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Dolly the Sheep: ’90s Media Sensation – Mental Floss

It was Saturday, February 22, 1997, and Scottish researchers Ian Wilmut and Keith Campbell were expecting a final moment of calm before the results of their unprecedented scientific experiment were announced to the world.

The team had kept the breakthrough under wraps for seven months while they waited for their paper to be published in the prestigious journal Nature. Confidential press releases had gone out to journalists with the strict instruction not to leak the news before February 27.

But that night, the team was tipped off that journalist Robin McKie was going to break the story the very next day in the British newspaper The Observer.

Wilmut and Campbell raced to the lab at the Roslin Institute on Sunday morning as McKie's story hit the media like a thunderbolt. International news outlets had already started swarming at the institute for access to Wilmut and Campbell's creation: Dolly the sheep, the world's first mammal successfully cloned from a single adult cell. Shielded from the general public, she stuck her nose through the fence and munched calmly on the hay in her pen, unperturbed by the horde of news photographers. Dolly, a woolly, bleating scientific miracle, looked much like other sheep, but with a remarkable genetic difference.

By the end of that Sunday, February 23, nearly every major newspaper in the world carried headlines about Dolly the sheep.

Born on July 5, 1996, Dolly was cloned by Wilmut and Campbell's team at the Roslin Institute, a part of the University of Edinburgh, and Scottish biotechnology company PPL Therapeutics. The scientists cloned Dolly by inserting DNA from a single sheep mammary gland cell into an egg of another sheep, and then implanting it into a surrogate mother sheep. Dolly thus had three mothersone that provided the DNA from the cell, the second that provided the egg, and the third that carried the cloned embryo to term. Technically, though, Dolly was an exact genetic replica of only the sheep from which the cell was taken.

Following the announcement, the Roslin Institute received 3000 phone calls from around the world. Dolly's birth was heralded as one of the most important scientific advances of the decade.

But Dolly wasn't science's first attempt at cloning. Researchers had been exploring the intricacies of cloning for almost a century. In 1902, German embryologists Hans Spemann and Hilda Mangold, his student, successfully grew two salamanders from a single embryo split with a noose made up of a strand of hair. Since then, cloning experiments continued to become more sophisticated and nuanced. Several laboratory animal clones, including frogs and cows, were created before Dolly. But all of them had been cloned from embryos. Dolly was the first mammal to be cloned from a specialized adult cell.

Embryonic stem cells, which form right after fertilization, can turn into any kind of cell in the body. After they modify into specific types of cells, like neurons or blood cells, they're call specialized cells. Since the cell that gave rise to Dolly was already specialized for its role as a mammary gland cell, most scientists thought it would be impossible to clone anything from it but other mammary gland cells. Dolly proved them wrong.

Many scientists in the '90s were flabbergasted. Dollys advent showed that specialized cells could be used to create an exact replica of the animal they came from. It means all science fiction is true, biology professor Lee Silver of Princeton University told The New York Times in 1997.

The Washington Post reported that "Dolly, depending on which commentator you read, is the biggest story of the year, the decade, even the century. Wilmut has seen himself compared with Galileo, with Copernicus, with Einstein, and at least once with Dr. Frankenstein."

Scientists, lawmakers, and the public quickly imagined a future shaped by unethical human cloning. President Bill Clinton called for review of the bioethics of cloning and proposed legislation that would ban cloning meant ''for the purposes of creating a child (it didn't pass). The World Health Organization concluded that human cloning was "ethically unacceptable and contrary to human integrity and morality" [PDF]. A Vatican newspaper editorial urged governments to bar human cloning, saying every human has "the right to be born in a human way and not in a laboratory."

Meanwhile, some scientists remained unconvinced about the authenticity of Wilmut and Campbells experiment. Norton Zinder, a molecular genetics professor at Rockefeller University, called the study published in Nature "a bad paper" because Dolly's genetic ancestry was not conclusive without testing her mitochondriaDNA that is passed down through mothers. That would have confirmed whether Dolly was the daughter of the sheep that gave birth to her. In The New York Times, Zinder called the Scottish pair's work ''just lousy science, incomplete science." But NIH director Harold Varmus toldthe Times that he had no doubt that Dolly was a clone of an adult sheep.

Because she was cloned from a mammary gland cell, Dolly was nameddad joke alertafter buxom country music superstar Dolly Parton. (Parton didnt mind the attribution.) Like her namesake, Dolly the sheep was a bona fide celebrity: She posed for magazines, including People; became the subject of books, journal articles, and editorials; had an opera written about her; starred in commercials; and served as a metaphor in an electoral campaign.

And that wasn't all: New York Times reporter Gina Kolata, one of the first journalists to give readers an in-depth look at Dolly, wroteClone: The Road to Dolly, and the Path Ahead and contrasted the animal's creation with the archetypes in Frankenstein and The Island of Dr. Moreau. American composer Steve Reich was so affected by Dolly's story that he featured it in Three Tales, a video-opera exploring the dangers of technology.

The sheep also became an inadvertent political player when the Scottish National Party used her image on posters to suggest that candidates of other parties were all clones of one another. Appliance manufacturer Zanussi used her likeness for a poster with her name and the provocative caption "The Misappliance of Science" (the poster was later withdrawn after scientists complained). In fact, so widespread was the (mis)use of her name that her makers eventually trademarked it to stop the practice.

Following Dolly, many larger mammals were cloned, including horses and bulls. Roslin Biomed, set up by the Roslin Institute to focus on cloning technology, was later sold to the U.S.-based Geron Corporation, which combined cloning technology with stem cell research. But despite her popularityand widespread fearDolly's birth didn't lead to an explosion in cloning: Human cloning was deemed too dangerous and unethical, while animal cloning was only minimally useful for agricultural purposes. The sheep'sreal legacy is considered to be the advancement in stem cell research.

Dollys existence showed it was possible to change one cells gene expression by swapping its nucleus for another. Stem cell biologist Shinya Yamanaka told Scientific American that Dollys cloning motivated him to successfully develop stem cells from adult cells. He later won a Nobel Prize for his results, called induced pluripotent stem cells (iPS) because they're artificially created and can have a variety of uses. They reduced the need for embryonic stem cells in research, and today, iPS cells form the basis for most stem cell research and therapies, including regenerative medicine.

Dolly had sixoffspring, and led a productive, sociable life with many human fans coming to visit her. In 2003, a veterinary examination showed that Dolly had a progressive lung disease, and she was put down. But four clonescreated from the same cell line in 2007 faced no such health issues and aged normally.

Dolly is still a spectacle, though, nearly 25 years after her creation: Her body was taxidermied and puton display at the National Museum of Scotland in Edinburgh.

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Dolly the Sheep: '90s Media Sensation - Mental Floss

Regeneron, Pfizer and BioNTech Accused of Infringing Allele Patent in Connection with COVID-19 Technologies – IPWatchdog.com

Only through use of mNeonGreen were [Pfizer and BioNTech] able to develop and test the BNT162 vaccine candidate at lightspeed, making them first to market [and] earning them an immediate $400 million in grants and over $4 billion in sales of the vaccine to- date. Allele Complaint

Allele Biotechnology and Pharmaceuticals, Inc. (Allele) has accused Regeneron Pharmaceuticals, Inc. (Regeneron); Pfizer, Inc. (Pfizer); and BioNTech SE and BioNTech US, Inc. (collectively BioNTech) for allegedly infringing U.S. Patent No. 10,221,221 (the 221 patent), which is directed to an artificial flourescent, i.e. mNeonGreen, used for testing COVID-19 assays against vaccine candidates. Allele argues that Regeneron, Pfizer and BioNTech have been infringing the 221 patent by taking mNeonGreen for their own unauthorized commercial testing and development.

Regeneron has been in the news lately for famously providing the antibody cocktail given to President Donald Trump shortly after he tested positive for COVID-19 last week. The cocktail is name in the complaint as one of the allegedly infringing technologies.

The 221 patent, titled Monomeric Yellow-Green Fluorescent Protein from Cephalochordate, was assigned to Allele and directed to high performance monomeric yellow-green fluorescent proteins. Although mNeonGreen was Alleles breakthrough in fluorescent protein technology, Allele has many other achievements, including advances in RNA interference, Fluorescent Proteins, Induced Pluripotent Stem Cells (iPSCs), Genome Editing, and camelid derived Single Domain Antibodies. Most recently, Allele has also been actively engaged in combating COVID-19, initiating impactful diagnostic and therapeutic platforms premised on speed, accuracy, and sensitivity. Alleles mNeonGreen technology has been licensed to hundreds of organizations and universities. As asserted by Allele, mNeonGreen facilitates quick, targeted, and precise receptor research, including for potential therapeutics to treat COVID-19.

Allele filed a Complaint against Regeneron in the U.S. District Court for the Southern District of New York alleging that Regeneron has been using Alleles patented mNeonGreen technology. Allele cited multiple published articles and papers written by Regeneron representatives. The Complaint noted that Regeneron did not have a license to use Alleles mNeonGreen technology, despite Alleles consistent showing that it is willing to license its mNeonGreen technology on reasonable terms in order to help facilitate the use of that protein by third parties in their efforts to develop new and essential technologies. Also, according to the Complaint, Allele sought to discuss licensing arrangements with Regeneron after learning of the infringement of the 221 patent, but Regeneron ignored Alleles attempts.

The Complaint asserted that Regeneron directly infringed the mNeonGreen technology claimed in the 221 patent and, by way of its publications, press releases, and other papers, caused others to directly infringe the mNeonGreen technology claimed in the 221 patent. Thus, Allele asked the court, in part, for: (1) a finding that the 221 patent is valid and enforceable, (2) a judgment that Regeneron had infringed, actively induced infringement of, and/or contributed to the infringement of one or more claims of the 221 patent, (3) a judgment that Regenerons infringement was willful, and (4) an award of damages or other monetary relief to adequately compensate Allele for Regenerons infringement of the 221 patent, and such damages be trebled under 35 U.S.C. 284 and awarded to Allele, with pre-judgment and post-judgment interest as allowed by law.

The Complaint against Pfizer and BioNTech (collectively, Defendants) was filed in the U.S. District Court for the Southern District of California and alleges that the Defendants infringed Alleles 221 patent using mNeonGreen throughout their COVID-19 vaccine trials. Pfizer was engaged with BioNTech in the development of their BNT162 MRNA-based vaccine candidate. Allele asserted that [o]nly through use of mNeonGreen were Defendants able to develop and test the BNT162 vaccine candidate at lightspeed making them first to market, earning them an immediate $400 million in grants and over $4 billion in sales of the vaccine to- date [which]was simply the downstream benefit that Defendants enjoyed (and presumably the world will enjoy from the vaccine) from their choice to use Alleles mNeonGreen.

According to the Complaint, BioNTech adopted Alleles mNeonGreen technology in its COVID-19 vaccine trial and literally infringed claims 1, 2, 4 and 5 of the 221 patent. Allele asserted that it has not granted the Defendants authorization, license, or permission to practice the inventions claimed in the 221 Patent. Allele also asserted that Defendants infringement was willful because the defendants had actual knowledge of the 221 Patent and the obvious risk of infringement by continued use of mNeonGreen throughout their development of their COVID-19 vaccine candidate in the United States. Thus, Allele requested, in part, that the court (1) find that the 221 Patent has been infringed by the Defendants in violation of 35 U.S.C. 271, (2) find that the Defendants infringement of the 221 Patent was been willful, (3) award adequate damages to compensate Allele for the Defendants infringement, and (4) an award of treble damages for the period of any willful infringement by the Defendants pursuant to 35 U.S.C. 284.

Image Source: Deposit Photos Author: Rewat Image ID: 358544690

Rebecca Tapscott is an intellectual property attorney who has joined IPWatchdog as our Staff Writer. She received her Bachelor of Science degree in chemistry from the University of Central Florida and received her Juris Doctorate in 2002 from the George Mason School of Law in Arlington, VA.

Prior to joining IPWatchdog, Rebecca has worked as a senior associate attorney for the Bilicki Law Firm and Diederiks & Whitelaw, PLC. Her practice has involved intellectual property litigation, the preparation and prosecution of patent applications in the chemical, mechanical arts, and electrical arts, strategic alliance and development agreements, and trademark prosecution and opposition matters. In addition, she is admitted to the Virginia State Bar and is a registered patent attorney with the United States Patent and Trademark Office. She is also a member of the American Bar Association and the American Intellectual Property Law Association.

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Regeneron, Pfizer and BioNTech Accused of Infringing Allele Patent in Connection with COVID-19 Technologies - IPWatchdog.com

Proposition 14: With Handful of Cures, Calif. Stem Cell Agency Has Mixed Record. Will Voters Pony Up Another $5.5 Billion? – KQED

A Yes vote authorizes the state to sell $5.5 billion in general obligation bonds primarily for stem cell research and the development of new medical treatments in California. A No vote would mean the state's stem cell research agency will probably shut down by 2023.

In the ramp-up to the 2004 election, a California TV viewer may have come across the popular actor Michael J. Fox urging her to vote Yes on a state proposition. His voice slurred faintly by Parkinsons disease, he still sounded wry, boyish and familiar.

My most important role lately is as an advocate for patients and for finding new cures for diseases, said Fox, eyes level with the camera. Californias Stem Cell Research Initiative 71 will support research to find cures for diseases that affect millions of people, including cancer, diabetes, Alzheimer's and Parkinson's.

Within that 30-second spot, Fox, diagnosed at age 29 with a neurodegenerative disorder that typically does not strike until after 60, used the word "cures" three times.

Proposition 71, which passed with 59% of the vote, authorized the sale of $3 billion in bonds to create an agency that funded stem cell research. The successful campaign grew out of a time, in the early 2000s, when the promise of stem cell and regenerative medicine excited both scientists and the public.

Whether the project has lived up to that promise is a matter of opinion. How voters view the record of the agency may go a long way in their decision whether or not to replenish the fund, which is fast running out of money, with an additional $5.5 billion, to be raised with new bonds authorized by Proposition 14, now on the ballot.

President Bush A Demon to Attack

Scientists since the1800s have known about stem cells, which are not yet dedicated to any particular anatomical function and have the potential to become nerve cells, blood cells, skin cells or any other type. They are found in blastocysts, which are human embryos four to five days after fertilization, and in a few areas, such as bone marrow and gonads, in adults.

In the late 1990s, researchers developed ways to steer the development of these cells, and the possibilities for improving medicine seemed endless. If malfunctioning cells were at the root of a particular disease, could new healthy cells tailored to the job fix what was wrong? Scientists and many members of the public were eager to find out.

Anti-abortion groups, however, a key constituency of President George W. Bush, opposed the research, and in 2001 he limited federal funding to a few existing lines of embryonic stem cells, severely curtailing research.

Some in the state of California wanted to get around Bushs restrictions, and Proposition 71 was born.

"(T)hey had this demon they could attack in the campaign the Bush administration," said David Jensen, author of "California's Great Stem Cell Experiment," who also writes the blog California Stem Cell Report. "They could say, 'This is a great opportunity, and the only way we're going to get it done is to do it here in California.'"

The measure created the California Institute for Regenerative Medicine. The stem cell research agency is unique in the U.S.

"No other state has done this kind of level of funding and focus on this kind of thing, said Jensen. It's a really cutting-edge area of science."

A Few Successes

The pace of innovation has been slower than many hoped. As it turned out, grand discoveries were not around the corner, and to date there is no widespread stem cell treatment approved for the public. To date, CIRM has funded more than 64 trials directly and aided in 31 more. Not all have or will result in treatments.

But despite the lack of a marquee cure like one for Alzheimers or Parkinsons, the agency has seen some notable triumphs.

"Probably one of the most spectacular successes they have certainly so far," said Jensen, "is clinical trials that have saved the lives of what they say are 40 children."

Those children were born with severe combined immunodeficiency (SCID), commonly known as "bubble baby syndrome," a rare, generally fatal condition in which a child is born without a working immune system. An FDA-approved gene therapy that grew out of CIRM-funded research can now cure the disease by taking a patients own blood stem cells and modifying them to correct the SCID mutation. The altered cells generate new, healthy blood cells and repair the immune system.

The FDA has also approved two drugs for rare blood cancers that were developed with CIRM funds.

Sandra Dillon, a graphic designer in San Diego, credits one of the drugs with saving her life. She was diagnosed when she was just 28, in 2006. Her doctors told her they would try to manage her symptoms, but that she was going to get progressively sicker.

"Even just the idea of a cure or getting better wasn't even on the table back then," said Dillon, who is featured in ads for the Yes on 14 campaign.

"I remember just praying and begging into the universe, please, someone just look at my disease, please someone help, who is going to look at this thing.

By 2010, Dillon was extremely ill. She connected with a doctor at UC San Diego who received early-stage funding from CIRM and told her she could take part in clinical trials.

"For the first time, there was this moment of, 'Oh, my gosh! There are researchers doing something. And it could help me and I can get access to it.' It was amazing."

The drug received FDA approval in 2019, and today Dillons cancer has retreated to the point where she can live a normal life.

"I love that I am not tethered to a hospital anymore. I can go out on long backpacking trips and hiking and surfing," she said. "I am a completely different person with this drug. And I have a whole future ahead of me."

The original funding raised by Proposition 71 is running out. Proposition 14 would authorize the sale of a new bond to refill the agency piggy bank. Gov. Gavin Newsom, the UC Board of Regents, and scores of patient advocacy groups also support the measure.

Many newspaper editorial boards, however, oppose the proposition, including the San Francisco Chronicle, Mercury News and Los Angeles Times.

Right now the state still owes about $1 billion toward the debt created by Proposition 71. If Proposition 14 passes, the yearly price tag to pay off the new bond would be about $260 million per year for about 30 years.

One of the selling points of the original proposition was the potential for the state to earn big money in royalties from the treatments it helped develop, says Jeff Sheehy, an HIV patient advocate and the only CIRM board member to oppose Proposition 14.

"The promises were made that this would pay for itself. We would be able to pay back the bonds with the money we would get from royalties, etc., etc.

That has not worked out as envisioned: CIRM estimates it has received less than $500,000 in royalties. Early this year, Forty Seven, a company whose therapies were heavily funded by CIRM, sold to Gilead for $4.9 billion. While millions went to various researchers, neither CIRM nor the state of California received anything.

One of the flaws in the original measure is that we [the agency] cannot hold stock in the products that we develop," says Sheehy. "And that's because the California Constitution says that the state of California cannot, as a government entity, hold equity.

Proposition 14 makes it impossible for the state to use profits from its investment on, say, schools or other funding priorities. Instead, any royalties earned must be fed back into programs to make CIRM-funded treatments more affordable.

"What it does is it basically takes all of our returns that we get from this and gives it back to the pharmaceutical and biotech companies," said Sheehy. "It becomes just a blatant giveaway to these companies when we should be requiring access and requiring fair pricing."

Sheehy says he supports medical research, but doesn't like the state going into more debt to pay for it. The greater the state's obligations in bond money, which has to be paid back with interest, the less there is in the general fund, and Sheehy says the state has more pressing needs than stem cell research things like housing, education and transportation.

"The biggest and perhaps the most compelling reason why I feel so strongly that this is not a good idea is that we simply cannot afford it, he said. "If we think this is so important," asks Sheehy, "why don't we just don't pay for [this research] out of the general fund? It would be cheaper.

Opponents of Proposition 14 also point to longstanding complaints of conflicts of interest among the agency board. Most of the $3 billion distributed by the agency has gone to institutions with connections to board members. Critics say the structural conflicts of interest between the board and agency are not addressed in the new measure. Proposition 14 would balloon an already huge board of 29 members to 35.

Funding needs for stem cell research also are not as acute as they were back in 2004. The federal National Institutes of Health now funds some basic stem cell research, spending about $2 billion a year, with $321 million of that going toward human embryonic stem cell research. And private ventures, like nonprofits started by tech billionaires, are pouring more money into biotech.

The problem with assuming that, says Melissa King, executive director of Americans for Cures, the stem cell advocacy group behind the Yes on 14 campaign, is that CIRM fills a neglected funding need.

The NIH does not fund clinical trials at nearly the rate that CIRM can and has been, King said.

She says that's important because of what she calls the "Valley of Death," where promising early-stage research frequently fails to translate into promising treatments that can be tested in clinical-stage research. (What works well in a test tube often does not work well in an organism.) This weeding-out process is costly but necessary. And its where CIRM focused a lot of its effort.

The first- and maybe even second-phase clinical trials, its very difficult to get those funded, King said. It is too much of a risk for business to take on on its own. Venture [capital] isnt going there. Angel [funding] isnt going there.

What voters have to ask themselves, says writer Jensen, is whether stem cell funding is "a high priority for the state of California? Different people make different judgments about that."

CIRM supporters say if Prop. 14 doesn't pass, critical research will stall. Others say federal and private funding will step in and fill the gap.

Absent new funding, the institute expects it will wind down operations leading to a complete sundown in 2023.

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Proposition 14: With Handful of Cures, Calif. Stem Cell Agency Has Mixed Record. Will Voters Pony Up Another $5.5 Billion? - KQED

Woman who lost her partner to cancer last year set to run 10K in his memory – Warrington Guardian

A 29-YEAR-old who tragically lost her partner to cancer last year will be running 10K to raise vital funds for a blood cancer charity in his memory.

Hannah Kenyon, a teaching assistant from Culcheth, is taking part in the Tatton Park 10K this weekend, in tribute to her boyfriend, Jonny Williams, who died from Non-Hodgkins Lymphoma in February last year.

She will be raising money for Anthony Nolan, a charity which finds matching donors for people with blood cancer.

Speaking about her relationship with Jonny, Hannah said: "Jonny and I met at school, I always liked him but we didnt get together until we were in college.

"In March 2018, after having been together been for nine years, we bought our own home which we wanted to renovate and really make our own."

In July of that year, Jonny, who was an electrician, noticed lumps on his neck and started suffering from extreme abdominal pain.

After several trips to hospital, he was eventually diagnosed with stage four Non-Hodgkins Lymphoma.

Hannah recalled: "It was such a shock and Jonny had to start chemotherapy literally straight away.

"However, it wasnt working the way doctors had hoped and his cancer continued to progress.

"This was when a stem cell transplant was first mentioned - the goal was for chemotherapy to get Jonny into remission so he could then have a stem cell transplant, which would hopefully cure him."

With only one half brother and two half sisters, there was no chance of finding Jonny a match within his own family.

Anthony Nolan jumped into action and searched their register of potential stem cell donors for a special stranger who could save his life.

"We were told that Jonny had three potential donors," Hannah said.

"The day we found out, no words needed to be spoken to know how extremely lucky we felt, as I know there are people out there who desperately need a donor but dont have one."

After just a few months, Jonny and Hannah received the devastating news that Jonnys cancer had progressed, which meant that he was unable to have a transplant.

He died less than one week later.

Hannah explained: "It was and still is completely devastating, and at times it still feels like a blur.

"Jonny was such a positive person, Ive never known anyone so positive, and he tried to live as normal a life as possible during his illness.

"He wanted no fuss and always had hope and optimism for the future.

"Even though Jonny was unable to have a transplant, it is just unreal that three strangers were willing to help him.

"I know what its like to hear the news that someone out there is a match and is willing to save a life, which is why I just wont stop shouting about Anthony Nolan."

After Jonny's death, Hannah continued to renovate the house they had bought together.

She also started running and will now be putting on her trainers this weekend in aid of Anthony Nolan, alongside her friend, Sam.

"I know that Jonny would be buzzing about me doing this, he always was my number one fan," Hannah said.

"Sunday, I am sure, will be a really emotional day, but Ive got a playlist of Jonnys favourite songs that Im going to listen to whilst Im running that will keep me going."

You can sponsor Hannah at justgiving.com/fundraising/10kforjonny.

To find out more about Anthony Nolan, visit anthonynolan.org/events.

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Woman who lost her partner to cancer last year set to run 10K in his memory - Warrington Guardian

Q Stock; The Rise of BioRestorative Therapies Inc (OTCMKTS: BRTXQ) – MicroCap Daily

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BioRestorative Therapies Inc (OTCMKTS: BRTXQ) is heating up fast in recent trading and heading northbound again after several weeks of choppy waters. BioRestorative is among the most exciting stories in small caps that has attracted legions of new shareholders after the Company partnered on a new bankruptcy reorganization plan with one of its creditors Auctus Capital in which it would emerge from bankruptcy with the commons intact, ready to begin phase 2 trials and get BioRestorative back on a national stock exchange.

Penny stock speculators are accumulating BRTXQ as they wait for Judge Grossman to say the word EFFECTIVE. There is a lot of speculation on exactly when this will hapen considering the Judges schedule with holidays, COVID-19, and a logjam of cases on the docket. Interested shareholders are monitoring the developments on PACER.

BioRestorative Therapies Inc (OTCMKTS: BRTXQ) operating out of Melville, New York is a life sciences company focused on the development of regenerative medicine products and therapies using cell and tissue protocols, primarily involving adult (non-embryonic) stem cells. We develop therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs are: Disc/Spine Program (brtxDISCTM): Our lead cell therapy candidate, BRTX-100, is a product formulated from autologous cultured mesenchymal stem cells collected from bone marrow. The Company intends that the product will be used for the non-surgical treatment of protruding and bulging lumbar discs in patients suffering from chronic lumbar disc disease. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery. The Company has received clearance from the Food and Drug Administration to commence a Phase 2 clinical trial using BRTX-100 to treat chronic lower back pain due to degenerative disc disease related to protruding/bulging discs. Metabolic Program (ThermoStem): BioRestorative is developing a cell-based therapy to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (BAT). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in the body may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

BioRestorative Therapies is developing a cell-based therapy candidate to target obesity and metabolic disorders using brown adipose (fat) derived stem cells, or BADSC, to generate brown adipose tissue, or BAT. BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in animals may be responsible for additional caloric burning, as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

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BioRestorative owns a valuable intelectual property portfolio including unique international Stem Cell patents as well as 8 patents issued, in the United States and other countries, for the Companys brown fat technology related to BioRestoratives metabolic program (ThermoStem Program).

On March 20 BioRestorative filed a voluntary petition commencing a case under chapter 11 of title 11 of the U.S. Code in the United States Bankruptcy Court for the Eastern District of New York. The Companys chapter 11 case is being administered under the caption, In re: BioRestorative Therapies, Inc., Case No. 8-20-71757.

Initially intellectual property lawyer John Desmarais entered into a stalking horse agreement to buy the company. He would pay $500,000 to acquire the company, along with their assets (including the intellectual property). The deal with Desmarais fell apart in July when Auctus Capital partnered with the Company on a new bankruptcy reorganization plan in which the Company would emerge from bankruptcy with the commons intact, ready to begin their phase 2 trials and get BioRestorative back on a national stock exchange. On September 10th, a hearing was held for confirmation of the bankruptcy reorganization plan submitted jointly by the company and Auctus Capital Partners. Further detail will be added upon review of the judges order, but the plan and disclosure statement are available to Pacer or Pacermonitor subscribers.

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Currently on the move and running northbound again after several weeks of choppy waters BRTXQ is an exciting story developing in small caps; BioRestorative filed for bankruptcy protection in March but has partnered on a new bankruptcy reorganization plan with one of its creditors Auctus Capital in which the Company would emerge from bankruptcy with the commons intact, ready to begin their phase 2 trials and get BioRestorative back on a national stock exchange. Penny stock speculators are accumulating BRTXQ as they wait for Judge Grossman to say the word EFFECTIVE. There is a lot of speculation on exactly when this will happen considering the Judges schedule with holidays, COVID-19, and a logjam of cases on the docket. Interested shareholders are monitoring the developments on PACER.We will be updating on BioRestorative when more details emerge so make sure you are subscribed to Microcapdaily so you know whats going on with BioRestorative.

Disclosure: we hold no position in BRTXQ either long or short and we have not been compensated for this article.

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Q Stock; The Rise of BioRestorative Therapies Inc (OTCMKTS: BRTXQ) - MicroCap Daily

A Uniquely Patient-Focused Take on Treating AML in Older Adults – Medscape

A diagnosis of acute myeloid leukemia (AML) is particularly challenging in older adults, whose age makes them highly susceptible to the disease and treatment-related toxicity. To help patients and practitioners navigate the clinical decision-making process, the American Society of Hematology (ASH) convened an panel of experts who conducted a thorough review of the literature. The result of their work can be found in a new set of guidelines for the treatment of newly diagnosed AML in older adults.

Dr Mikkael Sekeres

Medscape spoke with Mikkael Sekeres, MD, chair of the ASH AML guideline panel and director of the Leukemia Program at Cleveland Clinic Taussig Cancer Institute. Sekeres shared the rationale behind the panel's key recommendations and the importance of keeping the patient's goals in mind.

Medscape: What is the average life expectancy of a 75-year-old developing AML compared with someone of the same age without AML?

Dr Sekeres: A 75-year-old developing AML has an average life expectancy measured in fewer than 6 months. Somebody who is 75 without leukemia in the United States has a life expectancy that can be measured in a decade or more. AML is a really serious diagnosis when someone is older and significantly truncates expected survival.

What is the median age at AML diagnosis in the United States?

About 67 years.

What are the biological underpinnings for poor outcomes in older AML patients?

There are a few of them. Older adults with AML tend to have a leukemia that has evolved from a known or unknown previous bone marrow condition such as myelodysplastic syndrome. Older adults also have worse genetics driving their leukemia, which makes the leukemia cells more resistant to chemotherapy. And the leukemia cells may even have drug efflux pumps that extrude chemotherapy that tries to enter the cell. Finally, older adults are more likely to have comorbidities that make their ability to tolerate chemotherapy much lower than for younger adults.

In someone who is newly diagnosed with AML, what initial options are they routinely given?

For someone who is older, we divide those options into three main categories.

The first is to take intensive chemotherapy, which requires a 4-6 week hospitalization and has a chance of getting somebody who is older into a remission of approximately 50% to 60%. But this also carries with it significant treatment-related mortality that may be as high as 10% to 20%. So, I have to look my older patients in the eyes when I talk about intensive chemotherapy and say, "There is a 1 in 10 or 1 in 5 chance that you might not make it out of the hospital alive."

The second prong is lower-dose therapy. While the more-intensive therapy requiring hospitalization does have a low, but real, chance of curing that person, less-intensive therapy is not curative. Our best hope with less-intensive therapy is that our patients enter a remission and live longer. With less-intensive therapy, the chance that someone will go into remission is probably around 20%, but again it is not curative. The flip side to that is that it improves a person's immediate quality of life, because they're not in the hospital for 4 to 6 weeks.

The final prong is to discuss palliative care or hospice upfront. We designed these guidelines to be focused on a patient's goals of therapy and to constantly revisit those goals to make sure that the treatment options we are offering are aligning with them.

The panel's first recommendation is to offer antileukemic therapy over best supportive care in patients who are appropriate candidates. Can you provide some context for this recommendation?

Doesn't that strike you as funny that we even have to make a recommendation about getting chemotherapy? Some database studies conducted over the past two decades show that, as recently as 15 years ago, only one third of patients who were over the age of 65 received any type of chemotherapy for AML. More recently, as we have had a few more drugs available that allow us to use lower-dose approaches, that number has crept up to probably about 50%. We still have half the patients offered no therapy at all. So, we felt that we had to deliberately make a recommendation saying that, if it aligns with a patient's goals, he or she should be offered chemotherapy.

The second recommendation is that patients considered candidates for intensive antileukemic therapy should receive it over less-intensive antileukemic therapy. How did you get to that recommendation?

There is a debate in our field about whether older adults should be offered intensive inpatient chemotherapy at all or whether we should be treating all of them with less-intensive therapy. There are not a huge amount of high-quality studies out there to answer some of these questions, in particular whether intensive chemotherapy should be recommended over less-intensive therapy. But with the available evidence, what we believe is that patients live longer if they are offered intensive antileukemic chemotherapy. So, again, if it aligns with a patient's goals, we support that patient receiving more-intensive therapy in the hospital.

What does the panel recommend for patients who achieve remission after at least a single cycle of intensive antileukemic therapy and who are not candidates for allogeneic hematopoietic stem cell transplantation?

Once again, this may seem at first blush to be an obvious recommendation. The standard treatment of someone who is younger with AML is to offer intensive inpatient chemotherapy to induce remission. This is followed by a few cycles of chemotherapy, mostly in an outpatient setting, to consolidate that remission.

What is the underlying philosophy for this approach?

Every time we give chemotherapy, we probably get about a 3 to 4 log kill of leukemia cells. Imagine when a person first presents with AML, they may have 10 billion leukemia cells in his or her body. We are reducing that 3 to 4 log with the first course of chemotherapy.

When we then look at a bone marrow biopsy, it may appear to be normal. When leukemia is at a lower level in the body, we simply can't see it using standard techniques. But that doesn't mean the leukemia is gone. For younger patients, we give another cycle of chemotherapy, then another, then another, and then even another to reduce the number of leukemia cells left over in the body until that person has a durable remission and hopefully cure.

For someone who is older, the data are less clear. While some studies have shown that if you give too much chemotherapy after the initial course, it doesn't help that much, there is a paucity of studies that show that any chemotherapy at all after the first induction course is helpful. Consequently, we have to use indirect data. Older people who are long-term survivors from their acute leukemia always seem to have gotten more than one course of chemotherapy. In other words, the initial course of chemotherapy that a patient receives in the hospital isn't enough. They should receive more than that.

What about older adults with AML considered appropriate for antileukemic therapy but not for intensive antileukemic therapy?

This again gets to the question of what are a patient's goals. It takes a very involved conversation with a person at the time of their AML diagnosis to determine whether he or she would want to pursue an aggressive approach or a less-aggressive approach. If a person wants a less-aggressive approach, and wants nothing to do with a hospital stay, then he or she is also prioritizing initial quality of life. In this recommendation, based on existing studies, we didn't have a preference for which of the available less-aggressive chemotherapies a person selects.

There's also debate about what to do in those considered appropriate for antileukemic therapy, such as hypomethylating agents (azacitidine and decitabine) or low-dose cytarabine, but not for intensive antileukemic therapy. What did the available evidence seem to indicate about this issue?

There have been a lot of studies trying to add two drugs together to see if those do better than one drug alone in patients who are older and who choose less-intensive therapy. The majority of those studies have shown no advantage to getting two drugs over one drug.

Our recommendation is that in these situations a patient gets one drug, not two, but there are a couple of caveats. One caveat is that there has been a small study showing the effectiveness of one of those low-dose chemotherapies combined with the drug glasdegib. The second caveat is that there have been results presented combining one of these low-dose chemotherapies with the drug venetoclax. One of those was a negative study, and another was a positive study showing a survival advantage to the combination vs the low-dose therapy alone. We had to couch our recommendation a little bit because we knew this other study had been presented at a conference, but it hadn't come out in final form yet. It did recently, however, and we will now revisit this recommendation.

The other complicated aspect to this is that we weren't 100% convinced that the combination of venetoclax with one of these lower-dose therapies is truly less-intensive therapy. We think it is starting to creep up toward more-intensive chemotherapy, even though it is commonly given to patients in the outpatient setting. It gets into the very complicated area of what are we defining as more-intensive therapy and less-intensive therapy.

Is there a recommended strategy for older adults with AML who achieve a response after receiving less-intensive therapy?

This is also challenging because there are no randomized studies in which patients received less-intensive therapy for a finite period of time vs receiving those therapies ad infinitum. Given the lack of data and also given a lot of anecdotal data out there about patients who stopped a certain therapy and relapsed thereafter, we recommended that patients continue the less-intensive therapy ad infinitum. So as long as they are receiving a response to that therapy, they continue on the drug.

Of course, there are also unique considerations faced by older patients who are no longer receiving antileukemic therapy, and have moved on to receiving end-of-life care or hospice care. What advice do the guidelines offer in this situation?

There are a lot of aspects of these recommendations that I think are special. The first is the focus on patient goals of care at every point in these guidelines. The second is that the guidelines follow the real disease course and a real conversation that doctors and patients have at every step of the way to help guide the decisions that have to be made in real time.

A problem we have in the United States is that once patients enter a hospice, most will not allow blood transfusions. One reason is that some say it is antithetical to their philosophy and consider it aggressive care. The second reason is that, to be completely blunt, economically it doesn't make sense for hospices to allow blood transfusions. The amount that they are reimbursed by Medicare is much lower than the cost of receiving blood in an infusion center.

We wanted to make a clear recommendation that we consider transfusions in a patient who is in a palliative care or hospice mode to be supportive and necessary, and that these should be provided to patients even if they are in hospice, and as always if consistent with a patient's goals of care.

How does a patient's age inform the discussion surrounding what intensity treatment to offer?

With younger adults, this is not as complicated a conversation. A younger person has a better chance of being cured with intensive chemotherapy and is much more likely to tolerate that intensive chemotherapy. For someone who is younger, we offer intensive chemotherapy and the chance of going into remission is higher, at 70% to 80%. The chance of dying is lower, usually less than 5%. It is an easy decision to make.

For an older adult, the riskbenefit ratio shifts and it becomes a more complicated option. Less-intensive therapy or best supportive care or hospice become viable.

Are there other factors confounding the treatment decision-making process in older adults with AML that practitioners should consider?

Someone who is older is making a different decision than I would. I have school-aged children and believe that my job as a parent is to successfully get them to adulthood, so I would take any treatment under the sun to make sure that happens. People who have lived a longer life than I have may have children and even grandchildren who are adults, and they might have different goals of care. My goals are not going to be the same as my patient's goals.

It is also harder because someone who is older may feel that he or she has lived a good life and doesn't need to go through heroic measures to try to be around as long as possible, and those goals may not align with the goals of that person's children who want their parent to be around as long as possible. One of the confounding factors in this is navigating the different goals of the different family members.

Dr Sekeres has disclosed no relevant financial relationships.

Kate O'Rourke is a freelance writer in Portland, Maine. She has covered the field of oncology for over 10 years.

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A Uniquely Patient-Focused Take on Treating AML in Older Adults - Medscape

VERIFY: Was the antibody cocktail used to treat President Trump developed using human embryonic stem cells? – CBS News 8

Social media is buzzing with the claim President Trump, who is pro-life, used an antibody cocktail developed using human embryonic stem cells.

The antibody cocktail used to treat President Donald Trump for COVID-19 is getting a lot of attention on social media.

Some users are claiming Regeneron - the company that developed the treatment - used human embryonic stem cells to create it, but is this true?

News 8 reached out to Regeneron for comment.

"This particular discovery program (regn-cov2) did not involve human stem cells or embryonic stem cells," wrote Regeneron spokesperson Alexandra Bowie in a statement.

So, where did that claim about human embryonic stem cells come from?

It appears to have developed from this statement Regeneron issued back in April 2020 regarding stem cell research:

"As is the case with many other science-focused biotechnology companies, Regeneron uses a wide variety of research tools and technologies to help discover and develop new therapeutics. stem cells are one such tool. the stem cells most commonly used at Regeneron are mouse embryonic stem cells and human blood stem cells. currently, there are limited research efforts employing human-induced pluripotent stem cell lines derived from adult human cells and human embryonic stem cells that are approved for research use by the national institutes of health and created solely through in vitro fertilization."

According to the American Association for the Advancement of Science, here's what the antibody cocktail used to treat the president is made of:

"One antibody comes from a human who had recovered from a SARS-COV-2 infection; a B cell that makes the antibody was harvested from the person's blood and the genes for the immune protein isolated and copied. The other antibody is from a mouse, which was engineered to have a human immune system, that had the spike protein injected into it."

Bowie also told News 8 the statement about stem cell research on its website reflects the company's general position on stem cell research, but does not mean human embryonic stem cells were used in creating the antibody cocktail used to treat the president.

Nevertheless, some said the company's position on using stem cells in general contradicts President Trump's pro-life stance and that of Supreme Court Nominee Amy Coney Barrett.

But the bottom line, were human embryonic stem cells used in Regeneron's antibody cocktail to treat the president? News 8 can verify the answer is no.

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VERIFY: Was the antibody cocktail used to treat President Trump developed using human embryonic stem cells? - CBS News 8

Global Stem Cell Therapy Market 2020 Industry Analysis, Size, Share, Growth, Trend and Forecast to 2025 – re:Jerusalem

MarketsandResearch.biz has published the latest market research study on Global Stem Cell Therapy Market 2020 by Company, Type and Application, Forecast to 2025 which investigates a few critical features of the market such as industry condition, division examination, market insights. The report studies the global Stem Cell Therapy market share, competition landscape, market share, growth rate, future trends, market drivers, opportunities and challenges, sales channels. The report has referenced down to earth ideas of the market in a straightforward and unassuming way in this report. The research contains the categorization of the market by top players/brands, region, type, and end-user. The report exhaustive essential investigation of current market trends, opportunities, challenges, and detailed competitive analysis of the industry players in the market.

The research report has comprehensively included numbers and figures with the help of graphical and pictorial representation which embodies more clarity on the global Stem Cell Therapy market. Then the report delivers key information about market players such as company overview, total revenue (financials), market potential, global presence, as well as market share, prices, production sites and facilities, products offered, and strategies adopted by them. Market status and outlook of global and major regions, from angles of players, countries, product types, and end industries have been analyzed.

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Key strategic manufacturers included in this report: Osiris Therapeutics, Molmed, JCR Pharmaceutical, NuVasive, Anterogen, Chiesi Pharmaceuticals, Medi-post, Pharmicell, Takeda (TiGenix)

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Key market vendors have been predicted to obtain the latest opportunities as there has been an increased emphasis on spending more on the work of research and development by many of the manufacturing companies. Also, many of the market contenders are forecasted to make a foray into the emerging economies to find new opportunities. The global Stem Cell Therapy market has gone through rapid business transformation by good customer relationships, drastic and competitive growth, significant changes within the market, and technological advancement in this market.

Geographically, this report is segmented into several key countries, with market size, growth rate, import and export of in these countries from 2015 to 2020, which covering: North America (United States, Canada and Mexico), Europe (Germany, France, United Kingdom, Russia and Italy), Asia-Pacific (China, Japan, Korea, India, Southeast Asia and Australia), South America (Brazil, Argentina), Middle East & Africa (Saudi Arabia, UAE, Egypt and South Africa)

The market can be segmented into product types as: Autologous, Allogeneic

The market can be segmented into applications as: Musculoskeletal Disorder, Wounds & Injuries, Cornea, Cardiovascular Diseases, Others

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Global Stem Cell Therapy Market 2020 Industry Analysis, Size, Share, Growth, Trend and Forecast to 2025 - re:Jerusalem

Taking Gene Editing to the Brain, the Immune System, and More – Tufts Now

One of the most remarkable recent advances in biomedical research has been the development of highly targeted gene-editing methods such as CRISPR that can add, remove, or change a gene within a cell with great precision. The method is already being tested or used for the treatment of patients with sickle cell anemia and cancers such as multiple myeloma and liposarcoma, and today, its creators Emmanuelle Charpentier and Jennifer Doudna received the Nobel Prize in chemistry.

While gene editing is remarkably precise in finding and altering genes, there is still no way to target treatment to specific locations in the body. The treatments tested so far involve removing blood stem cells or immune system T cells from the body to modify them, and then infusing them back into a patient to repopulate the bloodstream or reconstitute an immune responsean expensive and time-consuming process.

Building on the accomplishments of Charpentier and Doudna, Tufts researchers have for the first time devised a way to directly deliver gene-editing packages efficiently across the blood brain barrier and into specific regions of the brain, into immune system cells, or to specific tissues and organs in mouse models. These applications could open up an entirely new line of strategy in the treatment of neurological conditions, as well as cancer, infectious disease, and autoimmune diseases.

A team of Tufts biomedical engineers, led by associate professor Qiaobing Xu, sought to find a way to package the gene editing kit so it could be injected to do its work inside the body on targeted cells, rather than in a lab.

They used lipid nanoparticles (LNPs)tiny bubbles of lipid molecules that can envelop the editing enzymes and carry them to specific cells, tissues, or organs. Lipids are molecules that include a long carbon tail, which helps give them an oily consistency, and a hydrophilic head, which is attracted to a watery environment.

There is also typically a nitrogen, sulfur, or oxygen-based link between the head and tail. The lipids arrange themselves around the bubble nanoparticles with the heads facing outside and the tails facing inward toward the center.

Xus team was able to modify the surface of these LNPs so they can eventually stick to certain cell types, fuse with their membranes, and release the gene-editing enzymes into the cells to do their work.

Making a targeted LNP takes some chemical crafting.

By creating a mix of different heads, tails, and linkers, the researchers can screen first in the laba wide variety of candidates for their ability to form LNPs that target specific cells. The best candidates can then be tested in mouse models, and further modified chemically to optimize targeting and delivery of the gene-editing enzymes to the same cells in the mouse.

We created a method around tailoring the delivery package for a wide range of potential therapeutics, including gene editing, said Xu. The methods draw upon combinatorial chemistry used by the pharmaceutical industry for designing the drugs themselves, but instead we are applying the approach to designing the components of the delivery vehicle.

In an ingenious bit of chemical modeling, Xu and his team used a neurotransmitter at the head of some lipids to assist the particles in crossing the blood-brain barrier, which would otherwise be impermeable to molecule assemblies as large as an LNP.

The ability to safely and efficiently deliver drugs across the barrier and into the brain has been a long-standing challenge in medicine. In a first, Xus lab delivered an entire complex of messenger RNAs and enzymes making up the CRISPR kit into targeted areas of the brain in a living animal.

Some slight modifications to the lipid linkers and tails helped create LNPs that could deliver into the brain the small molecule antifungal drug amphotericin B (for treatment of meningitis) and a DNA fragment that binds to and shuts down the gene producing the tau protein linked to Alzheimers disease.

More recently, Xu and his team have created LNPs to deliver gene-editing packages into T cells in mice. T cells can help in the production of antibodies, destroy infected cells before viruses can replicate and spread, and regulate and suppress other cells of the immune system.

The LNPs they created fuse with T cells in the spleen or liverwhere they typically resideto deliver the gene-editing contents, which can then alter the molecular make-up and behavior of the T cell. Its a first step in the process of not just training the immune system, as one might do with a vaccine, but actually engineering it to fight disease better.

Xus approach to editing T cell genomes is much more targeted, efficient, and likely to be safer than methods tried so far using viruses to modify their genome.

By targeting T cells, we can tap into a branch of the immune system that has tremendous versatility in fighting off infections, protecting against cancer, and modulating inflammation and autoimmunity, said Xu.

Xu and his team explored further the mechanism by which LNPs might find their way to their targets in the body. In experiments aimed at cells in the lungs, they found that the nanoparticles picked up specific proteins in the bloodstream after injection.

The proteins, now incorporated into the surface of the LNPs, became the main component that helped the LNPs to latch on to their target. This information could help improve the design of future delivery particles.

While these results have been demonstrated in mice, Xu cautioned that more studies and clinical trials will be needed to determine the efficacy and safety of the delivery method in humans.

Mike Silver can be reached at mike.silver@tufts.edu.

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Taking Gene Editing to the Brain, the Immune System, and More - Tufts Now

Citius Pharmaceuticals Signs an Exclusive Worldwide Licensing Agreement with Novellus Therapeutics for Unique iMSC-Therapy for Acute Inflammatory…

CRANFORD, N.J., Oct. 7, 2020 /PRNewswire/ -- Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a specialty pharmaceutical company developing and commercializing critical care drug products, announced that it has signed an exclusive agreement with Novellus Therapeutics Limited ("Novellus") to license iPSC-derived mesenchymal stem cells (iMSCs), and has created a new subsidiary, NoveCite, that will be focused on developing cellular therapies.

NoveCite has a worldwide exclusive license from Novellus, an engineered cellular medicines company, to develop and commercialize NoveCite mesenchymal stem cells ("NC-iMSCs") to treat acute respiratory conditions with a near term focus on Acute Respiratory Distress Syndrome ("ARDS") associated with COVID-19. Several cell therapy companies using donor-derived MSC therapies in treating ARDS have demonstrated that MSCs reduce inflammation, enhance clearance of pathogens and stimulate tissue repair in the lungs. Almost all these positive results are from early clinical trials or under the emergency authorization program.

NC-iMSCs are the next generation mesenchymal stem cell therapy. They are believed to be differentiated and superior to donor-derived MSCs. Human donor-derived MSCs are sourced from human bone marrow, adipose tissue, placenta, umbilical tissue, etc. and have significant challenges (e.g., variable donor and tissue sources, limited supply, low potency, inefficient and expensive manufacturing). iMSCs overcome these challenges because they:

Globally, there are 3 million cases of ARDS every year out of which approximately 200,000 cases are in the United States. The COVID-19 pandemic has added significantly to the number of ARDS cases. Once the COVID patients advance to ARDS, they are put on mechanical ventilators. Death rate among patients on ventilators can be as high as 50% depending on associated co-morbidities. There are no approved treatments for ARDS, and the current standard of care only attempts to provide symptomatic relief.

"NoveCite iMSCs have the potential to be a breakthrough in the field of cellular therapy for acute respiratory conditions because of the high potency seen in Novellus' pre-clinical studies, and because iMSCs are iPSC-derived, and therefore overcome the manufacturing challenges associated with donor derived cells," said Myron Holubiak, Chief Executive Officer of Citius.

"We are excited to be part of this effort because of the promise to save lives and reduce long term sequelae in patients with devastating respiratory diseases such as ARDS caused by COVID-19," said Dr. Matthew Angel, Chief Science Officer of Novellus. "Our iMSC technology has multimodal immunomodulatory mechanisms of action that make it potentially promising therapy to treat acute respiratory diseases."

About Citius Pharmaceuticals, Inc.

Citius is a late-stage specialty pharmaceutical company dedicated to the development and commercialization of critical care products, with a focus on anti-infectives and cancer care. For more information, please visit http://www.citiuspharma.com.

About Novellus, Therapeutics, Limited

Novellus is a pre-clinical stage biotechnology company developing engineered cellular medicines using its patented non-immunogenic mRNA high specificity gene editing, mutation-free & footprint-free cell reprogramming and serum insensitive mRNA lipid delivery technologies. Novellus is privately held and is headquartered in Cambridge, MA. For more information, please visit http://www.novellus-inc.com.

About NoveCite iMSC (NC-iMSC)

NoveCite's mesenchymal stem cell therapy product is derived from a human induced pluripotent stem cell (iPSC) line generated using a proprietary mRNA-based (non-viral) reprogramming process. The NC-iMSCs produced from this clonal technique are differentiated from human donor-derived MSCs (bone marrow, placenta, umbilical cord, adipose tissue, or dental pulp) by providing genetic homogeneity. In in-vitro studies, NC-iMSCs exhibit superior potency and high cell viability. NC-iMSCs secrete immunomodulatory proteins that may reduce or prevent pulmonary symptoms associated with acute respiratory distress syndrome (ARDS) in patients with COVID-19. NC-iMSC is an allogeneic (unrelated donor) mesenchymal stem-cell product manufactured by expanding material from a master cell bank.

First generation (human donor-derived) MSCs are isolated from donated tissue followed by "culture expansion". Since only a relatively small number of cells are isolated from each donation, first generation MSCs are increased by growing the cells in culture. Unfortunately, these type of MSCs start to lose potency, and ultimately become senescent. Each donation produces a limited number of MSCs, so a continuous supply of new donors is needed to produce commercial scale. The number and quality of MSCs that can be isolated from different donors can vary substantially.

About Acute Respiratory Distress Syndrome (ARDS)

ARDS is an inflammatory process leading to build-up of fluid in the lungs and respiratory failure. It can occur due to infection, trauma and inhalation of noxious substances. ARDS accounts for approximately 10% of all ICU admissions and almost 25% of patients requiring mechanical ventilation. Survivors of ARDS are often left with severe long-term illness and disability. ARDS is a frequent complication of patients with COVID-19. ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). Symptoms of ARDS include shortness of breath, rapid breathing and heart rate, chest pain (particularly while inhaling), and bluish skin coloration. Among those who survive ARDS, a decreased quality of life is relatively common.

Safe Harbor

This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are: the risks associated with developing the NoveCite technology as a treatment for ARDS; risks associated with developing any of our product candidates, including any licensed from Novellus, Inc., including that preclinical results may not be predictive of clinical results and our ability to file an IND for such candidates; our need for substantial additional funds; the estimated markets for our product candidates, including those for ARDS, and the acceptance thereof by any market; risks relating to the results of research and development activities; uncertainties relating to preclinical and clinical testing; the early stage of products under development, including the NoveCite technology; our ability to obtain, perform under and maintain licensing, financing and strategic agreements and relationships; our ability to attract, integrate, and retain key personnel; risks related to our growth strategy; our ability to identify, acquire, close and integrate product candidates and companies successfully and on a timely basis; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Contact: Andrew Scott Vice President, Corporate Development (O) 908-967-6677 x105 (M) 646-522-8410 ascott@citiuspharma.com

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Company Codes: NASDAQ-SMALL:CTXR

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