Akari Therapeutics Reports Third Quarter 2020 Financial Results and Highlights Recent Clinical Progress – GlobeNewswire

December 11, 2020 09:00 ET | Source: Akari Therapeutics Plc

NEW YORK and LONDON, Dec. 11, 2020 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement (C5) and/or leukotriene (LTB4) systems are implicated, today announced financial results for the third quarter ended September 30, 2020, as well as recent clinical progress.

With the imminent opening of our Phase III trial in pediatric patients with HSCT-TMA in Europe and a clear regulatory path in the U.S. and Europe for our Phase III study in patients with BP, we are now in the exciting position of progressing two Phase III programs in orphan diseases in which there are no approved treatments, said Clive Richardson, Chief Executive Officer of Akari Therapeutics.

Third Quarter 2020 and Recent Clinical Highlights

Akaris two lead programs in BP and HSCT-TMA are in Phase III development. The Company also has programs addressing lung and ophthalmology diseases.

Phase III clinical trial in patients with BP

Phase III clinical trial in pediatric patients with HSCT-TMA

Ophthalmology program

Lung program

PNH - long term data

Third Quarter 2020 Financial Results

COVID-19 Corporate Update

Akaris clinical trial sites are based in areas currently affected by the global outbreak of the COVID-19 pandemic, and public health epidemics such as this can adversely impact the Companys business as a result of disruptions, such as travel bans, quarantines, and interruptions to access the trial sites and supply chains, which could result in material delays and complications with respect to research and development programs and clinical trials. Moreover, as a result of the pandemic, there is a general unease of conducting unnecessary activities in medical centers. As a consequence, the Companys ongoing trials have been halted or disrupted. For example, the Phase I/II clinical trial in patients with AKC study has been halted and recruitment in the Phase III clinical trial in pediatric patients with HSCT-TMA has been and may continue to be delayed. It is too early to assess the full impact of the coronavirus outbreak on trials for nomacopan, but coronavirus is expected to affect Akaris ability to complete recruitment in the original timeframes. The extent to which the COVID-19 pandemic impacts operations will depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the duration and continued severity of the outbreak, and the actions that may be required to contain the coronavirus or treat its impact. In particular, the continued spread of COVID-19 globally, could adversely impact the Companys operations and workforce, including research and clinical trials and the ability to raise capital, could affect the operations of key governmental agencies, such as the FDA, which may delay the development of the Companys product candidates and could result in the inability of suppliers to deliver components or raw materials on a timely basis or at all, each of which in turn could have an adverse impact on the Companys business, financial condition and results of operation.

About Akari Therapeutics

Akari is a biopharmaceutical company focused on developing inhibitors of acute and chronic inflammation, specifically for the treatment of rare and orphan diseases, in particular those where the complement (C5) or leukotriene (LTB4) systems, or both complement and leukotrienes together, play a primary role in disease progression. Akari's lead drug candidate, nomacopan (formerly known as Coversin), is a C5 complement inhibitor that also independently and specifically inhibits leukotriene B4 (LTB4) activity.

Cautionary Note Regarding Forward-Looking Statements

Certain statements in this press release constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. You should not place undue reliance upon the Companys forward looking statements. Except as required by law, the Company undertakes no obligation to revise or update any forward-looking statements in order to reflect any event or circumstance that may arise after the date of this press release. These forward-looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control. Such risks and uncertainties for our company include, but are not limited to: needs for additional capital to fund our operations, our ability to continue as a going concern; uncertainties of cash flows and inability to meet working capital needs; an inability or delay in obtaining required regulatory approvals for nomacopan and any other product candidates, which may result in unexpected cost expenditures; our ability to obtain orphan drug designation in additional indications; risks inherent in drug development in general; uncertainties in obtaining successful clinical results for nomacopan and any other product candidates and unexpected costs that may result therefrom; difficulties enrolling patients in our clinical trials; our ability to enter into collaborative, licensing, and other commercial relationships and on terms commercially reasonable to us; failure to realize any value of nomacopan and any other product candidates developed and being developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; inability to develop new product candidates and support existing product candidates; the approval by the FDA and EMA and any other similar foreign regulatory authorities of other competing or superior products brought to market; risks resulting from unforeseen side effects; risk that the market for nomacopan may not be as large as expected; risks associated with the impact of the COVID-19 pandemic; risks associated with theSECinvestigation; inability to obtain, maintain and enforce patents and other intellectual property rights or the unexpected costs associated with such enforcement or litigation; inability to obtain and maintain commercial manufacturing arrangements with third party manufacturers or establish commercial scale manufacturing capabilities; the inability to timely source adequate supply of our active pharmaceutical ingredients from third party manufacturers on whom the company depends; unexpected cost increases and pricing pressures and risks and other risk factors detailed in our public filings with theU.S. Securities and Exchange Commission, including our most recently filed Annual Report on Form 20-F filed with theSEC. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release and we undertake no obligation to update or revise any of these statements to reflect events or circumstances occurring after this press release. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release.

AKARI THERAPEUTICS, Plc

CONDENSED CONSOLIDATED BALANCE SHEETS As of September 30, 2020 and December 31, 2019 (in U.S. Dollars, except share data)

AKARI THERAPEUTICS, Plc

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS) - UNAUDITED For the Three and Nine Months Ended September 30, 2020 and September 30, 2019 (in U.S. Dollars)

For more information Investor Contact:

Peter Vozzo Westwicke (443) 213-0505 peter.vozzo@westwicke.com

Media Contact:

Sukaina Virji / Lizzie Seeley Consilium Strategic Communications +44 (0)20 3709 5700 Akari@consilium-comms.com

Link:
Akari Therapeutics Reports Third Quarter 2020 Financial Results and Highlights Recent Clinical Progress - GlobeNewswire

Researchers identify the origin of a deadly brain cancer – McGill Newsroom

Finding could lead to potential therapies

Researchers at McGill University are hopeful that the identification of the origin and a specific gene needed for tumour growth could lead to new therapeutics to treat a deadly brain cancer that arises in teens and young adults. The discovery relates to a subgroup of glioblastoma, a rare but aggressive form of cancer that typically proves fatal within three years of onset. The findings are published in the latest issue of the journalCell.

To complete their study, the research team, led by McGills Dr. Nada Jabado, Professor of Pediatrics and Human Genetics and Dr. Claudia Kleinman, Assistant Professor of Human Genetics, assembled the largest collection of samples for this subgroup of glioblastoma and discovered new cancer-causing mutations in a gene called PDGFRA, which drives cell division and growth when it is activated.

The researchers noted that close to half of the patients at diagnosis and the vast majority at tumour recurrence had mutations in this gene, which was also unusually highly expressed in this subgroup of glioblastoma. We investigated large public datasets of both children and adult patients in addition to those we had generated from patients samples in the lab and came to the same conclusion, PDGFRA was unduly activated in these tumours. This led us to suspect this kinase plays a major role in tumour formation explains Dr Carol Chen, a postdoctoral fellow, and Shriya Deshmukh an MD-PhD candidate in the Jabado lab and the studys co-first authors.

Employing a big data resource generated by their team using new technologies that measure the levels of every gene in thousands of individual cells, they were able to discover that this brain tumour originates in a specific type of neuronal stem cell. We used single cell analyses to create an atlas of the healthy developing brain, identifying hundreds of cell types and their traits, explains Selin Jessa, a PhD student in the Kleinman lab and co-first author on this study. Since these brain tumours retain a memory, or footprint, of the cell in which they originated, we could then pinpoint the most similar cell type for these tumours in the atlas, in this case, inhibitory neuronal progenitors that arise during fetal development or after birth in specific structures of the developing brain, adds Dr. Kleinman who leads a computational research lab at the Lady Davis Institute at the Jewish General Hospital.

An unexpected finding

The researchers note that the PDGFRA gene is not usually turned on in this neuronal stem cell population. By using sequencing technologies that measure how a cells DNA is spatially organized in 3D, notes Djihad Hadjadj, a postdoctoral fellow in the Jabado lab and the studys co-first author, We found that, exquisitely in this neuronal stem cell, the DNA has a unique structure in the 3D dimension that allows the PDGFRA gene to become activated where it shouldnt be, ultimately leading to cancer.

The finding is also important in properly classifying the tumour. Previously, this tumour type was classified as a glioma, because under the microscope, it resembles glial cells, one of the major cell types in the brain, says Dr. Jabado, who holds a CRC Tier 1 in Pediatric Oncology in addition to being a clinician scientist at the Montreal Childrens Hospital and leading a research lab focused on studying brain tumours at the Research Institute of the McGill University Health Centre. Our work reveals that this is a case of mistaken identity. These tumours actually arise in a neuronal cell, not a glial cell.

A hope for potential treatment

PDGFRA is targetable by drugs that inhibit its activity, and there are, in fact already approved drugs that target it for other cancers for which mutations in this gene are responsible, such as gastrointestinal stromal tumours. This offers hope for work into finding targeted therapies for this group of deadly brain tumours, note the researchers.

The combined studies of the genome, including at the single cell level and the genomic architecture in 3D of the tumour compared to the normal developing brain, were crucial in this study. They helped identify the specific timepoints during development where the cell is vulnerable to the cancer-driver event in these gliomas, which were revealed to be neuronal tumours. Importantly, the authors unravel genetic events that could lead to targeted therapy in a deadly cancer. Our findings provide hope for improved care in the near future for this tumour entity as these exquisite vulnerabilities may pinpoint to treatments that would preferentially attack the bad cells, say Drs. Jabado and Kleinman, who have joined efforts in the fight against deadly brain tumour. Stalled development is at the root of many of these cancers. The same strategy will prove important to unravel the origin, identify and exploit specific vulnerabilities, and orient future strategies for earlier detection in other brain tumour entities affecting children and young adults.

This study was made possible in large part thanks to support from the Genome Canada LSARP project Tackling Childhood Brain Cancer at the root to improve survival and quality of life, which includes funding from Genome Canada, Genome Quebec, CIHR and other sources, as well as the Fondation Charles-Bruneau and the National Institutes of Health.

Histone H3.3G34-Mutant Interneuron Progenitors Co-optPDGFRAfor Gliomagenesis, by C. Chen, S. Deshmukh, S. Jessa, D. Hadjadj, C. Kleinman, N. Jabado, et al, was published in the journalCellon December 10, 2020. DOI:https://doi.org/10.1016/j.cell.2020.11.012

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Researchers identify the origin of a deadly brain cancer - McGill Newsroom

Insights on the Global Stem Cell Therapy Market 2020-2024: COVID-19 Analysis, Drivers, Restraints, Opportunities, and Threats – Technavio – Yahoo…

Bloomberg

(Bloomberg) -- Guy Fieris Times Square restaurant, where Jared Kushner and Ivanka Trump partied in late 2016 before heading to Washington, is gone. The office tower at 666 Fifth Ave., once the headquarters of the Kushner familys real estate empire, has been sold. So too has a stake in a project in the trendy Dumbo neighborhood of Brooklyn.New York looks a lot different now than it did before Jared Kushner left town to take a job as a senior adviser to his father-in-law, President Donald Trump. Kushner Cos., the company where he was chief executive officer, has pulled back from the city, winnowing almost a decades worth of investments in a few years. Instead, it has relocated its ambitions to apartment complexes in New Jersey and Florida.It isnt clear if Kushner will return to an active role in the company after four years in the White House, or even if hell go back to New York. The changes made in his absence by his father Charles Kushner and company president Laurent Morali come after a decade-long push into the city, most of it when Jared Kushner was CEO. Although there were successes, some of the biggest deals foundered. High purchase prices, excessive borrowing and unrealistic expectations were followed by declining valuations and debt renegotiations.Kushner Cos. didnt respond to questions about whether Jared Kushner would rejoin the company or about the change in strategy. But Christopher Smith, its top lawyer, pointed in an email to a number of profitable transactions, including investments in Lower Manhattan and the Gowanus neighborhood of Brooklyn. He said other buildings had gained in value.During the Trump years Kushner Cos. chased investors from China, Qatar and Israel as Jared Kushner was helping shape foreign policy. He stepped down from his role at the company and transferred some of his assets to family members, but the structure of the divestments wasnt clear, exacerbating ethics concerns.At the same time, the company purchased apartment buildings in the suburbs of New Jersey, Maryland and Virginia, markets that are now booming as people flee cities during the Covid-19 pandemic. It is also looking to break into new territory: multifamily projects in South Florida.Some of the transactions that brought the company to this point have been painful. The 2018 sale of 666 Fifth Ave. was necessary to pay off a loan incurred in 2007, at the peak of the market, when Kushner Cos. purchased the office tower for a then-record $1.8 billion. Jared Kushner didnt become CEO until the following year, but he was involved in the negotiations and touted the purchase in a news release as having great upside potential.Saying goodbye to the property a 99-year lease on the office space was sold to Brookfield Asset Management Inc. for $1.3 billion was a comedown from plans to demolish the building and replace it with an even taller skyscraper in partnership with Chinas Anbang Insurance Group, an option weighed by the company during Kushners first months in the White House.A few blocks away theres the Times Square retail property six floors of the building that once housed the New York Times. Kushner Cos. bought the space in 2015, and a year later raised $370 million of debt based on an appraisal price of $470 million, a 59% increase over what it had paid.Now it looks as though the financial assumptions underpinning that valuation were a mirage. To fill the building, Kushner Cos. turned to tenants whose need for space was great but whose assessment of demand for experiential attractions turned out to be misguided. There was an exhibit featuring digital dolphins, and another with detailed miniatures of world monuments.By the end of last year, Guys American Kitchen & Bar was closed, a planned food hall never opened, a third tenant went bankrupt and a fourth wasnt paying full rent. Kushner Cos. defaulted on $85 million of its debt there last December, and an August appraisal put the propertys value at $92.5 million, lender records show, about a 70% drop from the purchase price.The former New York Times building was really a retail disaster, said Joshua Stein, a New York-based real estate attorney. One concept after another failed.Kushner Cos. also sold a less than 5% stake in the Watchtower complex in Brooklyns Dumbo neighborhood, acquired from the Jehovahs Witnesses in 2016. Jared Kushner, whose father-in-law was running for president at the time, trumpeted plans to convert the buildings into stores and loft office spaces. Kushners father decided to refocus elsewhere.The list of New York sales since January 2017 includes two other Brooklyn development sites and apartments in Queens. The company hasnt announced any major acquisitions in the city since then.Some New York deals that originated during Jared Kushners tenure have been successful. Three properties were sold for a combined gross profit of $239 million, according to data provided by Smith, the companys lawyer. But thats more than offset by about $200 million in operating losses at 666 Fifth Ave. after debt payments, figures provided by lenders to investors show, and a $200 million drop in value for the Times Square space.New York isnt the only big city where Kushner Cos. is retrenching. The company has been in talks to offload its only Chicago office property, a 31-story tower originally built for AT&T Inc., for $188 million, a 32% discount from the 2007 purchase price and barely enough to cover the propertys mortgage.Investments in other markets have been ample. In 2019, the company made its biggest purchase in more than a decade, spending more than $1 billion on 6,000 apartments in the Baltimore and Washington suburbs. Two years earlier, it had teamed up with Israels largest asset manager to purchase 1,000 apartments in Plainsboro, New Jersey.The companys return to its suburban roots might seem a surprising denouement, at least to those who thought Jared Kushners public role might facilitate private deal-making. But working for Trump often proved more awkward than lucrative.Kushners rising star attracted interest from investors who hadnt done business with his familys company. It also drew public scrutiny when his sister, Nicole Kushner Meyer, mentioned her brothers White House role while pitching investors in China on a project in Jersey City, New Jersey. The company later apologized to anyone who interpreted her remarks as an attempt to lure investors.Anbang, which made real estate purchases across the U.S. prior to Trumps China-bashing ascent to the White House, walked away from 666 Fifth Ave. soon after Bloomberg News reported details of a proposed deal with Kushner Cos. in early 2017 that would have provided a $4 billion construction loan and a $400 million payout to the Kushners. Chinese authorities seized Anbang the following year and imprisoned its chairman on unrelated fraud and embezzlement charges.Qatari royals also weighed an investment in 666 Fifth Ave. During the 2016 presidential campaign, Jared Kushner and his father had talked with Sheikh Hamad bin Jassim Al Thani, whod previously served as Qatars prime minister and head of its sovereign-wealth fund, about investing in the tower. The deal would have included $500 million from the sheikhs investment firm, contingent on finding other investors. Talks stalled after simultaneous negotiations with Anbang fell apart.One Kushner Cos. business partner who asked not to be identified discussing the closely held business said Jared Kushners work as Trumps emissary to Israel and the Middle East introduced him to a new set of wealthy investors who could become partners once he returns to the private sector.Last week, on what may be his last trip to the region, Jared Kushner worked to bridge the divide between Saudi Arabia and Qatar, which had worsened after Saudi Arabia launched a blockade of its neighbor that Trump backed. A spokesman for the White House declined to comment.The company also is positioned to benefit from Trumps 2017 tax law, which created incentives to invest in low-income neighborhoods designated as opportunity zones. One Florida development is in such an area, which allows investors to defer taxes on capital gains reinvested there. Kushner Cos. is expanding properties in zones in the New Jersey beach town of Long Branch. It has declined to say whether its taking advantage of the tax breaks, and no public disclosures are required.Whether he does come back to the family real estate business, Jared Kushner still owns a stake in Cadre, the startup he cofounded that sells fractional shares of investments in property deals. Cadre arranged to buy him out last year, but the deal was shelved after the pandemic hit, and the company has reduced staff and made other cutbacks. A spokesman for Cadre didnt provide comment.For more articles like this, please visit us at bloomberg.comSubscribe now to stay ahead with the most trusted business news source.2020 Bloomberg L.P.

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Insights on the Global Stem Cell Therapy Market 2020-2024: COVID-19 Analysis, Drivers, Restraints, Opportunities, and Threats - Technavio - Yahoo...

Better education needed to give patients improved understanding of gene therapies, new review highlights – University of Birmingham

Skip to main content Older, male patients with more severe underlying conditions and a greater risk of death tended to be more accepting of new approaches such as stem cell research

A new review of research bringing together patient, carer and public views of cell and gene therapies has highlighted a need for appropriate education to better inform people including how clinical trials work and the risks and benefits of various treatments.

Over the last decade, new cell, gene and tissue-engineered therapies have been developed to treat various cancers, inherited diseases and some chronic conditions. They offer opportunities for the treatment of disease and injury, to restore function, and in some cases offer cures. In response the NHS Advanced Therapies Treatment Centres (ATTCs) were set up to bring together the health service, academia and industry to address the unique and complex challenges of bringing these therapies to patients.

Led by experts from the Centre for Patient Reported Outcome Research (CPROR) at the University of Birmingham and the Midlands and Wales ATTC (MW-ATTC), the review, funded by a MW-ATTC grant from UK Research and Innovation is the first of its kind and the first to consider both patient and public opinions of cell and gene therapies. Examining 35 studies, the majority of which were published between 2015 and 2020, analysis showed that a lack of understanding of the aims of clinical trials and overestimation of the potential benefits of cell and gene therapy were common among both patients and the general public. Patients were generally of the opinion that more information about participating in clinical trials is vital to enable them to make informed assessment of potential risks and benefits.

Older, male patients with more severe underlying conditions and a greater risk of death tended to be more accepting of new approaches such as stem cell research and generally, while views of therapies varied among patients, the provision of adequate information increased acceptance.

Interestingly the review also found that patients considered their clinicians to be the most trustworthy source of information which would suggest that patients would approach and discuss these treatments with their physicians. However, researchers found that this might not always be the case due to a number of reasons including the perception that clinicians do not always approve of cell and gene therapies and may try to discourage them from pursuing treatment and may not have enough knowledge of the field to provide adequate advice.

Lead author Dr Olalekan Lee Aiyegbusi, Co-Deputy Director of the Centre for Patient Reported Outcomes Research (CPROR) said: The findings from this research are intended to inform the patient engagement work of the ATTCs. We hope that by highlighting various issues, efforts will be made to correct misconceptions, and improve the awareness of patients and the public about the potential benefits and risks associated with cell and gene therapies.

It is important that the public and patients are aware of these therapies, understand the issues involved, and can contribute to the ongoing debates. A high level of awareness will also enhance patients ability to make informed decisions about participating in clinical trials and routine administration of cell and gene therapies.

The full paper Patient and public perspectives on cell and gene therapies: a systematic review was published today (Tuesday 8 December 2020) in Nature Communications.

ENDS

For more information please contact Sophie Belcher, Communications Manager, University of Birmingham, on +44 7815607157. Alternatively, contact the Press Office out of hours on +44 (0)7789 921165.

DOI: 10.1038/s41467-020-20096-1.Full paper: http://www.nature.com/ncomms

The University of Birmingham is ranked amongst the worlds top 100 institutions, and its work brings people from across the world to Birmingham, including researchers and teachers and more than 6,500 international students from nearly 150 countries.

About the Midlands and Wales ATTC (MW-ATTC)

The 9M Midlands and Wales Advanced Therapy Treatment Centre (MW-ATTC) is one of three national Innovate UK funded centres whose goal is to accelerate the delivery of advanced therapies.

It is a regional network spanning the Midlands & Wales comprising a large consortium of industry, healthcare and university partners with expertise in advanced therapy manufacturing including academic and commercial partners, logistics companies, specialists in clinical trial delivery and teams focussed on IT logistics solutions and health economics.

The aim of the MW-ATTC is to enable UK advanced therapy companies to reach the clinical market, whilst simultaneously building clinical capacity regionally to deliver these breakthrough therapies to patients.

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Better education needed to give patients improved understanding of gene therapies, new review highlights - University of Birmingham

Extended Virus Shedding After COVID in Some Patients With Cancer – Medscape

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset, and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma.

The finding was reported December 1 in a research letter in the New England Journal of Medicine.

Individuals who are otherwise healthy when they get COVID-19 are "no longer infectious after the first week of illness," commented lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York City.

"We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others," she added.

Kamboj told Medscape Medical News that her team's previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than healthy controls.

Based on their latest findings, investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, "it's a residual risk that we need to address," Kamboj said.

Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).

Of these 20 patients, 15 were receiving active treatment or chemotherapy. Eleven out of the group developed severe COVID-19 infection.

In total, 78 respiratory samples were collected. "Viral RNA was detected for up to 78 days after the onset of symptoms," researchers report, "[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing."

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of 5 patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. Interestingly, this patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes, and found that "each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates." These findings were consistent with persistent infection, they note.

The authors have disclosed no relevant financial relationships.

N Engl J Med. Published online December 1, 2020. Research letter

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Extended Virus Shedding After COVID in Some Patients With Cancer - Medscape

Global Cancer Stem Cells Market to Boost with CAGR of 11.8% and Cross a Margin of $1,898.3 Million During the Covid-19 Outbreak Exclusive Report [150…

December 08, 2020 09:05 ET | Source: Research Dive

New York, USA, Dec. 08, 2020 (GLOBE NEWSWIRE) -- The cancer stem cells market is anticipated to grow rapidly in the Covid-19 outbreak due to usage of cancer stem cells for treating cancer. According to a report published by Research Dive, the cancer stem cells market is expected to cross a margin of $1,898.3 million, from a market size of $786.3 million in the year 2018, with significant CAGR of 11.8% during 2019-2026.

This report consists of in-depth viewpoints of the effects of COVID-19 crises on the future and current evolution of the industry worldwide. This is carried out by analyzing significant facets such as limitations, drivers, newest trends, size and scope, advances, and the position of the regional markets during the pandemic phase. The report also mentions that the COVID-19 pandemic has positively impacted the market conditions.

For More Detail Insights, Download Sample Copy of the Report at: https://www.researchdive.com/download-sample/203

Aspects Affecting the CAGR Figures in Pre and Post Covid-19 Situation

Market forecasts before the Covid-19 outbreak suggest that CAGR stood at 10.3% and according to 2020 estimates the market is predicted to reach CAGR of 11.8%.

The growth in the market is due to the utilization of cancer stem cells for treating cancer that is diagnosed in metastatic stage. Moreover, rise in morbidity and mortality rate is also driving the market forward.

Factors Affecting the Revenue in Pre and Post Covid-19 Period

The cancer stem cells market is predicted to garner a revenue of $982.5 million in 2020, from an estimated market size of $956.6 million as anticipated before the Covid-19 outbreak.

Investments by government authorities for cell-based research are considered to propel the market growth. In addition, increase in R&D and personalized medication for treating various types of cancers by utilizing cell-based therapies will enhance the market growth. All these factors are responsible for the growth of the market.

Future Scope of the Market

This market will grow due to heavy investments in research and development fields that focus mainly on therapeutic effects on stem cells for stem cell banking and disease treatment. Moreover, PSC (pluri-potent stem cells) development for generating different germ cell layers is also projected to propel the market growth. The cancer stem cells market will rise significantly in the future due to the above stated reasons.

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Connect with Our Analyst to Reveal Anniversary Offers in detail: https://www.researchdive.com/connect-to-analyst/203

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Global Cancer Stem Cells Market to Boost with CAGR of 11.8% and Cross a Margin of $1,898.3 Million During the Covid-19 Outbreak Exclusive Report [150...

City of Hope Doctors Present Innovative Therapies to Better Treat Blood Cancers at American Society of Hematology Virtual Conference – BioSpace

Dec. 8, 2020 16:00 UTC

DUARTE, Calif.--(BUSINESS WIRE)-- City of Hope doctors participated in research presented at the American Society of Hematology (ASH) virtual meeting, Dec. 5 to 8, that are helping advance the treatment of blood cancers, including one study which demonstrated allogeneic stem cell transplants do have a survival benefit for older adults with myelodysplastic syndromes (MDS) compared with current standard of care.

The study is the largest and most definitive trial to demonstrate the benefits of an allogeneic stem cell transplantation for older adults with MDS, and is just one of numerous studies that City of Hope doctors help lead with the aim of finding more effective treatments of various blood cancers.

This years ASH conference truly showcases City of Hopes leadership in finding more effective treatments for blood cancers, said Stephen J. Forman, M.D., director of City of Hopes Hematologic Malignancies Research Institute. Whether its finding innovative treatments to make it possible for more older adults with cancer to receive stem cell transplants, or pursuing therapies that are more effective with fewer side effects, City of Hope doctors continue to lead innovative research in blood cancers and other hematological malignancies.

City of Hope doctors are leading novel clinical trials for patients with leukemia, lymphoma and other blood cancers.

Multicenter clinical trial led by City of Hope makes stem cell transplant possible for older adults with myelodysplastic syndromes

Allogeneic hematopoietic cell transplantation, or stem cell/bone marrow transplants, for blood cancers that have recurred or are difficult to treat can put the disease into long-term remission and provide a potential cure. The therapy establishes a new, disease-free blood and immune system by transplanting healthy blood stem cells from a donor into a cancer patient after destroying the patients unhealthy bone marrow.

City of Hope and other institutions started this therapy in 1976, primarily for younger patients with blood cancers. The therapy involves using high-dose chemotherapy and/or radiotherapy to make room for a person to receive new stem cells; serious side effects can also occur after transplant. Because of these and other considerations, for many years, older adults with blood cancers have not been considered for transplants.

City of Hope has been leading the way to make transplants possible for more older adults with various cancers.

A new study presented at ASH demonstrates transplants are now a possibility and beneficial for patients with myelodysplastic syndromes (MDS). Approximately 13,000 people in the United States each year are diagnosed with MDS, an umbrella term describing several blood disorders that begin in the bone marrow.

Co-led by City of Hopes Ryotaro Nakamura, M.D., director of City of Hopes Center for Stem Cell Transplantation, the study is the largest and first trial to demonstrate the benefits of an allogeneic stem cell transplantation for older adults with MDS as opposed to the standard of care currently provided to these patients. The multicenter trial for patients aged 50 to 75 with serious MDS compared how long transplant patients survived with those who didnt receive a transplant, as well as disease progression and quality of life. The transplant therapy used reduced-intensity conditioning, which delivers less chemotherapy and radiation before transplant and relies more on the anti-tumor effects of the therapy.

Between 2014 and 2018, the study enrolled 384 participants at 34 cancer centers nationwide. It included 260 patients who were able to find a donor for a transplant, as well as 124 patients who did not find a donor for a transplant.

After three years, nearly 48% of MDS patients who found a donor for transplant had survived compared with about 27% of those patients who didnt have a donor for transplant and received current hypomethylating therapy, a type of chemotherapy that is current standard of care for MDS. Leukemia-free survival which is relevant because myelodysplastic syndrome can develop into leukemia was also greater in transplant recipients after three years nearly 36% compared with about 21% for those who did not have a transplant.

There was a large and significant improvement in survival for patients who had a transplant, Nakamura said. The benefit margin in overall survival was over 20% (21.3%) for patients who had a transplant.

In addition, quality of life was the same for both transplant and nontransplant patients. There were no clinically significant differences when taking such measurements as physical and mental competency scores.

This is an extremely exciting study because it provides evidence that stem cell transplant is highly beneficial for older patients with serious MDS and will likely be practice-changing for this group, Nakamura said. Before, many doctors wouldnt even consider a transplant for this group of patients, but our study demonstrates that these patients should be evaluated for a transplant, which could potentially provide a cure for their disease.

The trial is part of Blood and Marrow Transplant Clinical Trials Network, which was established with support from the National Heart, Lung, and Blood Institute and National Cancer Institute, because of a critical need for multi-institutional clinical trials focused directly on improving survival for patients undergoing hematopoietic cell transplantation.

Updated results from a study of a potential new CAR T cell therapy, liso-cel, for relapsed/refractory chronic lymphocytic leukemia

Patients with relapsed or difficult-to-treat chronic lymphocytic leukemia/small lymphocytic leukemia continue to do well 24 months after receiving lisocabtagene maraleucel (liso-cel) chimeric antigen receptor (CAR) T cells, according to Tanya Siddiqi, M.D., director of City of Hopes Chronic Lymphocytic Leukemia (CLL) Program, which is part of the Toni Stephenson Lymphoma Center. She presented these findings during the 2020 ASH annual meeting virtual conference.

Overall, 23 and 22 patients were evaluated for safety and efficacy in this phase 1 trial, respectively. Their median age was 66 and they had received a median of four prior therapies; all patients had received prior ibrutinib, which is one of the standard of care drugs for CLL.

The overall response rate, or patients whose CLL diminished after liso-cel CAR T cell therapy, was 82%, and 45% of patients also had complete responses, or remissions.

After 15 months of treatment, 53% of patients maintained their responses to the therapy, and six patients continued to be in remission. After 18 months, 50% of patients maintained their response, and there were five remissions. All seven patients who completed the 24-month study maintained their response. Median progression-free survival, or the amount of time the cancer did not worsen during and after treatment, was 18 months.

As early as 30 days after receiving liso-cel, about 75% of 20 patients evaluated for the therapys efficacy had undetectable minimal residual disease (MRD, or no detectable traces of cancer) in the blood and 65% had undetectable MRD in the marrow.

These are remarkable results for a group of patients that prior to this CAR T treatment had no good treatment options if they had already progressed on novel targeted therapies like ibrutinib and venetoclax, Siddiqi said. Liso-cel is providing new hope for CLL patients, and the remissions are also long lasting with few serious side effects.

Because of its safety and effectiveness in clinical trials, liso-cel, which targets the CD19 protein on cancer cells, may soon receive approval from the Food and Drug Administration as a commercial therapy for relapsed or refractory B cell lymphoma. City of Hope is also taking part in the phase 2 trial of liso-cel in CLL patients.

Consolidation treatment with brentuximab vedotin/nivolumab after auto stem cell transplant for relapsed/refractory Hodgkin lymphoma patients leads to 18-month progression free-survival

Patients who have Hodgkin lymphoma that has not been cured by initial treatment will usually receive more chemotherapy and an autologous hematopoietic cell transplant. But even after a stem cell transplant, recurrence of the lymphoma is possible.

This multicenter phase 2 clinical trial, led by City of Hope, examined whether treating patients with brentuximab vedotin (BV), an antibody-based treatment that targets delivery of chemotherapy only to Hodgkin lymphoma cells, and nivolumab, which works by blocking the PD-1 immune checkpoint pathway that Hodgkin lymphoma hijacks to evade the immune system, was safe and effective as consolidation to prevent disease recurrence after transplant in patients with high-risk Hodgkin lymphoma.

Alex Herrera, M.D., assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, discussed 19-month progression-free survival for trial participants, as well as overall survival, safety and response rates during ASH.

Fifty-nine patients were enrolled in the trial. Patients received the consolidation treatment starting a median of 54 days after transplant, and received a median of eight cycles of the therapy. The 19-month progression-free survival in patients was 92%, and overall survival in patients was 98%. Only three patients relapsed after receiving BV and nivolumab consolidation after transplant, and one patient passed away due to PCP pneumonia unrelated to the study treatment.

The most common sides effects related to the treatment were peripheral neuropathy (51%), neutropenia (42%), fatigue (37%) and diarrhea (29%).

Using brentuximab vedotin and nivolumab after transplant is a promising approach for preventing relapse of Hodgkin lymphoma after transplant that merits further study, Herrera said.

City of Hope doctors published research on innovative approaches against graft-versus-host-disease

Historically, a bone marrow/stem cell transplant is more likely to be effective if patients have a donor who is a 100% match, or as close to that as possible. Finding that perfect match is more difficult for African Americans, Latinos, Asian Americans and other ethnic groups as bone marrow donor registries are still trying to increase the number of non-white donors.

Transplant doctors are also looking for ways to make the transplant more effective if a perfect match cant be found; donors who are not a 100% or close match are referred to as mismatched unrelated. One major barrier to these transplants being effective is a condition known as graft-versus-host-disease (GVHD). The condition, which is more common in transplants involving mismatched donors, is caused by donated cells that recognize the recipient's cells as foreign and attack them, damaging the skin, eyes, lungs, liver and digestive tract.

In order to help prevent GVHD, therapies can be given to patients after transplant. A prospective clinical trial at City of Hope examined whether using cyclophosphamide after an infusion of stem cells could prevent GVHD.

Thirty-eight patients were enrolled in the trial, which is the first to examine the use of cyclophosphamide in transplants with a mismatched unrelated donor.

With a median follow-up period of 18 months, 87% of patients had survived, and the majority did not relapse or develop severe GVHD.

During the first 100 days post-transplant, acute GVHD incidence was around 50%; most cases were mild to moderate while severe GVHD was only 15%. A year after transplant, 52% of patients had some form of chronic GVHD, but only 3% had moderate or severe chronic GVHD.

The trial also examined toxicities, infections and immune system recovery after the transplant.

Our study showed that patients who received a transplant from a mismatched unrelated donor using post-transplant cyclophosphamide had a comparable outcome to what we see in matched donor transplants with few cases of serious GVHD cases, said Monzr Al Malki, M.D., associate clinical professor of City of Hopes Department of Hematology & Hematopoietic Cell Transplantation and director of unrelated donor BMT and haploidentical transplant programs. Our data support further development of this therapy in transplant patients who would otherwise have no suitable donors and limited treatment options.

City of Hopes Anthony Stein, M.D., also led a pilot trial that examined whether a new treatment approach may reduce the rate of GVHD in patients with acute myelogenous leukemia (AML) who have received an allogeneic hematopoietic cell transplant. Although a transplant can put AML into remission, GVHD remains the main serious complication after transplant, impacting a patients quality of life and increasing health care costs.

Eighteen patients between the ages of 18 and 60 enrolled in the trial. Each patient received a novel conditioning regimen of total marrow and lymphoid irradiation, which targets a patients marrow and lymph nodes while reducing radiation to other parts of the body, and cyclophosphamide, a therapy that suppresses the immune system. Tacrolimus was also provided to patients.

Radiation was delivered twice daily on the fourth day before transplant and on the day of transplant without chemotherapy. Cyclophosphamide was given to patients on the third and fourth day after transplant.

There were mild to moderate toxicities. Acute GVHD developed in two patients and only one patient developed the most serious GVHD. Five patients developed mild chronic GVHD. Nearly 60% of patients had not developed GVHD or the condition had not worsened after a year.

After a year, all patients had survived, and 83% had not relapsed. After two years, nearly 86% of patients had survived, and the relapse number remained the same.

The therapeutic approach did not interfere with the transplant process as all patients engrafted, or the donors cells started to produce bone marrow and immune cells.

This is welcome news for AML patients who receive an allogeneic transplant and are concerned about developing GVHD, said Stein, associate director of City of Hope's Gehr Family Center for Leukemia Research. Our study demonstrated that using this new combination of therapies is safe and feasible and does not interfere with the engraftment process.

In addition, after a year, patients in this trial were no longer taking immunosuppressive therapy and had an improved quality of life, Stein said. He added that because many of the patients didnt have GVHD, health care costs after a year were also lower than if patients required treatment for the condition.

City of Hope now plans to start a larger phase 2 trial using this treatment approach.

Bispecific antibodies continue to show promise against blood cancers

Mosunetuzumab is a promising new immunotherapy for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL) that recently received breakthrough therapy designation from the Food and Drug Administration. The designation is intended to expedite the development and review of drugs for serious or life-threatening diseases.

Elizabeth Budde, M.D., Ph.D., assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, is leading clinical trials that are showing how well mosunetuzumab works against NHL. At this years ASH, one trial discussed is how the therapy is working for patients with follicular lymphoma.

Mosunetuzumab is a bispecific antibody targeting both CD3 (a protein found on the surface on T cells) and CD20 on the surface of B cells. The therapy redirects T cells to engage and eliminate malignant B cells.

Sixty-two patients, ranging in age from 27 to 85 years old, were enrolled in the trial for follicular lymphoma. They received intravenous doses of mosunetuzumab.

Sixty-eight percent of the patients responded to the therapy, and 50% had a complete response, or went into remission. Consistent complete response rates occurred even in patients with double refractory disease and patients who received prior CAR T cell therapy. Median duration of response was approximately 20 months, and media progression free survival was nearly one year.

Side effects were reported in 60 patients with serious adverse effects in 22 patients. The most frequently reported serious side effects were hypophosphatemia, an electrolyte disorder, and neutropenia, a condition caused by low numbers of white blood cells. Fourteen patients experienced cytokine release syndrome, but none required extensive treatment for it.

Neurological side effects included headache, insomnia and dizziness.

Patients in this trial had high response rates and their disease remained in control for a year, Budde said. This is remarkable because many patients were no longer responding to other therapies.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nations Best Hospitals in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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City of Hope Doctors Present Innovative Therapies to Better Treat Blood Cancers at American Society of Hematology Virtual Conference - BioSpace

New DARZALEX (daratumumab) Data from GRIFFIN Study Show Deeper and Longer Responses in Patients with Newly Diagnosed Multiple Myeloma – PRNewswire

HORSHAM, Pa., Dec. 7, 2020 /PRNewswire/ --The Janssen Pharmaceutical Companies of Johnson & Johnson announced new data from the randomized Phase 2 GRIFFIN study showing that the addition of DARZALEX (daratumumab) to lenalidomide (Revlimid), bortezomib (VELCADE) and dexamethasone (D-RVd), followed by DARZALEXplus lenalidomide (D-R) maintenance therapy, resulted in deeper and improved responses, including minimal residual disease (MRD) negativity, compared to RVd followed by R alone in newly diagnosed, stem cell transplant-eligible patients with multiple myeloma.1These data investigating the use of DARZALEX in combination with RVd, which were shared in separate oral and poster presentations at the American Society of Hematology (ASH) 2020 Annual Meeting, provide further evidence that this regimen may provide greater efficacy for transplant-eligible, newly diagnosed multiple myeloma(NDMM) than standard therapy. The oral presentation (Abstract #549) shared longer-term follow-up data, and the poster presentation (Abstract #3243) featured additional data from the safety run-in cohort.1,2

"The long-term GRIFFIN data show that maintenance therapy with DARZALEX in combination with lenalidomide (D-R) resulted in deeper responses compared to R alone in patients with multiple myeloma who are newly diagnosed and transplant-eligible," said Peter Voorhees, M.D., Atrium Health's Levine Cancer Institute and GRIFFIN study investigator. "These data indicate that the addition of DARZALEX to RVd followed by R maintenance results in improved response rates and depth of response during induction, consolidation and maintenance treatment cycles."

Key Findings from GRIFFIN (Abstract #549):The GRIFFIN oral presentation featured updated safety and efficacy data based onlonger follow-up for D-RVd and evaluated the potential role of D-R for maintenance therapy in patients with NDMM.1

Key Findings from GRIFFIN (Abstract #3243):The poster presentation shared final results of the safety run-in cohort (n=16 patients) from the GRIFFIN study. Theseadditional data showed that maintenance therapy with DARZALEX and lenalidomide (D-R) improved both the sCR rate and MRD negativity rate in patients with NDMMwho underwent D-RVd induction, autologous stem cell transplant (ASCT) and D-RVd consolidation. This deepening of responses was associated with durable remissions, and no new safety signals were observed with maintenance therapy.2

"We continue to be encouraged by the GRIFFIN data showing deeper and improved responses in patients with newly diagnosed, ASCT-eligible multiple myeloma," said Andree Amelsberg, M.D., MBA, Vice President, Oncology Medical Affairs, Janssen Scientific Affairs, LLC. "These data show promising results for patients with newly diagnosed multiple myeloma, and we remain committed to exploring the full potential of DARZALEX and DARZALEX FASPRO."

About the GRIFFIN Study4The Phase 2 GRIFFIN (NCT02874742) study has enrolled and treated more than 200 adults ages 18-70 years with NDMM and who are eligible for high-dose therapy/ASCT.

In the safety run-in cohort, patients received 25 mg of lenalidomide orally on Days 1-14; 1.3 mg/m2 of bortezomib subcutaneously on Days 1, 4, 8 and 11; and 20 mg of dexamethasone on Days 1, 2, 8, 9, 15 and 16, every 21 days during the induction and consolidation phases (Cycles 1-6). DARZALEX 16 mg/kg IV was given on Days 1, 8 and 15 of Cycles 1-4 and on Day 1 of Cycles 5-6.

During maintenance phase (Cycles 7-32), patients received 10 mg daily of lenalidomide (15 mg beginning at Cycle 10 if tolerated) on Days 1-21 every 28 days and DARZALEX 16 mg/kg IV every 56 days; this was amended to every 28 days based upon emerging clinical pharmacokinetic data demonstrating improved target saturation with every-4-week maintenance dosing. Maintenance therapy with lenalidomide may be continued beyond Cycle 32 in both arms, per local standard of care.

In the subsequent randomized Phase 2 portion of the study, approximately 200 patients were randomized and received treatment with RVd, induction and consolidation, ASCT and maintenance therapy with lenalidomide; or DARZALEX and RVd, ASCT and maintenance therapy with DARZALEX and lenalidomide.

About DARZALEXJanssen is committed to exploring the potential of DARZALEX (daratumumab) for patients with multiple myeloma across the spectrum of the disease. DARZALEX has been approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.

DARZALEX has become a backbone therapy in the treatment of multiple myeloma, having been used in the treatment of more than 150,000 patients worldwide and more than 68,000 patients in the U.S. alone since its U.S. FDA approval in 2015. DARZALEX is the first CD38-directed antibody approved globally to treat multiple myeloma.

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.3 DARZALEX binds to CD38 and inhibits tumor cell growth causing myeloma cell death.4 DARZALEX may also have an effect on normal cells.5 Data across eight Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that DARZALEX-based regimens resulted in significant improvement in progression-free survival and/or overall survival.5,6,7,8,9,10,11,12

About Multiple MyelomaMultiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.13,14When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow. In 2020, it is estimated that more than 32,000 people will be diagnosed and close to 13,000 will die from the disease in the U.S.15 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.15

DARZALEXINDICATIONS

DARZALEX(daratumumab) is indicated for the treatment of adult patients with multiple myeloma:

DARZALEXIMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

DARZALEX is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

DARZALEX can cause severe and/or serious infusion-related reactions including anaphylactic reactions. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week1 (16mg/kg) infusion, 2% with the Week2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5hours (range: 0 to 73hours). Nearly all reactions occurred during infusion or within 4hours of completing DARZALEX. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, laryngeal edema, and pulmonary edema. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension.

When DARZALEX dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75months (range: 2.4 to 6.9months), upon re-initiation of DARZALEX, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16mg/kg dose at Week 1 split over two days, ie, 8mg/kg on Day1 and Day2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day1 of Week1, 4% on Day2 of Week1, and 8% with subsequent infusions.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Interference With Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive Indirect Antiglobulin Test may persist for up to 6months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia and Thrombocytopenia

DARZALEX may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX until recovery of neutrophils or for recovery of platelets.

Interference With Determination of Complete Response

Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX can cause fetal harm when administered to a pregnant woman. DARZALEX may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX and for 3 months after the last dose.

The combination of DARZALEX with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women, because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

ADVERSE REACTIONS

The most frequently reported adverse reactions (incidence 20%) were: upper respiratory infection, neutropenia, infusionrelated reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (40%) with DARZALEX are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.

Please click hereto see the full Prescribing Information.

DARZALEX FASPRO INDICATIONS DARZALEXFASPRO is indicated for the treatment of adult patients with multiple myeloma:

DARZALEX FASPROIMPORTANT SAFETY INFORMATIONCONTRAINDICATIONS

DARZALEX FASPRO(daratumumab and hyaluronidase-fihi) is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Other Administration Reactions

Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO.

Systemic Reactions

In a pooled safety population of 490patients who received DARZALEX FASPROas monotherapy or in combination, 11% of patients experienced a systemic administration-related reaction (Grade 2: 3.9%, Grade 3: 1.4%). Systemic administration-related reactions occurred in 10% of patients with the first injection, 0.2% with the second injection, and cumulatively 0.8% with subsequent injections. The median time to onset was 3.7hours (range: 9minutes to 3.5days). Of the 84systemic administration-related reactions that occurred in 52patients, 73(87%) occurred on the day of DARZALEX FASPROadministration. Delayed systemic administration-related reactions have occurred in less than 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension and tachycardia. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritis, chills, vomiting, nausea, and hypotension.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO.Consider administering corticosteroids and other medications after the administration of DARZALEX FASPROdepending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Local Reactions

In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade2 reactions in 0.6%. The most frequent (>1%) injection-site reaction was injection site erythema. These local reactions occurred a median of 7minutes (range: 0minutes to 4.7days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.

NeutropeniaDaratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPROuntil recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPROhigher rates of Grade 3-4 neutropenia were observed.

ThrombocytopeniaDaratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPROuntil recovery of platelets.

Embryo-Fetal ToxicityBased on the mechanism of action, DARZALEX FASPROcan cause fetal harm when administered to a pregnant woman. DARZALEX FASPROmay cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPROand for 3months after the last dose.

The combination of DARZALEX FASPROwith lenalidomide is contraindicated in pregnant women, because lenalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide prescribing information on use during pregnancy.

Interference with Serological TestingDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted.

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO.Type and screen patients prior to starting DARZALEX FASPRO.

Interference with Determination of Complete Response

Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPROtreated patients with IgG kappa myeloma protein.

ADVERSE REACTIONSThe most common adverse reaction (20%) with DARZALEX FASPROmonotherapy is: upper respiratory tract infection. The most common adverse reactions with combination therapy (20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, pyrexia, cough, muscle spasms, back pain, vomiting, upper respiratory tract infection, peripheral sensory neuropathy, constipation, and pneumonia.

The most common hematology laboratory abnormalities (40%) with DARZALEX FASPROare decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Please see full Prescribing Information atwww.DARZALEX.com.

About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at http://www.janssen.com. Follow us at http://www.twitter.com/JanssenGlobal and http://www.twitter.com/JanssenUS. Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Cautions Concerning Forward-Looking StatementsThis press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding DARZALEX. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Biotech, Inc., Janssen Research & Development, LLC, or any of the other Janssen Pharmaceutical Companies, and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in the company's most recently filed Quarterly Report on Form 10-Q, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov, http://www.jnj.comor on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

1 Kaufman, JL et al. Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of GRIFFIN After 12 Months of Maintenance Therapy. Abstract #549. To be presented at 2020 American Society of Hematology Annual Meeting. 2Voorhees, PM et al. Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients with Transplant-eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Efficacy and Safety Analysis of the Safety Run-in Population of GRIFFIN. Abstract #3243. To be presented at 2020 American Society of Hematology Annual Meeting. 3Janssen Research & Development, LLC. Study Comparing Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone (D-RVd) Versus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Subjects With Newly Diagnosed Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2016 August 22]. Available at: https://clinicaltrials.gov/ct2/show/NCT02874742 Identifier: NCT02874742. 4Fedele G et al. CD38 Ligation in Peripheral Blood Mononuclear Cells of Myeloma Patients Induces Release of Protumorigenic IL-6 and Impaired Secretion of IFN Cytokines and Proliferation. Mediators Inflamm. 2013;564687. 5Janssen Research & Development, LLC. A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009?term=mmy3003&rank=1 Identifier: NCT02136134. 6Janssen Research & Development, LLC. Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134?term=mmy3004&rank=1 Identifier: NCT02076009. 7Janssen Research & Development, LLC. A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383?term=mmy3006 Identifier: NCT02541383. 8Janssen Research & Development, LLC. A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479?term=mmy3007&rank=1 Identifier: NCT02195479. 9 Janssen Research & Development, LLC. Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=mmy3008&rank=1 Identifier: NCT02252172. 10Janssen Research & Development, LLC. A Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-Dose Therapy (Asia Pacific Region). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812?term=MMY3011&rank=1 Identifier: NCT03217812. 11European Myeloma Network. Compare Progression Free Survival Btw Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03180736?term=MMY3013&rank=2 Identifier: NCT03180736. 12Amgen. Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1 Identifier: NCT03158688. 13Kumar, SK et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012 Jan; 26(1):149-57. 14American Cancer Society. "What Is Multiple Myeloma?" Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed June 2019. 15American Cancer Society. "Key Statistics About Multiple Myeloma." Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed January 2020.

Media contacts:Bernadette King Phone: +1 215-778-3027

Satu Glawe Phone: +49 172-294-6264

Investor Relations: Jennifer McIntyre Phone: +1 732-524-3922

U.S. Medical Inquiries:+1 800-526-7736

SOURCE The Janssen Pharmaceutical Companies of Johnson & Johnson

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New DARZALEX (daratumumab) Data from GRIFFIN Study Show Deeper and Longer Responses in Patients with Newly Diagnosed Multiple Myeloma - PRNewswire

CRISPR Therapeutics and Vertex Present New Data for Investigational CRISPR/Cas9 Gene-Editing Therapy, CTX001 at American Society of Hematology Annual…

December 05, 2020 12:30 ET | Source: CRISPR Therapeutics AG

- Beta thalassemia: All seven patients were transfusion independent with 3 to 18 months of follow-up after CTX001 infusion -

- Sickle cell disease: All three patients were free of vaso-occlusive crises with 3 to 15 months of follow-up after CTX001 infusion -

- Nineteen patients have been dosed with CTX001 across both programs -

- The New England Journal of Medicine publishes CTX001 manuscript containing the first report of investigational use of CRISPR/Cas9-based gene editing to treat inherited diseases in humans -

ZUG, Switzerland and CAMBRIDGE, Mass. and BOSTON, Dec. 05, 2020 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data on a total of 10 patients treated with the investigational CRISPR/Cas9-based gene-editing therapy, CTX001, that show a consistent and sustained response to treatment. All seven patients with transfusion-dependent beta thalassemia (TDT), including three who have either a severe or b0/b0 genotype, were transfusion independent at last follow-up and all three patients with sickle cell disease (SCD) were free of vaso-occlusive crises (VOCs) from CTX001 infusion through last follow-up. These data will be presented during the Scientific Plenary at the annual ASH Meeting and Exposition on December 6, 2020. A summary of the results from the CLIMB-111 and CLIMB-121 Phase 1/2 clinical studies is provided below.

The companies also announced that The New England Journal of Medicine (NEJM) has published an independently peer-reviewed article entitled CRISPR-Cas9 Gene Editing for Sickle Cell Disease and Thalassemia. The article includes detailed information on the first patient with TDT enrolled in CLIMB-111 and the first patient with severe SCD enrolled in CLIMB-121, at 18 and 15 months of follow-up, respectively.

CTX001 is being investigated in these two ongoing Phase 1/2 clinical trials as a potential one-time curative therapy for patients suffering from TDT and severe SCD.

We are pleased with the data presented at ASH, which demonstrate potential benefit and durability among a larger population of patients with transfusion-dependent beta thalassemia and sickle cell disease, said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. Additionally, the NEJM case study is the first peer-reviewed journal publication for our CRISPR/Cas9 gene therapy, CTX001. Together this is further validation of the potential of CTX001 to become a best-in-class therapy. We plan to continue the rapid advancement of our clinical trials to bring these much-needed therapies to patients.

These are the first published results from CRISPR/Cas9 therapy in people with a genetic disease and represent an important milestone in medicine and for our collaboration with CRISPR Therapeutics. Most importantly, these data represent a critical step in our effort to bring transformative and potentially curative therapies to patients, said Reshma Kewalramani, M.D., Chief Executive Officer and President, Vertex. With clinical proof-of-concept for both beta thalassemia and sickle cell disease and 19 patients dosed, we look forward to continued efforts to bring our investigational treatment to patients living with TDT and SCD as quickly as we can.

Our vision with this approach is to use the patients own stem cells to provide a transformative treatment for these diseases, something almost unimaginable a few years ago, said Dr. Haydar Frangoul, M.D., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute, HCA Healthcares TriStar Centennial Medical Center. With these data in 10 patients, we can see the potential to fulfill this vision. With more data and longer duration of follow-up, we will hopefully confirm that we have a durable therapy that may transform the lives of many patients.

CLIMB-111 Trial in TDT: Updated Results A total of 13 patients with TDT have been dosed with CTX001, including eight additional patients since the last update in June 2020.

The seven patients with TDT reported at ASH are patients who had reached at least three months of follow-up after CTX001 dosing and therefore could be assessed for initial safety and efficacy. All seven patients showed a similar pattern of response, with rapid and sustained increases in total hemoglobin, fetal hemoglobin and transfusion independence at last analysis.

All seven patients were transfusion independent with follow-up ranging from three to 18 months after CTX001 infusion, with normal to near normal total hemoglobin levels at last visit, including total hemoglobin from 9.7 to 14.1 g/dL and fetal hemoglobin from 40.9% to 97.7%.

Bone marrow allelic editing data collected from four patients with six months of follow-up and from one patient with 12 months of follow-up after CTX001 infusion demonstrated a durable effect.

The safety data from all seven patients were generally consistent with an autologous stem cell transplant and myeloablative conditioning. There were four serious adverse events (SAEs) considered related or possibly related to CTX001 reported in one patient: headache, hemophagocytic lymphohistiocytosis (HLH), acute respiratory distress syndrome and idiopathic pneumonia syndrome. All four SAEs occurred in the context of HLH and have resolved. The majority of non-serious adverse events were considered mild to moderate.

CLIMB-121 Trial in Severe SCD: Updated Results A total of six patients with SCD have been dosed with CTX001, including four additional patients since the last update in June 2020.

The three patients reported at ASH are patients who had reached at least three months of follow-up after CTX001 dosing and therefore could be assessed for initial safety and efficacy. All three patients showed a similar pattern of response, with rapid and sustained increases in total hemoglobin and fetal hemoglobin, as well as elimination of VOCs through last analysis.

All three patients remained VOC-free with follow-up ranging from three to 15 months after CTX001 infusion and had hemoglobin levels in the normal to near normal range at last visit, including total hemoglobin from 11.5 to 13.2 g/dL and fetal hemoglobin levels from 31.3% to 48.0%.

Bone marrow allelic editing data collected from one patient with six months of follow-up and from one patient with 12 months of follow-up after CTX001 infusion demonstrated a durable effect.

The safety data from all three patients were generally consistent with an autologous stem cell transplant and myeloablative conditioning. There were no SAEs considered related to CTX001, and the majority of non-serious adverse events were considered mild to moderate.

About CTX001 CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patients hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission for both TDT and SCD, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for SCD.

CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex. Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About CLIMB-111 The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121 The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About the Gene-Editing Process in These Trials Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patients cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease and for safety.

About the CRISPR-Vertex Collaboration CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. CRISPR Therapeutics and Vertex will jointly develop and commercialize CTX001 and equally share all research and development costs and profits worldwide.

About CRISPR Therapeutics CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Cambridge, Massachusetts, and business offices in San Francisco, California and London, United Kingdom. For more information, please visit http://www.crisprtx.com.

CRISPR Therapeutics Forward-Looking Statement This press release may contain a number of forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements made by Dr. Kulkarni, Dr. Kewalramani and Dr. Frangoul in this press release, as well as statements regarding CRISPR Therapeutics expectations about any or all of the following: (i) the safety, efficacy and clinical progress of CRISPR Therapeutics various clinical programs including CTX001; (ii) the status of clinical trials (including, without limitation, the expected timing of data releases) related to product candidates under development by CRISPR Therapeutics and its collaborators, including expectations regarding the data that are being presented in this press release, at the annual ASH Meeting and Exposition, and in the NEJM article; (iii) the expected benefits of CRISPR Therapeutics collaborations; and (iv) the therapeutic value, development, and commercial potential of CRISPR/Cas9 gene editing technologies and therapies. Without limiting the foregoing, the words believes, anticipates, plans, expects and similar expressions are intended to identify forward-looking statements. Although CRISPR Therapeutics believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, existing and prospective investors are cautioned that forward-looking statements are inherently uncertain, are neither promises nor guarantees and not to place undue reliance on such statements, which speak only as of the date they are made. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: that preliminary data from any clinical trial and initial data from a limited number of patients (as is the case with CTX001 at this time) may not be indicative of final or future trial results; that CTX001 clinical trial results may not be favorable or may not support registration or further development; potential impacts due to the coronavirus pandemic, such as to the timing and progress of clinical trials; that future competitive or other market factors may adversely affect the commercial potential for CTX001; uncertainties regarding the intellectual property protection for CRISPR Therapeutics technology; and those risks and uncertainties described under the heading Risk Factors in CRISPR Therapeutics most recent annual report on Form 10-K, quarterly report on Form 10-Q, and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission, which are available on the SEC's website at http://www.sec.gov. CRISPR Therapeutics disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law.

CRISPR THERAPEUTICS word mark and design logo and CTX001 are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.

About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of genetic and cell therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 11 consecutive years on Science magazine's Top Employers list and a best place to work for LGBTQ equality by the Human Rights Campaign. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Vertex Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements made by Dr. Samarth Kulkarni, Dr. Reshma Kewalramani and Dr. Haydar Frangoul in this press release and statements regarding the expectations and plans to present data at the annual ASH Meeting and Exposition, the development, including expected timeline for development, updated data on patients treated to date and new data on additional patients, and the potential benefits and curative therapy of CTX001, our plans and expectations for our clinical trials and clinical trial sites, including statements regarding patient enrollment, and the status of our clinical trials of our product candidates under development by us and our collaborators, including activities at the clinical trial sites and potential outcomes. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from a limited number of patients may not be indicative of final clinical trial results, that data from the company's development programs, including its programs with its collaborators, may not support registration or further development of its compounds due to safety, efficacy, or other reasons, that the COVID-19 pandemic may impact the status or progress of our clinical trials and clinical trial sites and the clinical trials and clinical trial sites of our collaborators, including patient enrollment, and other risks listed under the heading Risk Factors in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at http://www.sec.gov and available through the company's website at http://www.vrtx.com. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

CRISPR Therapeutics Investor Contact: Susan Kim, +1 617-307-7503 susan.kim@crisprtx.com

CRISPR Therapeutics Media Contact: Rachel Eides WCG on behalf of CRISPR +1 617-337-4167 reides@wcgworld.com

Vertex Pharmaceuticals Incorporated Investors: Michael Partridge, +1 617-341-6108 or Zach Barber, +1 617-341-6470 or Brenda Eustace, +1 617-341-6187

Media: mediainfo@vrtx.com or U.S.: +1 617-341-6992 or Heather Nichols: +1 617-839-3607 or International: +44 20 3204 5275

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CRISPR Therapeutics and Vertex Present New Data for Investigational CRISPR/Cas9 Gene-Editing Therapy, CTX001 at American Society of Hematology Annual...

Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease – Albany Times Union

Mo Ebrahimkhani,University of Pittsburgh

Dec. 7, 2020Updated: Dec. 7, 2020 2:02p.m.

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

(THE CONVERSATION) Takeaways

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Scientists have made progress growing human liver in the lab.

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The challenge has been to direct stems cells to grow into a mature, functioning adult organ.

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This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue.

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When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.

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 field called synthetic biology focused 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 organs figuring 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.

Tissues and organs made by genetic designs

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 chemicals like proteins or sugar in 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 students Jeremy Velazquez and Ryan LeGraw used 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.

Liver in a dish

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 genes and the resulting proteins that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny several millimeters in width but 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.

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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 bile a 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.

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/genetic-engineering-transformed-stem-cells-into-working-mini-livers-that-extended-the-life-of-mice-with-liver-disease-151089.

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Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease - Albany Times Union