerated dose, 240 mg, was evaluated in dose expansion (n = 68). The most common treatment-related AEs (TRAEs) in the dose-expansion group were diarrhea, nausea, vomiting, fatigue, decreased appetite, and thrombocytopenia, mostly grade 1 or 2 in severity.

Per central evaluation, 4% of patients had unconfirmed PRs (including patients with well-differentiated liposarcoma, squamous cell carcinoma, and breast cancer), whereas most patients experienced stable disease (SD).18 KRT-232 also recently showed limited clinical activity in a phase 1 clinical trial in patients with relapsed/refractory AML (NCT02016729).19

Ascentage Pharma is developing another MDM2 antagonist, APG-115, and a phase 1 study in patients with advanced solid tumors has been completed (NCT02935907). Among 28 patients, who had received a median of 4 prior lines of therapy and were treated with doses ranging from 10 to 300 mg for 21 days of 28-day cycles, 6 patients experienced SD after 2 cycles. The most common AEs included fatigue, nausea, vomiting, diarrhea, decreased appetite, dehydration, neutropenia, leukopenia, pain in extremity, and thrombocytopenia.20

None of the MDM2 inhibitors under evaluation block MDM4 activity, and tumors overexpressing this protein would likely be resistant to these drugs. A dual inhibitor of both MDM2 and MDM4 is therefore desirable, and Aileron Therapeutics has a first-in-class drug, ALRN-6924, in clinical trials. In p53, a helical region binds to both MDM2 and MDM4, and ALRN-6924 is a stapled peptide, locked in a helical conformation that mimics this region.21,22 It is being evaluated in several ongoing phase 1 clinical trials.

Aileron is also exploring ALRN-6924 as a chemoprotectant. It is anticipated that ALRN-6924 will arrest the cell cycle in normal cells that express wild-type p53, but not in cancer cells with a TP53 mutation. Thus, treatment should limit the off-target toxicity of DNA-damaging chemotherapies that target rapidly proliferating cells.23

One of the most exciting strategies for targeting cells that have TP53 mutations is reactivation of the mutant protein. The most widely investigated drugs are PRIMA-1 (p53 reactivation and induction of massive apoptosis) and its methylated derivative, eprenetapopt.

Both are prodrugs that are converted into an active metabolite, methylene quinuclidinone, which binds covalently to thiol groups in the core of the mutant p53 protein and causes it to undergo a conformational change, restoring wild-type activity.9,12

Eprenetapopt is more potent and has improved membrane permeability compared with PRIMA-1, and it has become the focus of ongoing clinical trials.2,12 It demonstrated anticancer activity and had a favorable safety profile in a range of preclinical cancer models, which led to the commencement of early-stage clinical testing.2,12 In a first-in-human study, eprenetapopt was reported to be safe and showed some activity in patients with hematologic malignancies (NCT00900614).24

Patients with TP53-mutant MDS have a particularly poor prognosis, and new treatment options are needed.25 In a phase 1/2 study (NCT03072043), eprenetapopt was evaluated in combination with the hypomethylating agent azacitidine in patients with TP53-mutant higher-risk MDS or oligoblastic ( 30% blasts) AML.26

Phase 1b results demonstrated that eprenetapopt treatment led to transcriptional activation of p53 target genes. Additionally, patients experienced predominantly grade 1 or 2 AEs, and there were no DLTs. Among 11 evaluable patients, there were 9 CRs and 2 bone marrow CRs.26

Results from the phase 2 portion of the trial were presented at the 2019 ASH meeting. A total of 49 patients had been enrolled and treated with the recommended phase 2 dose of 4500 mg administered intravenously on days 1 to 4 in combination with azacitidine 75 mg/m2 for 7 days (days 4-10 or days 4-5 and 8-12) in 28-day cycles. The median age of patients was 66 years, and most patients had MDS, all higher risk.

The ORR was 87%, including a 53% CR rate and 18% bone marrow CR with hematologic improvement. An additional 4 patients had SD, and just 2 had progressive disease. Median DOR was 6.5 months.

Having TP53 as the sole gene mutation was predictive of a higher CR rate (69% vs 25%; P = .006), and there was a nonsignificant trend toward higher ORR in these patients (93% vs 75%; P = .17). In the overall cohort, the median OS was 11.6 months. The 18 patients who discontinued study treatment to proceed to stem cell transplant had better median OS than those who did not (16.1 months vs 9.2 months). TRAEs included nausea, vomiting, dizziness, constipation, neuropathy, leukopenia, and thrombocytopenia.7

Based on these findings, the FDA granted fast track and orphan drug designations to eprenetapopt for MDS treatment.6 A phase 3 clinical trial of eprenetapopt in combination with azacitidine in patients with TP53mutated MDS is ongoing (NCT03745716),7 and Aprea Therapeutics recently reported that enrollment was complete, with topline results expected in late 2020.27

Interim results of a French trial were also presented at the 2019 ASH meeting. Fifty-three patients (34 with MDS and 19 with AML, all higher risk and harboring TP53 mutations) were treated with 4500 mg of eprenetapopt on days 1 to 4 and azacitidine 75 mg/m2 on days 4 to 10 of 28-day cyclesAmong 16 patients evaluable for response, The ORR was 75%, including 56% CR and 19% bone marrow CR or SD with hematologic improvement. Common TRAEs were febrile neutropenia and neurological toxicities, the latter including ataxia, cognitive impairment, acute confusion, isolated dizziness, and facial paresthesia.28

Eprenetapopt also demonstrated activity in combination with carboplatin and pegylated liposomal doxorubicin in patients with high-grade serous ovarian cancer, a cancer type with a high prevalence of TP53 mutations, in the phase 1/2 PiSARRO trial (NCT02098343).29

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Novel Strategies for Targeting the Guardian of the Genome Emerge - OncLive

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Industry Manufacture, Consumption, Export, Import by Regions (2014-2019) Industry Value ($) by Region (2014-2019)

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Major Region of COVID-19 Outbreak- CRISPR Marketi) Global COVID-19 Outbreak- CRISPR Salesii) Global COVID-19 Outbreak- CRISPR Revenue & market share Major Companies List Conclusion

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CRISPR Market to See Massive Growth by 2026 | GE Healthcare Dharmacon, CRISPR Therapeutics, Thermo Fisher Scientific - Aerospace Journal

Smiths 2005 stem cell law to be reauthorized by House

Rep. Chris Smith (R-NJ)statement submitted during debate in the House of Representatives

on the Stem Cell Therapeutic and Research ActSeptember 29, 2020

Margaret Hahnmy mother-in-lawpassed away on Friday and a Mass of Christian burial will be held today at St. Mary Church in South Amboy, New Jersey. She was 96 and was deeply loved and will be deeply missed.

MargaretPegwas a great womanwife, mother, grandmother, and great-grandmother. She selflessly devoted her life to public service including her amazing work as Sayreville Borough Clerk for twenty years. She had an incredible reputation for getting things done for the people. No matter who served as mayor or on Council, everyone knew she was the power.

My wife Marie and I will join family and friends today at her funeral and internment making it impossible for me to speak today during the debate on the reauthorization of a law I originally authored fifteen years agothe Stem Cell Therapeutic and Research Act of 2005and the Stem Cell Therapeutic and Research Act of 2015.

So, I submit these comments for the Congressional Record.

Madam Speaker, today the House of Representatives will vote to reauthorize the Stem Cell Therapeutic and Research Act.

This was an original idea of mine 20 years ago. Joined by 70 cosponsors, I introduced it in 2001 and again in 2003.

After five long years of hard work and numerous setbacks, my bill was finally enacted into law in 2005.

Beginning in 2001, Dr. Joanne Kurtzberg, who is President of the Cord Blood Association, helped draft my original law.Dr. Kurtzberg has said, Cord blood transplantation is now an established field with enormous potential. In the future, it may emerge as a source of cells for cellular therapies focused on tissue repair and regeneration.

The new law created a nationwide umbilical cord blood stem cell program, designed to collect, derive, type, and freeze cord blood units for transplantation into patients to mitigate and to even cure serious disease. Pursuant to the law, it also provided stem cells for research. The new cord blood program was combined in our 2005 law with an expanded bone marrow initiative, which was crafted over several years by our distinguished colleague, CongressmanBill Young.

I was the prime sponsor again when it was reauthorized in 2015.

Umbilical cord blood stem cells, obtained after the birth of a child, have proved highly efficacious in treating 70 diseases, including sickle-cell disease, lymphoma, and leukemia. And scientists are continuing to study and better understand the regenerative effects of cord blood cell therapies for other diseases and conditions. Bone marrow donations provide lifesaving transplants to treat diseases like blood cancer, sickle cell anemia, or inherited metabolic or immune system disorders.

The National Cord Blood Inventory (NCBI) provides funding to public cord blood banks participating in the program to allow them to expand the national inventory of cord blood units available for transplant. These units are then listed on the registry by the Be the Match Program. The funds appropriated thus far have led to an important increase in the overall number of high-quality cord blood units available through the national registry, including 150,000 NCBI units. Within the Be the Match registry, there are more than 783,000 NCBI units worldwide.

The Program registry allows patients and physicians to locate matching cord blood units, as well as adult donors for marrow and peripheral blood stem cells, when a family donor is not available. The Program is the worlds largest, most diverse donor registry, with more than 22 million volunteers and more than 300,000 public cord blood units. To date, the National Marrow Donor Program/Be The Match (NMDP), through its operation of the Program, has facilitated more than 100,000 transplants. More than 45,000 patients have receivedcord bloodtransplants, according Dr. Joanne Kurtzberg.

The reauthorization before us authorizes $23 million to be appropriated for fiscal year 2021 through fiscal year 2025. It also authorizes $30 million to be appropriated for fiscal years 2021 through 2025 for the bone marrow transplant program. This continues funding at the same levels authorized in the 2015 authorization bill.

Madam Speaker, each year nearly 4 million babies are born in America. In the past, virtually every placenta and umbilical cord was tossed as medical waste. Today, doctors have turned this medical waste into medical miracles.

Not only has God in His wisdom and goodness created a placenta and umbilical cord to nurture and protect the precious life of an unborn child, but now we know that another gift awaits us immediately after birth. Something very special is left behindcord blood that is teeming with lifesaving stem cells. Indeed, it remains one of the best kept secrets in America that umbilical cord blood stem cells and adult stem cells in general are curing people of a myriad of terrible conditions and diseasesover 70 diseases in adults as well as in children.

The legislation that is before us will enable even more patients to receive the treatments that they so desperately need.

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Smith's 2005 stem cell law to be reauthorized by House - InsiderNJ

Its already hard enough for blood cancer patients to find a match through the international bone marrow registry, which pairs patients with potential donors who have the right type of tissue. But if youre Black and Jewish?

For people with multiple ethnic backgrounds who need marrow or stem cell transplants, matching is even harder.

I remember the doctor saying something like if he was an Irish white boy from Ireland, he might have a better chance, Monika Clark said about her son, 24-year-old Jordan Jackson-Clark of Oakland.

Jackson-Clark, whom his mom describes as mixed ethnicity and biracial, is likely to need a bone marrow transplant after a diagnosis of leukemia two weeks ago.

It was so out of the blue, Clark said. It was so unexpected.

Jackson-Clark had experienced a few bouts of intense stomach pain over the past summer, one strong enough to send him to the ER. Clark was concerned, but she was never expecting the recent call that they got from the doctor.

Through tears, Clark described the blow of hearing the diagnosis for her son, a Berkeley High School grad who was a camp counselor at the East Bay JCC and a member of the Jewish fraternity AEPi.

Hes just a gentle, loving young man, she said.

Jackson-Clark has acute myeloid leukemia, a cancer of the blood and bone marrow. Hes in the hospital getting chemotherapy for the next few weeks. In the meantime, knowing how difficult it will be to find a match for her son, Clark is desperately trying to get the word out about the bone marrow registry.

Please step out and do something very simple to save a life, she said.

The ethnic background of a cancer patient who needs a transplant matters, because the markers used to match a donor and patient are inherited. Having the same markers as a donor makes it a lot more likely that the patients body will accept the life-saving bone marrow or stem cells.

But the makeup of the database of potential donors is mostly white. For people of color and mixed race, the percentage of matches is 23 percent, and for white Caucasians its 77 percent, Clark said.

According to the nonprofit Gift of Life, while more than 12 percent of the American population is Black, only 4 percent on the registry are, and the percentages are similarly out of proportion for other ethnic groups.

Gift of Life was founded by Jay Feinberg, who was diagnosed with leukemia more than 20 years ago and needed a bone marrow transplant from a white Ashkenazi Jew. He sought a donor match, but at that time the database was sorely lacking in diversity. Efforts since then by his organization and others have greatly increased ethnic representation in the registry, but matches for mixed-ethnicity patients remain scarce. Jackson-Clark has the best chance of being matched with another person who is Black, white and Ashkenazi, but there simply arent many in the database.

The solution is getting more potential donors into the system. Clark is asking people to get tested with a simple cheek swab through Be the Match or any other registration service not only if they think they might be a match for her son, but also for all of the other patients out there who need matches. Optimal donor ages are 18 to 44; registration is free and can be done through the mail. That puts them on the international registry of potential donors, and the more people who are on the list, the more likely it is that they could be a match for a cancer patient.

Thats why Rabbi Yigal Rosenberg of Chabad of Santa Clara held a registration drive in February and encouraged young people to get on the list. When he got a call from Gift of Life a few days later, he thought it had something to do with the event.

They said, actually, you are a match! he said.

Rosenberg had the right kind of stem cells to help a 40-year-old man based on a swab hed given 10 years previously in New Jersey. (Whether marrow or stem cells are donated depends on the patients treatment needs.)

Im like, what are the chances? Rosenberg said. Literally I just hosted an event two days ago!

He immediately said yes and began a required series of injections to boost stem-cell production checking with another rabbi to make sure it was OK to have the shots on Shabbat as well.

This is the one thing youre allowed to compromise on, in Shabbat observance, is to save a life, he said.

Then, at the beginning of September, he drove down to San Bernardino, where he was put up in a hotel. He spent one day at the donation center attached to a machine that pumped blood out, filtered out and collected the stem cells, and returned the blood to his body. Rosenberg said the experience wasnt difficult at all.

I just felt so empowered during the entire process, he said.

He even livestreamed it on Facebook as a way to encourage more registrations, and to dispel some of the fear around donation. (Whether a patient requires the donors marrow or stem cells depends on the particular treatment protocol.)

I went right back to the hotel, jumped in the Jacuzzi for a bit and took a nap, he said. The next day he was back on his way to Santa Clara to resume his duties.

Clark, a former JCC preschool teacher, said it is important for people to know that donating stem cells and even bone marrow is not as intrusive or painful as it used to be. And anyone on the registry can always decide later that theyre not ready to donate, so getting the swab does not commit them to doing so.

The greatest Rosh Hashanah gift from the Jewish and biracial communities would be to spread the word far and wide with your communities, and to please get on the donor list by sending away for a simple and free cheek swab, she said. You just might save my or someone elses childs life.

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Oakland 24-year-old seeking multiethnic bone marrow donor - The Jewish News of Northern California

A stunning, 99-million-year-old fossil has captured a hell ant in the act of attacking its prey.

It provides rare evidence for how these extinct insects hunted with their scythe-like mandibles and horn-like headgear.

The hell ant belongs to a previously identified species called Ceratomyrmex ellenbergeri. It was preserved in amber found in Myanmar (formerly Burma) along with its insect prey, an extinct relative of the cockroach.

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Like other species of hell ant, Ceratomyrmex sports a pair of deadly mandibles that snap upwards in a vertical motion, unlike the mandibles of modern ants, which move horizontally. Also unlike modern ants, the hell ants have horns protruding from their heads.

The new fossil provides direct evidence that hell ants, which are believed to have become extinct along with the dinosaurs some 65 million years ago, used their headgear to hunt, snapping their mandibles to pin their prey against the horn.

The hell ant, belonging to a species called Ceratomyrmex ellenbergeri, and its prey were found in Myanmar preserved in amber Current Biology/2020 Elsevier Inc/NJIT, Chinese Academy of Sciences and University of Rennes, France

To see an extinct predator caught in the act of capturing its prey is invaluable, said study leader Dr Phillip Barden at New Jersey Institute of Technology in the US.

This fossilised predation confirms our hypothesis for how hell ant mouthparts worked.

The only way for prey to be captured in such an arrangement is for the ant mouthparts to move up and downward in a direction unlike that of all living ants and nearly all insects.

Bardens team thinks that the early ancestors of hell ants would have first gained the ability to move their mouthparts vertically, while the diverse horns evolved later.

Some hell ant species had horns with serrated teeth, while one species is believed to have impaled its victims on a horn that was reinforced with metal.

The team now hopes to find more ancient ant fossils, with the aim of understanding why hell ants went extinct, while their modern-day equivalents thrived.

Asked by:Alec Maddocks, via email

To de-extinct an animal, you need a source of the animals DNA, which provides the blueprint for making it. DNA is sometimes preserved in fossils, and the oldest DNA extracted to date comes from a 700,000-year-old horse bone found in the Canadian permafrost.

However, DNA breaks down over time, and scientists think that its unlikely to be found in any specimen older than a million years. Dinosaurs went extinct 65 million years ago. No dinosaur DNA, no dinosaurs. Sorry!

Some other species, however, are fair game. In 2003, scientists briefly de-extincted a type of goat, called the bucardo. DNA-laden cells, taken from the last living female before she died, were used to create a clone, and the resulting embryo was transplanted into the womb of a living domestic goat.

The bucardo was delivered by Caesarean section, but died shortly after birth due to lung defects. The bucardo was therefore the first animal to be de-extincted, but also the first animal to go extinct twice!

Other de-extinction projects include attempts to revive an Australian amphibian called the gastric-brooding frog, a North American bird called the passenger pigeon and the one and only woolly mammoth. These use a combination of cloning, gene-editing and stem cell methods, but dont hold your breath waiting for the pitter-patter of tiny feet. De-extinction is still very much in its infancy, so for now, take solace in the fact that dinosaurs never really left us. Birds are their direct descendants, and theyre everywhere.

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99-million-year-old fight between hell ant and its prey preserved in amber - BBC Focus Magazine