Archive for December, 2020

Novartis already knew that adding Kisqali to endocrine therapy can help premenopausal patients with HR-positive, HER2-negative advanced breast cancer live longer. Now, it knows exactly how long.

Kisqali plus endocrine therapy helped pre- and perimenopausal women with HR+/HER2- disease live a median 58.7 months, according to phase 3 data presented at the San Antonio Breast Cancer Symposium's (SABCS') virtual annual meeting. Thats compared with 48 months forendocrine therapy alone, translating to a 24% reduction in the risk of death for the Kisqali regimen.

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Jeff Legos, Ph.D., Novartis head of oncology drug development, called Kisqalis new survival showing very impressive given that these patients historically survived for around three years after treatment. Patients in the control arm of the Monaleesa-7 trial appeared to live longer because some went on to receive Kisqali afteran initial survival readout, which showed a 29% reduction in the risk of death.

The Kisqali regimen also extended the time period before patients need follow-up chemotherapy by about 31%. Patients on the Kisqali combo lived a median 50.9 months before their first post-treatment chemo, while the time was 36.8 months for endocrine therapy alone.

The survival benefit was similar in a subgroup of patients who took a nonsteroidal aromatase inhibitor (NSAI) as part of their endocrine therapy. The death risk reduction in those patients was 20%, as the Kisqali group also lived a median 58.7 months, versus 47.7 months for the control arm.

RELATED:ASCO: Novartis' Kisqali posts first-in-class survival win in younger women

Thats the most relevant data for Kisqali in this patient population,given that its only approved by the FDA in combination with an NSAI. The Monaleesa-7 study also tested tamoxifen as an endocrine option, but, in those patients, researchers identified ahigher-than-expected increase in an abnormal heart rhythm called QT prolongation.

Novartis has now reported statistically significant life extension benefits for Kisqali in premenopausal women in the Monaleesa-7 trial and in postmenopausal women in the Monaleesa-3 study.The Monaleesa-2 program testing Kisqali in combination with the endocrine therapy letrozole in previously untreated patients is expected to have overall survival data in the second half of 2021.

The current Monaleesa-7 study was carried out in patients who hadnt been previously treated witha CDK4/6 inhibitor or endocrine therapy, but it did allowprevious treatment with chemotherapy.

Biomarker victory over Ibrance

In a cherry on top of Kisqalis 2020 SABCS data cake, Novartis unveiled a pooled analysis of the three trials showing the CDK4/6 inhibitor reduced the risk of disease progression or death in three of the four main subtypes of breast cancer.

In patients with the more traditional Luminal A and Luminal B subtypes, where Legos said patients have done reasonably OK with solo endocrine therapy, adding Kisqali significantly slashed the risk of disease progression or death by 37% and 48%, respectively, across the three trials.

The best news for Kisqali, though, according to Legos, came fromthe HER2-enriched subtype, which makes up about 15% of the HR+/HER2- breast cancer population. This subgroup traditionally had not done very well on endocrine therapy alone and hence it can be sort of deemed as a poor prognostic factor, Legos explained.

But in this group, the Kisqali-endocrine pairing cut the risk of disease progression or death by 61%.

RELATED:ESMO: Lilly's Verzenio pressures Pfizer with practice-changing win in early breast cancer

The showing in this subtype is important because its the first time a CDK4/6 inhibitor combo topped endocrine therapy alonein these women, Legos said. Three years ago at the SABCS event, a retrospective analysis of the Paloma-2 trial found Pfizers market-leading CDK4/6 inhibitor, Ibrance, didnt benefit the HER2-enriched subtype, he pointed out.

I think this just addsto the growing body of evidence that these mixed results that were seeing in both the metastatic setting, as well as in the adjuvant setting, may suggest that not all of the CDK4/6 inhibitors are equal, Legos said in an interview ahead of the data presentation.

Indeed, Ibrance has repeatedly failed in several HR+/HER2- breast cancer trials. The most famous is the Paloma-3 trial, which showed adding Ibrance to endocrine therapy in metastatic patients didnt significantly beat endocrine therapy at extending patients lives.

RELATED:Pfizer's Ibrance kisses early breast cancer hopes goodbye with 2nd study failure

And, in the postsurgery setting known as adjuvant treatment, Ibrance recently failed to lengthen the time early breast cancer patients could live without invasive disease returning. It didnt deliver a benefit in a wider patient group or in a high-risk subgroup.

Meanwhile, updated data from the phase 3 monarchE trial presented at this years SABCS showed the adjuvant pairing of Eli Lillys rival CDK4/6 inhibitor Verzenio and endocrine therapy reduced the risk of invasive disease after surgery by 28.7% in high-risk patients with an extended follow-up of 19 months.

CDK4 versus CDK6

Novartis has been attributing Kisqalis better efficacyas compared to Ibrancesto its drugs higher inhibition of CDK4 over CDK6. While CDK4 is more widely expressed in breast cancer cells, CDK6 is found more in the bone marrow; plus, CDK4 plays a greater role in cell proliferation and growth, Legos explained. Verzenio also inhibits CDK4 to a higher degree.

Kisqali isnt omnipotent, though. The Novartis drug didnt show a tumor progression improvement in the basal-like subtype. Legos said this represents a small group of patients whose tumors resemble triple-negative breast cancer. These patients constitute an average 3% of participants across the three Monaleesa trials, which Legos said is reflective of the real-world makeup.

Novartis is running a separate trial called Natalee, hoping to show that Kisqali on top of endocrine therapy works as an adjuvant treatment for both intermediate and high-risk patients. Data from that trial areexpected in 2022.

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SABCS: Novartis touts Kisqali's 5-year breast cancer survival, advantage over Pfizer's Ibrance - FiercePharma

HAMBURG, GERMANY / ACCESSWIRE / December 9, 2020 / Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and the life science company Sartorius announced today that they have entered into a partnership with the recently established Curexsys GmbH, a Goettingen, Germany-based technology leader specialising in the emerging field of therapeutic exosomes.

Curexsys delivers a proprietary isolation technology for exosomes based on a traceless immune-affinity process. This process is different from commonly used antibody-based processes and enables the company to overcome a key hurdle in exosome preparation, i.e. remaining antibodies in the final preparation. Curexsys is founded by Herbert Stadler, a serial biotech entrepreneur, and Jens Gruber, a former group leader of Medical RNA Biology who is going to lead Curexsys as Chief Scientific Officer.

Under the terms of the agreement, Evotec and Curexsys will collaborate with the production of Human Mesenchymal Stem Cells ("MSCs"), which serve as a source for exosomes. These are small vesicles that are naturally released from a cell. They contain proteins, nucleic acids and metabolites, which carry information from secreting to receiving cells. Exosomes have immunomodulatory and anti-inflammatory effects, which makes them a promising novel approach for innovative regenerative therapies, as therapeutics in age-related conditions, but also for diagnostic purposes. Curexsys aims to develop targeted approaches for a variety of diseases, initially focusing on Sicca Syndrome, commonly known as "dry eye", an inflammatory condition affecting 14% to 17% of the adult population for whom there is currently no effective treatment available.

The collaboration combines Evotec's industry-leading induced Pluripotent Stem Cell ("iPSC") platform with Curexsys' proprietary technology to selectively isolate exosomes. Sartorius will support Curexsys to set up a GMP-compliant and scalable manufacturing platform.

Furthermore, Evotec and Sartorius have formed a consortium to jointly invest in Curexsys' 8.2 m seed financing round with Evotec acquiring an equity stake of approx. 37% in Curexsys and Sartorius of approx. 21%.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "Therapeutic exosomes hold significant promise for regenerative medicine and beyond. Steadily increasing evidence suggests that exosomes derived from stem cells can aid tissue repair and engineering vesicles could carry drugs to diseased tissues. These efforts have been held back by a dearth of standardised methods to isolate and study vesicles. Combining Evotec's industrial-grade iPSC and PanOmics platforms with Curexsys' proprietary exosome isolation technology and Sartorius' ability to translate these into a fully GMP-compliant process is a unique opportunity to build the leading exosome company in the industry."

Dr Ren Faber, Head of Sartorius' Bioprocess Solutions Division, said: "With our integrated portfolio of manufacturing solutions Sartorius is the 'go-to' partner for developers of such new modalities when it comes to implementing GMP-compliant, flexible production processes. We are very much looking forward to contributing our proven and scalable technology platform to Curexsys process and help them achieve their next milestones faster."

Dr Jens Gruber, Chief Scientific Officer of Curexsys, added: "We are very happy that we were able to form such a consortium with industry leaders in their field. This unique constellation gives Curexsys an optimal starting position to advance our technologies for highly specific isolation of exosomes and to rapidly approach therapeutic applications."

About Exosomes and CurexsysExosomes are extracellular, nanoscale vesicles that are actively secreted from cells to transfer information to neighbouring cells and distant tissues. Exosomes carry information of secreting to receiving cells utilising proteins, nucleic acids and metabolites. MSC-derived exosomes function as paracrine mediators that limit inflammation, reprogram immune cells, and activate endogenous repair pathways, recapitulating to a large extent the therapeutic effects of parental MSCs. Exosomes hold potential as diagnostics, as therapeutics and cosmeceuticals. More than 100 clinical trials involving exosomes are currently ongoing, demonstrating their broad therapeutic potential.

Curexsys is a Goettingen, Germany-based start-up company founded by molecular biologist Dr Jens Gruber and the biochemist and serial entrepreneur Dr Herbert Stadler. With a scalable and semi-automated proprietary system for traceless immune-affinity cell sorting, Curexsys aims to become the leading supplier for clinical grade exosomes in regenerative medicine and anti-aging therapies.

About Evotec and iPSCInduced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

Evotec has built an industrialised iPSC infrastructure that represents one of the largest and most sophisticated iPSC platforms in the industry. Evotec's iPSC platform has been developed over the last years with the goal to industrialise iPSC-based drug screening in terms of throughput, reproducibility and robustness to reach the highest industrial standards, and to use iPSC-based cells in cell therapy approaches via the Company's proprietary EVOcells platform.

ABOUT SARTORIUSThe Sartorius Group is a leading international partner of life science research and the biopharmaceutical industry. With innovative laboratory instruments and consumables, the Group's Lab Products & Services Division concentrates on serving the needs of laboratories performing research and quality control at pharma and biopharma companies and those of academic research institutes. The Bioprocess Solutions Division with its broad product portfolio focusing on single-use solutions helps customers to manufacture biotech medications and vaccines safely and efficiently. The Group has been annually growing by double digits on average and has been regularly expanding its portfolio by acquisitions of complementary technologies. In fiscal 2019, the company earned sales revenue of some 1.83 billion euros. At the end of 2019, more than 9,000 people were employed at the Group's approximately 60 manufacturing and sales sites, serving customers around the globe.

SARTORIUS CONTACTPetra KirchhoffHead of Corporate Communications and Investor Relations+49 (0)551.308.3684 petra.kirchhoff@sartorius.comwww.sartorius.com

ABOUT EVOTEC SEEvotec is a drug discovery alliance and development partnership company focused on rapidly progressing innovative product approaches with leading pharmaceutical and biotechnology companies, academics, patient advocacy groups and venture capitalists. We operate worldwide and our more than 3,400 employees provide the highest quality stand-alone and integrated drug discovery and development solutions. We cover all activities from target-to-clinic to meet the industry's need for innovation and efficiency in drug discovery and development (EVT Execute). The Company has established a unique position by assembling top-class scientific experts and integrating state-of-the-art technologies as well as substantial experience and expertise in key therapeutic areas including neuronal diseases, diabetes and complications of diabetes, pain and inflammation, oncology, infectious diseases, respiratory diseases, fibrosis, rare diseases and women's health. On this basis, Evotec has built a broad and deep pipeline of more than 100 co-owned product opportunities at clinical, pre-clinical and discovery stages (EVT Innovate). Evotec has established multiple long-term alliances with partners including Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CHDI, Novartis, Novo Nordisk, Pfizer, Sanofi, Takeda, UCB and others. For additional information please go to http://www.evotec.com and follow us on Twitter @Evotec.

FORWARD LOOKING STATEMENTSInformation set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

SOURCE: Evotec AG via EQS Newswire

View source version on accesswire.com:https://www.accesswire.com/620112/Evotec-and-Sartorius-Partner-with-Start-Up-Curexsys-on-IPSC-Based-Therapeutic-Exosome-Approach

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Evotec and Sartorius Partner with Start-Up Curexsys on IPSC-Based Therapeutic Exosome Approach - BioSpace

After 15 years of unrelenting work, a team of scientists from Gladstone Institutes has now discovered a potential drug candidate for heart valve disease that works in both human cells and animals and is ready to move toward a clinical trial. Their findings were just published in the journal Science.

"The disease is often diagnosed at an early stage and calcification of the heart valves worsens over the patient's lifetime as they age," says Gladstone President and Director of the Roddenberry Stem Cell Center Deepak Srivastava, MD,who led the study. "If we could intervene early in life with an effective drug, we could potentially prevent the disease from occurring. By simply slowing the progression and shifting the age of people who require interventions by 5 or 10 years, we could avoid tens of thousands of surgical valve replacements every year."

This also applies to the millions of Americansabout one to two percent of the populationwith a congenital anomaly called bicuspid aortic valve, in which the aortic valve only has two leaflets instead of the normal three. While some people may not even know they have this common heart anomaly, many will be diagnosed as early as their forties.

"We can detect this valve anomaly through an ultrasound," explains Srivastava, who is also a pediatric cardiologist and a professor in the Department of Pediatrics at UC San Francisco (UCSF). "About a third of patients with bicuspid aortic valve, which is a very large number, will develop enough calcification to require an intervention."

Srivastava's research into heart valve disease started in 2005, when he treated a family in Texas who had this type of early-onset calcification. All these years later, thanks to the family's donated cells, his team has finally found a solution to help them and so many others.

A Holistic Approach in the Hunt for a Therapy

Members of the family treated by Srivastava had disease that crossed five generations, enabling the team to identify the causea mutation in one copy of the gene NOTCH1. Mutations in this gene cause calcific aortic valve disease in approximately four percent of patients and can also cause thickening of valves that trigger problems in newborns. In the other 96 percent of cases, the disease occurs sporadically.

"The NOTCH1 mutation provided a foothold for us to figure out what goes wrong in this common disease, but most people won't have that mutation," says Srivastava. "However, we found that the process that leads to the calcification of the valve is mostly the same whether individuals have the mutation or not. The valve cells get confused and start thinking they're bone cells, so they start laying down calcium and that leads to hardening and narrowing of the valves."

In the hunt for a treatment, the group of scientists chose a novel, holistic approach rather than simply focusing on a single target, such as the NOTCH1 gene.

"Our goal was to develop a new framework to discover therapeutics for human disease," says Christina V. Theodoris, MD, PhD, lead author of the study who is now completing her residency in pediatric genetics at Boston Children's Hospital. "We wanted to find promising therapies that could treat the disease at its core, as opposed to just treating some specific symptoms or peripheral aspects of the disease."

When Theodoris first joined Srivastava's lab at Gladstone, she was a graduate student at UCSF. At the time, they knew the NOTCH1 gene mutation caused valve disease, but they didn't have the tools to study the problem further, largely because it was very difficult to obtain valve cells from patients.

"My first project was to convert the cells from the patient families into induced pluripotent stem (iPS) cells, which have the potential of becoming any cell in the body, and turn them into cells that line the valve, allowing us to understand why the disease occurs," says Theodoris. "My second project was to make a mouse model of calcific aortic valve disease. Only then could we start using these models to identify a therapy."

One Drug Candidate Rises to the Top

For this latest study, the scientists searched for drug-like molecules that could correct the overall network that goes awry in heart valve disease and leads to calcification. To do so, they first had to determine the network of genes that are turned on or off in diseased cells.

Then, they used an artificial intelligence method, training a machine learning program to detect whether a cell was healthy or sick based on this network of genes. They subsequently treated diseased human cells with nearly 1,600 molecules to see if any drugs shifted the network in the cells enough that the machine learning program would reclassify them as healthy. The researchers identified a few molecules that could correct diseased cells back to the normal state.

"Our first screen was done with cells that have the NOTCH1 mutation, but we didn't know if the drugs would work on the other 96 percent of patients with the disease," says Srivastava.

Fortunately, Anna Malashicheva, PhD, from the Russian Academy of Sciences, had collected valve cells from over 20 patients at the time of surgical replacement, and Srivastava struck up a fruitful collaboration with her group to do a "clinical trial in a dish."

"We tested the promising molecules on cells from these 20 patients with aortic valve calcification without known genetic causes," Srivastava adds. "Remarkably, the molecule that seemed most effective in the initial study was able to restore the network in these patients' cells as well."

Once they had identified a promising candidate in cells in a dish for both NOTCH1 and sporadic cases of calcific aortic valve disease, Srivastava and his team did a "pre-clinical trial" in a mouse model of the disease. They wanted to determine whether the drug-like molecule would actually work in a whole, living organ.

The scientists confirmed that the therapeutic candidate could successfully prevent and treat aortic valve disease. In young mice who had not yet developed the disease, the therapy prevented the calcification of the valve. And in mice that already had the disease, the therapy actually halted the disease and, in some cases, led to reversal of the disease. This finding is especially important since most patients aren't diagnosed until calcification has already begun.

"Our strategy to identify gene networkcorrecting therapies that treat the core disease mechanism may represent a compelling path for drug discovery in a range of other human diseases," says Theodoris. "Many therapeutics found in the lab don't translate well to humans or focus only on a specific symptom. We hope our approach can offer a new direction that could increase the likelihood of candidate therapies being effective in patients."

The researchers' strategy relied heavily on technological advancements, including human iPS cells, gene editing, targeted RNA sequencing, network analysis, and machine learning.

"Our study is a really good example of how modern technologies are facilitating the kinds of discoveries that are possible today, but weren't not so long ago," says Srivastava. "Using human iPS cells and gene editing allowed us to create a large number of cells that are relevant to the disease process, while powerful machine learning algorithms helped us identify, in a non-biased fashion, the important genes for distinguishing between healthy and diseased cells."

"By using all the knowledge we gathered over a decade and a half, combined with the latest tools, we were able to find a drug candidate that can be taken to clinical trials," he adds. "Our ultimate goal is always to help patients, so the whole team is very pleased that we found a therapy that could truly improve lives."

About the Research Project

The paper, "Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease,"was published online by Science on December 10, 2020.

Other authors include Ping Zhou, Lei Liu, Yu Zhang, Tomohiro Nishino, Yu Huang, Sanjeev S. Ranade, Casey A. Gifford, Sheng Ding from Gladstone; Aleksandra Kostina from the Russian Academy of Sciences; and Vladimir Uspensky from the Almazov Federal Medical Research Centre in Russia.

The work was funded by the California Institute of Regenerative Medicine; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources. Gladstone researchers also received support from the Winslow Family, the L.K. Whittier Foundation, The Roddenberry Foundation, the Younger Family Fund, the American Heart Association, several programs and fellowships at UCSF, residency programs from Boston Children's Hospital and the Harvard Medical School, the Uehara Memorial Foundation, and a Howard Hughes Medical Institute Fellowship of the Damon Runyon Cancer Research Foundation.

About Gladstone Institutes

To ensure our work does the greatest good, Gladstone Institutes focuses on conditions with profound medical, economic, and social impactunsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease.

Media Contact: Julie Langelier | Assistant Director, Communications | [emailprotected] | 415.734.5000

SOURCE Gladstone Institutes

https://gladstone.org

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A Potential Therapy for One of the Leading Causes of Heart Disease - PRNewswire

A new clinical trial offers the most compelling evidence to date that a donor stem cell transplant can improve survival rates for older patients with higher-risk myelodysplastic syndrome (MDS), Dana-Farber Cancer Institute investigators report at the virtual 62nd American Society of Hematology (ASH) Annual Meeting.

Despite being the only current cure for MDS and widely used for younger patients, transplant generally hasnt been offered to older patients because it has not been proven beneficial in that population. The new trial, conducted by the Blood and Marrow Transplant Clinical Trials Network, is likely to change that, according to study leaders. Involving 384 patients at 34 medical centers across the U.S., the trial found that transplantation of hematopoietic stem cells from compatible donors nearly doubled the survival rate of patients age 50-75.

Transplantation has been underutilized, historically, in this patient group, said study senior author Corey Cutler, MD, MPH, FRCPC, of Dana-Farber. Based on our findings all patients should at least be referred to a transplant center so that those who are eligible and have a suitable donor can undergo transplant and have better survival. It is important to refer these patients early so the transplant center can work on finding an optimal donor right from the get-go.

MDS encompasses a group of disorders in which blood-forming cells in the bone marrow become abnormal, resulting in the production of defective blood cells. In about one in three patients, MDS can progress to acute myeloid leukemia, a rapidly growing cancer of bone marrow cells.

Allogeneic hematopoietic stem cell transplantation replaces a patients abnormal blood-forming stem cells with healthy ones from a compatible donor. Because the procedure hadnt been proven to be helpful for older patients, it hasnt been covered by Medicare for people over age 65 unless done as part of an approved study. Medicare approved the design of the trial and is expected to consider the findings when determining future payment policies.

Participants in the new trial were referred to transplant centers, which searched for suitable stem cell donors. The 260 patients who were matched with a donor within 90 days were assigned to receive a stem cell transplant; the other 124 patients received standard supportive care.

Roughly three years after enrolling in the trial, 47.9% of those slated for transplant were alive, compared to 26.6% of those for whom no donor had been found at the 90-day mark. Survival without a recurrence of leukemia was also higher in those assigned to receive a transplant (35.8%) than in those who were not (20.6%). The researchers observed no significant differences among subgroups and no differences in quality of life between the two study arms.

Cutlerpresented findings on this study at the Whats on the Horizon: Practice-Changing Clinical Trials press briefing on Friday, Dec. 4 at 12:30 p.m. EST. Further details were presented during Session 732, Abstract 75, on Saturday, Dec. 5 at 10:30 a.m. EST.

Cutlers disclosures include a consulting or advisory role for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Complete details on Dana-Farbers activities at ASH are available online at http://www.dana-farber.org/ash.

This press releasewas originally published on December 4, 2020, by Dana-Farber Cancer Institute. It is republished with permission.

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Donor Stem Cell Transplant Improves Survival in Older Patients with Myelodysplastic Syndrome - Cancer Health Treatment News

By Staff Reporter 7m ago

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CAPE TOWN - International cricketer JP Duminy has his sights set on raising R400 000 in conjunction with the South African Bone Marrow Registry (SABMR) the figure thats still needed this year for them to match donors with patients suffering from life-threatening blood disorders who cant afford it.

Alicia Venter, Head of Patient Services at the SABMR says for many who dont have medical aid, the costs associated with finding a donor are a barrier to getting the life-saving treatment they need.

These costs include the search for an unrelated donor match in cases where no suitably matched donors are found among family members, testing and verification, the procurement and transportation of stem cells (from anywhere in the world), as well as travel and accommodation of the donor should the collection centre be far from home. Costs related to bone marrow stem cell transplants from international donors are more than double that of local donors.

Our Patient Assistance Programme is available to patients who are unable to obtain adequate funds for the treatment or in cases where their medical aid doesnt cover donor searches, despite appeal, explains Venter.

The SABMRs Give a Little Save a Life campaign, which kicks off on 10 December is being steered by Duminy, who is a long-time ambassador for the registry.

The Covid-19 pandemic has resulted in all the SABMRs events being cancelled, which usually brings in the bulk of the funds annually for the Patient Assistance Programme.

Right now, there are two young South Africans awaiting bone marrow stem cell transplants, whose families cant afford the cost of finding a donor.

One is a 6-year-old boy from Gauteng who has been diagnosed with Acute Lymphocytic Leukaemia and the other a 19-year-old girl from the Free State who has Acute Myeloid Leukaemia.

Their only hope of survival is a stem cell transplant. By rallying together, we can raise the funds to make it a reality and give them the second chance they deserve. In my life, Ive experienced many exhilarating moments both on and off the field and wish the same for these two young patients and others who are in a similar position. If you have the means to give, even if its just R50, youll never regret it.

At any given time, there are more than 200 patients in SA that need a bone marrow transplant unfortunately, many of whom cant afford it. While its been a tough year with very little funding coming in, the SABMR managed to redirect funds from its own reserves toward the programme.

This has helped to cover some of the key costs associated with finding suitably matched unrelated donors for eight patients.

Kamiel Singh, Head of Sustainability at the SABMR says while this years Give a Little Save a Life campaign will be solely online, he hopes it will galvanise a new generation of social media-savvy fundraisers that will support the SABMRs efforts.

Social media enables people to engage with each other and healthcare in ways that were almost unimaginable a decade ago. By combining the power of social media and sporting heroes such as JP Duminy, we hope to raise enough funds to make a real difference to the lives of hundreds of patients suffering from blood disorders in the coming year, says Singh.

Donations toward the registrys Patient Assistance Programme can be made via:

https://www.backabuddy.co.za/sabmrgivealittle and http://www.sabmr.co.za where there are various payment options available.

The SABMRs Give a Little Save a Life campaign can be followed on the following social media platforms: Facebook Twitter and Instagram

@IOLSport

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JP Duminy goes to bat for the SA Bone Marrow Registry - IOL

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 - Business Wire

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, today announced clinical data from its ongoing multicenter Phase 1 clinical trial of JSP191, a first-in-class anti-CD117 monoclonal antibody, in patients with severe combined immune deficiency (SCID). The trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with SCID who are either transplant-naive or who received a prior stem cell transplant with a poor outcome.

Data from the first transplant-nave SCID patient in the Phase 1 trial, a 6-month-old infant, showed that a single dose of JSP191 administered prior to stem cell transplant was effective in establishing sustained donor chimerism followed by development of B, T and NK immune cells. No treatment-related adverse events were reported. The data were presented by primary investigator Rajni Agrawal-Hashmi, M.D., of Stanford University, at the 62nd American Society of Hematology (ASH) Annual Meeting & Exposition.

We have previously shown that JSP191 can be successfully used as a single conditioning agent in SCID patients who had failed a previous transplant, said Kevin N. Heller, M.D., Executive Vice President, Research and Development, of Jasper Therapeutics. This new data presented at ASH 2020 showing success in an infant with SCID undergoing a first transplant provides proof of concept of the safety and efficacy of the use of JSP191 as an alternative to genotoxic chemotherapies currently used to deplete stem cells prior to transplant.

Hematopoietic cell transplantation offers the only curative therapy for SCID, a severe genetic immune disorder that leaves patients without a functioning immune system. With this approach, standard-of-care chemotherapeutic conditioning regimens are given prior to transplant to reduce the number of blood stem cells in the bone marrow to make space for donor blood stem cells to engraft and cure the patient. JSP191 is designed to replace the need for chemotherapeutic conditioning agents, which are DNA-damaging and highly toxic.

Dr. Heller added, With our Phase 1 trials in SCID and hematologic disorders underway, we are planning to expand the development of JSP191 into additional indications, such as gene therapies, autoimmune diseases, Fanconis anemia and other rare disorders that can be cured by stem cell transplant.

The open-label, multicenter Phase 1 study is evaluating the safety, tolerability and efficacy of JSP191 as a conditioning agent in patients with SCID undergoing first or repeat hematopoietic cell transplantation. Up to three different doses of JSP191 are being assessed for dose-limiting toxicities. The trial is currently open for enrollment at Stanford University, the University of California, San Francisco, Memorial Sloan Kettering Cancer Center, the University of California, Los Angeles, and Cincinnati Childrens Hospital. Additional clinical trial sites in the United States will initiate enrollment in the coming weeks.

About SCID

Severe combined immune deficiency (SCID) is a group of rare disorders caused by mutations in genes involved in the development and function of infection-fighting immune cells. Infants with SCID appear healthy at birth but are highly susceptible to severe infections. The condition is fatal, usually within the first year or two of life, unless infants receive immune-restoring treatments, such as transplants of blood-forming stem cells, gene therapy or enzyme therapy.

About JSP191

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in animal models of SCID, myelodysplastic syndromes (MDS) and sickle cell disease (SCD). Treatment with JSP191 creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients.

JSP191 is currently being evaluated as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for severe combined immunodeficiency (SCID), which is potentially curable only by this type of treatment. JSP191 is also being evaluated in a Phase 1 study in patients with MDS or acute myeloid leukemia (AML) who are receiving hematopoietic cell transplant. For more information about the design of these clinical trials, visit http://www.clinicaltrials.gov (NCT02963064 and NCT04429191). Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The companys lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplant. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. For more information, please visit us at jaspertherapeutics.com.

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Jasper Therapeutics Announces Data from First Transplant-naive Patient in Phase 1 Clinical Trial of JSP191 as Conditioning Agent in Patients with SCID...

A FORMER hairdresser from Bournemouth is appealing for people to help raise money to have life-saving surgery in Mexico to get rid of her Multiple Sclerosis once and for all.

Having been admitted to Royal Bournemouth Hospital for a suspected stroke or brain tumour in March 2017, at the age of 47, Kirsten Hannibal was found to have multiple lesions on her brain and was diagnosed with CIS which later progressed to MS.

During lockdown, Kirsten has researched into different ways to stop Multiple Sclerosis dead in its tracks, one of them being Hematopoietic Stem Cell Transplantation.

Although the procedure, which involves the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, is not widely accessible in the UK, it is available in Mexico, considered a world class hub for HSCT.

However she must raise over 40,000 to cover flights to Mexico as well as the cost of the procedure.

Vicky Dixon has set up a crowdfunding page to raise money for Kirstens medical procedure.

In a statement written on her crowdfunding page, she said: Our family are joining forces to raise the money needed to send our Kirsten to Mexico for Hematopoietic Stem Cell Transplantation treatment that is not universally available on the NHS, but will hopefully give Kirsten a chance of a future; a life free of pain, disability and heart breaking challenges.

We hope that Kirsten can follow the footsteps of other British MS sufferers and go to Mexico, a world class centre for HSCT, and cheaper than the UK, at the cost of 43,500.

The first large, randomised control trial, and several meta-analyses of HSCT, have confirmed that HSCT is a very effective therapy. This is now tipping the scales for HSCT becoming a mainstream treatment for MS in Britain.

However, the treatment has to take place before the MS becomes too advanced, and as it will be years before HSCT might be offered more widely, Kirsten would by then be swallowed up by the MS and not a suitable candidate for treatment.

Kirsten is on the brink of becoming too disabled for this treatment, hence the urgency of our appeal.

Sadly, the 46-year-old is now travelling a path similar to one her family have walked before.

In 1984 her mother at the age of 32 was diagnosed with lymphoblastic leukaemia and the Echo covered the story.

Her mother underwent aggressive chemotherapy and was the receiver of a ground-breaking treatment with a bone marrow transplant.

She was the first patient to receive this treatment in the south and, whilst the treatment was deemed a success, sadly her mother died.

Lynda Smiths legacy lives on because her bravery in allowing this treatment to take place is now the lifeline to many children and adults alike who survive leukaemia.

The treatment Kirsten is looking to have is similar to her mothers treatment, except it would be her own bone marrow that would be harvested. She will then be given chemotherapy and then the day Kirsten longs for, freedom from the disease.

The new birthday she dreams of is a stem cell birthday celebrated when the bone marrow is put back into her body giving her the chance of stopping Multiple Sclerosis.

So far, Kirstens fundraising appeal has raised 4,535, just over 10 per cent of her target.

To donate, visit https://www.gofundme.com/f/multiple-sclerosis-and-an-urgent-bid-for-freedom?utm_source=customer&utm_medium=email&utm_campaign=p_cp+sharesheet.

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Bid to fund stem cell treatment in Mexico for woman with MS - Bournemouth Echo

Cell therapies involve the transfer of live cells into a patient to help treat, prevent or potentially cure diseases. One category of cell therapy focuses specifically on the use of stem cells, or cells within the body that have the potential to replace those that are lost through injury or disease. Their versatility and ability to transform allow them to replace problematic or deactivated cells with new, healthy ones is giving patients around the world a second chance at life.Stem cells are found all throughout the human bodyincluding the skin, muscle tissue and even deep inside bone marrow.

Bone marrow, the spongy substance that fills the inner cavities of our bones, is a rich source ofhematopoietic stem cells. These cells are particularly valuable for their ability to develop into all types of blood cells, including white blood cells, red blood cells and platelets. Due to their unique ability,hematopoietic cells can be used to treat certain types of cancer, such as leukemia and lymphomaand have become a staple in the field of regenerative medicine.

Bone marrow aspirate concentrate(BMAC) is a procedure that collects bone marrow from a patient's body and then concentrates it to create the optimal level of stem cells and other crucial growth factors, which can offer a variety of health benefits that traditional surgical methods simply can't offer. Stem cells and their descendants, known as progenitor cells, combined with other bone marrow cells and platelets, have the potential to restore function when injected directly into the patient's damaged tissue. The BMAC procedure is popularly used by physicians who practice orthopedic surgery, pain management and sports medicine. It has been shown torepair tissue damage, preserving function and strengthand in some cases has even beenused as an alternative for more intensive procedures such as joint and hip replacements.

Bone Marrow Aspirate Concentrate is currently being used to:

While there are many bone marrow concentrate technologies currently out on the market, there are none quite like theThermoGenesis PXPSystem. The PXPSystem is an automated, closed system designed for sterile bone marrow separation and concentration. The automated system utilizes highly sensitive sensors to reduce the amount of red blood cells (RBCs) from the initial bone marrow aspirate, providing physicians with a high-quality final product.Red blood cell contaminationis, by far, the biggest issue physicians encounter when using open, non-automated bone marrow processing systems. When high RBC contamination occurs in the bone marrow concentrate, it can impair cell function and diminish the overall effectiveness of the cell treatments. The PXPSystem is specifically designed to eliminate RBCs contamination head-on, boasting aRBC reduction of over 99 percent.

[Link]

The PXPSystem obtains bone marrow concentrates easily, consistently, and reliably, setting itself apart from any other competitors on the market today. The automated nature of the system eliminates factors created by human error and allows for increased precision and control. It gives its user the ability to harvest a precise volume of cell concentrate from the bone marrow aspirate, while producing consistently high mononuclear cells (MNCs) and CD34+ progenitor cell recoveries.

[Link][Link]

Bone marrow aspirate is collected from the patient through a minimally invasive procedure, usually done under local or general anesthesia. After extraction, the aspirate is transferred into the PXP System and processed in a centrifuge to compartmentalize the aspirate into three separate chambers within the Disposable Cartridge - the central processing chamber, the red blood cell depletion chamber and the harvest chamber. The plasma, nucleated cells and RBCs are all sorted by density to create maximum separation of components. The RBCs are then removed and transferred to the depletion chamber, leaving users with a 6 ml harvest of enriched bone marrow concentrate (containing stem cells, platelets, growth factors) ready to be reintroduced into the patient.

The entire process only takes about twenty minutes from the moment the bone marrow aspirate is placed in the system to the point where it can be reinjected. For added convenience, the automated control module provides users with accurate data tracking and serves as a record for the entire process.

The PXPSystem is a tool for physicians looking for a quick, easy and efficient system for processing bone marrow. It is one of the most innovative systems available on the market and our mission is to make it even better. We are currently working with our partners in the field and evolving our products based on their feedback. Based on their response, we've begun designing a stripped-down version of the PXPSystem that requires less accessories and generates a smaller footprint, while still delivering a high-quality final product. Our applications are being developed with the needs of laboratories and physicians in mind, giving them the resources, they need to better serve their patients.

ThermoGenesis Holdings, Inc. (formerly Cesca Therapeutics Inc.), is a pioneer and market leader in the development and commercialization of automated cell processing technologies for the cell and gene therapy fields. We market a full suite of solutions for automated clinical biobanking, COVID-19 testing, point-of-care applications and large-scale cell processing and manufacturing with a special emphasis on the emerging CAR-T immunotherapy market. We are committed to making the world a healthier place by creating innovative solutions for those in need.

To see our full suiteof automated solutions,please visit the shop portion of our website today.

Disclaimer

Thermogenesis Holdings Inc. published this content on 08 December 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 09 December 2020 18:24:01 UTC

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The Technology Behind Bone Marrow Cellular Processing: The PXP System - Marketscreener.com

CAMBRIDGE, Mass.--(BUSINESS WIRE)--HighPassBio, an ElevateBio portfolio company dedicated to advancing novel targeted T cell immunotherapies, today discussed the ongoing Phase 1 trial of the companys lead product candidate, an engineered T cell receptor (TCR) T cell therapy targeting HA-1 expressing cancer cells in an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting. The Phase 1 clinical trial, which is being conducted by researchers at Fred Hutchinson Cancer Research Center, is designed to assess the feasibility, safety, and efficacy of this novel cell therapy in the treatment of leukemia following hematopoietic stem cell transplant (HSCT).

The prognosis for leukemia patients whove relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse, said Elizabeth Krakow, M.D., MSc., Assistant Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, principal investigator of the study, and presenting author. We have observed early promising indicators of anti-leukemic activity following treatment in this trial. We are eager to expand the trial to additional patients as we continue to research the feasibility, safety, and efficacy of this approach.

The abstract for the presentation titled Phase 1 Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress, can be found on the ASH website under the abstract number 137726.

To date, four patients, including one pediatric patient, have received a total of six infusions in the Phase 1 clinical trial. Patient characteristic data was shared in the oral presentation at ASH, including documented HA-1 TCR T cell persistence in blood and bone marrow up to 18 months. In some patients, clear in vivo anti-leukemic activity was observed at the first dose level, including a subject with aggressive, highly refractory T-ALL and early post-HCT relapse. No significant toxicities attributed to the T cells have been observed, including no infusion reactions or evidence of cytokine release syndrome or graft versus host disease.

The Phase 1 clinical trial is currently recruiting adult and pediatric patients who have residual disease or relapsed leukemia or related conditions following HSCT. As part of the trial, transplant patients and prospective donors may be recruited to participate in the genetic screening portion to determine eligibility. More details are available on clinicaltrials.gov under the study ID number NCT03326921.

About TCR-Engineered T Cell Therapy

A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the bodys immune system to respond to fight off and kill the tumor cells.

Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease.

Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patients native cells, and not by the cells from the stem cell transplant donor. HA-1, a known minor histocompatibility antigen, is expressed predominantly or exclusively on hematopoietic cells, including leukemic cells. There is evidence that T cells specific for HA-1 can induce a potent and selective antileukemic effect. HA-1 TCR T cell therapy is a new investigational immunotherapy for the management of post transplantation leukemia relapse.

About Leukemia post HSCT Treatment and the Risk of Relapse

Leukemia, a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, is the tenth most common type of cancer in the U.S. with an estimated 60,140 new cases and 24,400 deaths in 2016. Leukemia arises from uncontrolled proliferation of a specific type of hematopoietic (blood) cell that is critical for a functional immune system. As a result, when patients are given very high doses of chemotherapy to eradicate leukemic cells, most normal cells are killed as well, necessitating a transplant of hematopoietic stem cells from a donor to reconstitute the patients bone marrow and circulating hematopoietic cells. In some cases, the transplanted T cells from the donor can also recognize and eliminate the hematopoietic cells, including leukemia, from the recipient, thus preventing relapse. This can be described as a graft versus leukemia effect. Other hematologic disorders related to leukemia, like myelodysplastic syndrome (MDS), can also be treated in this way.

While HSCT can be curative, it is estimated that 25-50 percent of HSCT recipients relapse; leukemia relapse remains the major cause of allogeneic HSCT failure, and the prognosis for patients with post-HCT relapse is poor. Relapse occurs following allogeneic HSCT in approximately one-third of patients with acute leukemia who undergo the procedure, and most patients subsequently die of their disease.

About HighPassBio

HighPassBio, an ElevateBio portfolio company, is working to advance a novel approach to treating hematological malignancies by leveraging T cell receptor (TCR)-engineered T cells, known as TCR T cells. The companys lead program is designed to treat or potentially prevent relapse of leukemia in patients who have undergone hematopoietic stem cell transplant (HSCT). The technology was born out of research conducted at Fred Hutchinson Cancer Research Center by world renowned expert, Dr. Marie Bleakley.

About ElevateBio

ElevateBio, LLC, is a Cambridge-based creator and operator of a portfolio of innovative cell and gene therapy companies. It begins with an environment where scientific inventors can transform their visions for cell and gene therapies into reality for patients with devastating and life-threatening diseases. Working with leading academic researchers, medical centers, and corporate partners, ElevateBios team of scientists, drug developers, and company builders are creating a portfolio of therapeutics companies that are changing the face of cell and gene therapy and regenerative medicine. Core to ElevateBios vision is BaseCamp, a centralized state-of-the-art innovation and manufacturing center, providing fully integrated capabilities, including basic and translational research, process development, clinical development, cGMP manufacturing, and regulatory affairs across multiple cell and gene therapy and regenerative medicine technology platforms. ElevateBio portfolio companies, as well as select strategic partners, are supported by ElevateBio BaseCamp in the advancement of novel cell and gene therapies.

ElevateBios investors include F2 Ventures, MPM Capital, EcoR1 Capital, Redmile Group, Samsara BioCapital, The Invus Group, Surveyor Capital (A Citadel company), EDBI, and Vertex Ventures.

ElevateBio is headquartered in Cambridge, Mass, with ElevateBio BaseCamp located in Waltham, Mass. For more information, please visit http://www.elevate.bio.

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ElevateBio's HighPassBio Presents on Novel T Cell Receptor Cell Therapy for Leukemia Relapse at 62nd Annual ASH Meeting - Business Wire

This weekend brought some really significant news in the long-running effort to use gene editing to treat human disease. As most readers will have heard, Boston Childrens Hospital and a Vertex/CRISPR effort both published papers in the NEJM addressing sickle-cell anemia and beta-thalassemia. (Update: edit to fix attribution).

These diseases have long been linked when it comes to gene therapy ideas, because both of them have defects in the hemoglobin protein as their cause. And its long been thought that both could be treated by getting adults to re-express the fetal hemoglobin protein its on a different gene entirely, and thus does not have any of the genetic problems that affect the adult hemoglobin gene. The normal course of events is for babies to stop expressing the fetal form and switch over to regular hemoglobin, and its been worked out that a particular transcription factor called BCL11a is a key player in that transcriptional repression of the fetal hemoglobin gene. That plays right into the usual way that we tend to think about therapeutic possibilities: whether its enzymes, receptors, or expression of whole proteins, we have a lot more tools to mess things up and interrupt processes than we have to make them run faster or better. So the possibility of interrupting BCL11as function has been a tempting one for many years.

Its hard to do by traditional means, though. (Full disclosure: I have, at different times in my career, been involved with such efforts, but none have ever come near the clinic.) Transcription factors are notoriously hard to get a handle on with small molecule therapeutics, and many unsuccessful runs have been taken at BCL11a ligands to try to interrupt its functions in one way or another. My general impression is that the protein doesnt much care about recognizing small-molecule ligands (and its far from the only one in that category, for sure). Youd think that if you ran a few hundred thousand (or a few million) various molecules past any given protein that youd find a few of them that bind to it, but that assumption is too optimistic for most transcription factors. Youre also going to have a hard row to hoe (to use an old Arkansas expression) if you try to break up their interactions with their DNA binding sites: a significant amount of capital has gone down the chute trying to get that to work, with (as far as I can tell) not much to show for it.

Theres another complication: BCL11a has a lot of other functions. Every protein has a lot of other functions, but for transcription factors, the issue can be especially fraught. If you had a small molecule that really did interfere with its activity, what would happen if you just took a stiff dose of it? Probably a number of things, including some interesting (and not necessarily welcome) surprises. There have been a number of ideas about how to get around this problem, but a problem it is.

So its on to biological mechanisms. The BCH team reports on using RNA interference to do the job they get cells to express a short hairpin RNA that shuts down production of BCL11a protein, with some microRNA work to target this to the right cell lines. And the Vertex/CRISPR team, naturally, uses CRISPR itself to go in and inactivate the BCL11a gene directly. Both approaches take (and have to take) a similar pathway, which is difficult and expensive, but still the best shot at such therapies that we have. You want the fetal hemoglobin expressed in red blood cells, naturally, and red blood cells come from CD34+ stem cells in the bone marrow. Even if you havent thought about this, you might see where its going: you take a bone marrow sample, isolate these cells, and then do your genetic manipulation to them ex vivo. Once youve got a population of appropriately re-engineered cells ready to go, you go kill off the bone marrow in the patient and put the reworked cells back in, so theyre the only source there for red blood cells at all. A bone marrow transplant, in other words a pretty grueling process, but definitely not as much as having some sort of blood-cell-driven cancer (where the therapy uses compatible donor cells from someone else without such a problem), or as much as having full-on sickle cell disease or tranfusion-dependent thalassemia.

You can also see how this is a perfect setup for gene therapy: theres a defined population of cells that you need to treat, which are available in a specific tissue via a well-worked-out procedure. The problem youre trying to correct is extremely well understood in fact, it was the first disease ever characterized (by Linus Pauling in 1949) as purely due to a genetic defect . And the patients own tissue is vulnerable to chemotherapy agents that will wipe out the existing cell population, in another well-worked-out protocol, giving the newly reworked cells an open landscape to expand in. You have the chance for a clean swap on a defined target, which is quite rare. In too many other cases the problem turns out to involve a fuzzy mass of genetic factors and environmental ones, none of which by themselves account for the disease symptoms, or the tissue doesnt allow you to isolate the defective cells easily or doesnt allow you to clear them out for any new ones you might generate, and so on.

Both the Vertex/CRISPR and BCH techniques seem to work and in fact, to work very well. There are now people walking around, many months after these treatments, who were severely ill but now appear to be cured. Thats not a word we get to use very often. They are producing enough fetal hemoglobin, more than enough to make their symptoms completely disappear no attacks, no transfusions, just normal life. And so far there have been no side effects due to the altered stem cells. An earlier strategy from Bluebird (involving addition of a gene for a modified adult hemoglobin) also seems to be holding up.

These are revolutionary proofs of concept, but at the same time, they are not going to change the course of these diseases in the world not right now, anyway. Bone marrow transfusion is of course a complex process that costs a great deal and can only be done in places with advanced medical facilities. But what weve established is that anything that can cause fetal hemoglobin to be expressed should indeed cure these diseases that idea has been de-risked. As has the general idea of doing such genetic alteration in defined adult tissues (either RNA interference or CRISPR). From here, we try to make these things easier, cheaper and more general, to come up with new ways of realizing these same goals now that we know that they do what we hoped that they would. This work is already underway new ways to target the affected cell populations rather than flat-out chemotherapy assault, new ways to deliver the genetically altered cells (or to produce them on site in the patients), ways to make the switchover between the two more gradual, and so on. There are lot of possible ways, and we now know where were going.

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Gene Therapy, Absolutely and For Real | In the Pipeline - Science Magazine

WASHINGTON, Dec. 8, 2020 /PRNewswire/ --Genetic mutations linked with cancer can occur during childhood or even before birth and proliferate in the body for many years before causing cancer symptoms, according to a new study. The study, which traced the genetic origins of a blood cancer in 10 individuals, suggests there may be untapped opportunities to detect cancer warning signs much earlier and potentially intervene to prevent or slow cancer development.

"Our preliminary findings show these cancer driver mutations were often acquired in childhood, many decades before the cancer diagnosis," said senior study authorJyoti Nangalia, MD,of the Wellcome Sanger Institute and University of Cambridge. "Our results finally answer the common question posed by patients, 'How long has this cancer been growing?' as we were able to study how these particular cancers developed over the entire lifetime of individual patients."

The researchers analyzed bone marrow and blood samples from 10 people with Philadelphia-negative myeloproliferative neoplasms, a type of cancer that causes stem cells in the bone marrow to produce too many blood cells. In the majority of patients, this cancer is driven by a genetic mutation called JAK2V617F. By assessing JAK2V617F, other cancer-linked mutations and hundreds of thousands of other mutations that a person naturally acquires throughout life, the researchers were able to trace the ancestry of different blood cells and estimate the time at which each patient acquired JAK2V617F and other important mutations.

They determined that, in these 10 patients, the first cancer-linked mutations emerged as early as a few weeks after the start of life and up to the first decade of childhood despite clinical disease presenting many decades later in life.

"We were not expecting this," said Dr. Nangalia. "In fact, in one patient, the JAK2 mutation was acquired more than 50 years before their diagnosis."

While it is often assumed that most cancers are diagnosed within a few years of their emergence, the findings point to a more gradual, lifelong process in which a single cell acquires a cancer-linked mutation early in life and then slowly grows over decades, ultimately leading to cancer.

"Some of these cancer-linked mutations are found in healthy individuals as we get older, suggesting that aging causes them," said Dr. Nangalia. "However, aging per se doesn't drive such growth it simply takes a long time for the clones to grow." Sometimes, the growing clones pick up additional cancer-linked mutations along the way, accelerating their growth, researchers found.

"For these patients, we calculated how many of these cancer clones would have been present in the past, and our results suggest that these clones may have been detectable up to 10 to 40 years before diagnosis," said Dr. Nangalia. "In addition to detecting the mutations, the rate at which the mutated clones grew was also very important in determining whether, and when, cancer develops." The findings suggest that genetic testing could help identify people at risk for cancer much earlier than current methods allow, according to researchers.

The next steps would be to understand the factors that influence the different rates of cancer growth and determine whether there could be ways to intervene and slow the growth of cells with cancer-linked mutations. The researchers say their method for pinpointing the origin of this blood cancer could also be applied to other mutations and other blood cancers. "Understanding the timelines of development of different cancers is critical for efforts aimed at early cancer detection and prevention," said Dr. Nangalia.

Jyoti Nangalia, MBBChir,Wellcome Sanger Institute and University of Cambridge, will present this study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

SOURCE American Society of Hematology

http://www.hematology.org

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Researchers Trace the Origin of Blood Cancer to Early Childhood, Decades before Diagnosis - PRNewswire

What started out as a journey to better understand regulatory T cells has now led to an intriguing approach with an investigational cell therapy designed to prevent the risk of graft-versus-host disease (GVHD) and to improve relapse-free survival rates in patients undergoing hematopoietic stem cell transplantation (HSCT).

Data of a phase 1/2 trial recently showed that the first-generation precision cell treatment Orca-T compared with a historical control of standard HSCT demonstrated faster neutrophil (median, 12 days vs 14 days; P < .0001) and platelet engraftment (median, 11 days vs 17 days; P < .0001), decreased incidence of grade 2 or higher GVHD at 100 days (10% vs 30%, P = .005) and chronic GVHD at 1 year (3% vs 46%, P = .0002).1,2

The 1-year GVHD-free and GVHD relapse-free survival (GRFS) rates were 75% with the use of Orca-T vs 31% with standard HSCT (P < .0001). The comparator cohort was derived from contemporaneous patients who had been treated at Stanford University with a conventional allograft.

Along with feasibility of the approach, the results also highlight how Orca-T demonstrates potent anti-leukemic activity in patients who have active disease at HSCT, which suggests that the decrease of GVHD does not impact graft-vs-leukemia (GvL).

That is the most exciting part about the Orca-T story; it is the ability to do this with precision, with speed, and to export it to other sites. The results are intriguing, and very supportive, said Robert Negrin, a professor of medicine (blood and marrow transplantation), and chief of the Division of Blood and Marrow Transplantation at Stanford University.

In an interview with OncLive, Negrin, who is senior author on the trial, shared the evolution of Orca-T as a novel approach to HSCT, highlighted his robust experience with using this cell therapy at Stanford University, and how Orca-T is a potential prevention method for GVHD.

OncLive: Please provide some background to this therapeutic approach. What is the mechanism of action? How is it effective in patients undergoing transplant?

Negrin: This whole idea came from mouse studies many, many years ago, where we identified GVHD as being a dysregulated immune reaction that just keeps going, and going, and going. Like you and I, when we react to something, we have a reactionlet's say, influenza. Our body responds, and then we stop reacting and you get better. With GVHD, what we noticed in using a bioluminescent animal model is that the alloreactive T cells just keep going, going, and going and are unrelenting in mice, just like in people. The problem is very similar and affects certain organs in a very similar way.

Therefore, we went about trying to understand the use of so-called regulatory cells. These are cells that everybody has that help control immune reactions. We just applied them in this clinical scenario, first in mice work done by Matthias Edinger, MD, when he was a postdoctoral fellow many years ago [and other researchers]. All of them were very actively involved in these studies, and showed, somewhat surprisingly, that the administration of regulatory T cells could control this dysregulated immune response that we called GVHD.

Probably more surprising was that, at least in the animal models, it also allowed for the benefits of transplant, namely, the graft-vs-tumor effect and better immune recovery. This was in large part because GVHD also impacts the immune repertoire and where the immunity is developed in the recipient.

All of this was very nice in mouse models and was very elegant. We did a lot of studies, published a number of nice papers, and thought this would be a great idea because it sort of solved, or at least addressed, the principal problems after bone marrow transplantationnamely, avoidance of GVHD yet retention of graft-versus-tumor effects and better immunity. A lot of times, people say, "Oh, that sounds good in mice, but, that's too good to be true." And, theyll ask, "Will that all work in people?"

Where did the biggest challenges lie in this approach?

The big challenge came about to try to apply this to patients. We also have one other interesting point that is relevant. If we gave the regulatory T cells first, before the so-called conventional CD4+/CD8+ cells, that allowed for a lower dose of regulatory T cells. This is because a big challenge is the paucity of these cells; you and I don't have that many.

Then, the other big challenge was the technical ability to isolate in cells. What we do in mice is cell sorting, which is a standard technology. But, that was not developed in people because we're bigthere are a lot of cells, and cell sorting is rather slow, and it's very specific. To get enough cells takes a really long time. It's somewhat of a heroic thing to do in people, to get the adequate amount ourselves; of course, we don't really know what this proper cell dose is.

However, what we thought we learned was that the ratio of conventional to regulatory T cells was the key component. Also, if you give the regulatory T cells first, you can get fewer numbers. Those are things you can do in transplant. You can get the cell from the donor, and you can give cells in a certain sequence; all of those things are very doable. It seemed like an attractive thing to do in patients.

Then, the question was: Does it work? There are 3 groups that have really pioneered this work. The first study came from the University of Perugia in Italy. They did this in haploidentical transplantation; you cannot avoid immunosuppression in haploidentical transplants. They were able to show in several nice papers that you could do this strategy, and seemingly, get away with low risk of GVHD, and also low relapse. This is because the other issue is: how do you measure the graft-vs-tumor effect? There is no assay, and we have no test; you have to wait and see who relapses and who doesn't. Therefore, they also showed rather convincingly that you could reduce GVHD risk, yet, there was a very low risk of relapse in their high-risk patient population. Those were very important [data].

Another study from the University of Minnesota did this with umbilical cord blood. They expanded the regulatory T cells from a third cord blood unit, which is somewhat heroicit is another level of complexity to isolate the cells and then expand them. We did this in matched donorseither matched siblings or matched unrelated donors. We published a paper in JCI Insight several years ago showing the initial results, and they look quite favorable.

Therefore, what I think is most exciting about what Orca Bio has done is they are developing technology to isolate the cells more quickly, to be able to do this on a clinical scale, with precision, and with speed. Also, [they are developing the technology] to be able to distribute it to anybody, because the criticism of all these studies is that, "Oh, that's nice. But, this is a single-institution study. Is this really true? Can this be exported? Could this be something that [an organization] other than these [individual] centers are really focused in this area and have developed these technologies could really do? Orca Bio is developing the technology, and improving the technology, because it's still very cumbersome, and exporting the technology so that you could do this, theoretically, at any center.

That's what I think is most exciting about the Orca Bio abstract; it is demonstrating that this can be done. It certainly opens the door to prevention of GVHD. As we move into an era of using cell-based therapeutics, now, this opens up many other possibilities, because you use these regulatory cells and autoimmune disorders and organ transplant tolerance. There are many other cell types that have potential clinical utility, but getting them, and purifying them, is a big challenge. There are many other possibilities that one could think of.

Obviously, more time will be required to follow these patients, but they certainly are supportive of the idea that you can improve overall outcomes using this strategy. That's what we hope to be able to demonstrate further.

Please focus on the scalability of this approach. Through these types of collaborations, how do you see Orca-T potentially moving through the FDA pipeline?

In academia, we don't develop drugs. It's too much, we don't have the resources, we don't have the capability, and we don't have the monitoring capability that is required for multi-institutional studies. Where these commercial partners come in is, they can raise money for interesting concepts, which Orca Bio has done, and they can export this to other centers, and that's critically important.

As we've seen in the CAR T-cell [therapy] world, that can be a quite successful commercial business. Also going through the process of an FDA approvalwhich Orca Bio is moving along in that processand getting the right designations is critically important to commercial entities. In academia, it's important to us, but that's just not our focus.

We don't have the resources around, the people and the expertise to really drive things through that process. We're good at developing the studies and getting FDA approvals, and [investigational new drug applications], but not really [good at] developing drugs as a commercial entity. This collaboration is key to doing this successfully; for example, at Orca Bio, [they have] technology to separate cells more efficiently and effectively. They also have the resources to do a multi-institutional clinical trial, and the expertise to move something through and present it to the FDA. Those are key components.

Could you expand on the study and respective data from this phase 1/2 trial?

Here at Stanford Cancer Institute, we did find in our patients that giving low doses of immunosuppressive medications with a single agent seem to improve the outcomes, and it's remarkable how well these patients have gone through the transplant. It's a little bit hard to appreciate an abstract until you take care of these patients, and many of them just sort of move to the transplant with relatively little challenges. We have not seen greater risks of things like infection [or] disease recurrence; those are obviously things that will be followed.

When we look at the 1-year GVHD relapse-free survival rate, which is an endpoint that most transplant studies would agree is the most important end point, the overall outcomes are much more favorable compared with a historical control group.

The data are very encouraging, and the overall outcomes look very strong in a reasonable number of patients now. We think it's important for the community to hear about it, and to get it on everybody's radar, and be excited about trying to move this forward as a more standard therapy. This is still a clinical trial, so it's not, it's not part of any standard therapies yet. We are using this quite regularly and have been very encouraged by the ease of which patients go through the transplant. It's still an allogeneic transplant; there still are many challenges there. However, these patients seem to be doing quite well, we're very encouraged, and so we keep going.

How does this approach impact patient outcomes as it relates to quality of life (QoL)?

The hard end points of 1-year relapse-free survival is obviously the most important to patients. However, going through an allogeneic transplant is obviously an incredibly difficult thing. Fortunately, I've only seen it [from] the doctor side, not [as a] patient.

However, I've seen many, many patients, and the quality of their life as they go through this experience is very important to all of us. As we saw these patients go through these studies, we felt like we were capturing something that was really important, and that is the ease [at which] many patients went through this experience, which just seemed different. It's hard to capture that.

It's really important for patients to speak and, and the way patients speak is in different ways. One way is through the QoL measures that they answer. This is [what they find] important, this is what they experiencednot what we say is happening. That's really important to hear that voice too. Those are data we're trying to collect. It's not so easy, because going through a bone marrow transplant is a poor QoL for everybody. But, by just to trying to capture this, [Orca-T seems] better than what we what we thought.

How has this changed the mindset of cell-based approaches in the community?

What has changed is the belief in the concept of cell-based therapies. A lot of these things are somewhat fanciful. It is also important to show that we can translate from an animal model [to a human]. There is a lot of criticism of animal modeling, because people say, "Well, it's nice for animal models, but it doesn't really translate into the clinic." Actually, my view is that because we don't actually follow the animal models, there are many compromises one needs to make. When you translate studies from animals to humans, there are many differences, and it's really important to try to follow them as carefully as you can within the limitations of what is possible. We were very engaged in that and tried to follow as carefully as we could. To me, that is very encouragingthat you can study things in animals that generate new concepts and be able to translate that into a clinical trial.

Obviously, with all of the caveats of an early-phase clinical trial, more time needs to pass, more patients to be treated, and you need to export [the treatment] to other centers. That's a really important point, because there are many things that get lost because, "it's too complicated. It's too expensive. People can't do it." I don't think anybody can do high-speed cell sorting, as a clinical project in a standard or standard cell-processing laboratory. It's above the level of what most processing laboratories can do.

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Negrin Shines Light on the Orca-T Story in GVHD - OncLive

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, today announced final clinical results from its earlier completed Phase 1 clinical trial as well as development updates for its MGTA-145 stem cell mobilization therapy, including commencement of enrollment in a Phase 2 clinical trial in multiple myeloma, and its plans for a Phase 2 clinical trial in allogeneic stem cell transplant for patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS). The company also previously announced a clinical collaboration with bluebird bio to evaluate MGTA-145 for mobilizing and collecting stem cells in adults and adolescents with sickle cell disease (SCD). Additional preclinical results were also presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place virtually from December 5-8, 2020, on the Magenta conditioning platform, including MGTA-117 program, which is a targeted antibody-drug conjugate (ADC) to prepare patients for stem cell transplant.

MGTA-145 Advancement to Phase 2 Development in Blood Cancers

The company announced that enrollment has started and is ongoing in a Phase 2 clinical trial of MGTA-145, used in combination with plerixafor, to mobilize and collect stem cells for autologous stem cell transplantation of multiple myeloma patients at Stanford University. Magenta expects that this trial will provide patient-level data on stem cell mobilization and collection, characteristics of the mobilized graft and engraftment in patients with multiple myeloma.

Additionally, through a collaboration with the National Marrow Donor Program/Be The Match, a global leader in facilitating allogeneic hematopoietic stem cell transplantation, Magenta plans to initiate a Phase 2 clinical trial in early 2021 using MGTA-145 to mobilize and collect stem cells from allogeneic donors for transplant in patients with AML, ALL and MDS. Allogeneic stem cell transplant provides a potentially curative therapeutic option for patients with these diseases. This clinical trial will evaluate stem cell mobilization, collection, cell quality, engraftment and the potential for reduced Graft-versus-Host Disease (GvHD), which is of particular importance in the allogeneic transplant setting.

MGTA-145 in Sickle Cell Disease

Magenta Therapeutics recently announced an exclusive clinical collaboration with bluebird bio to evaluate the utility of MGTA-145, in combination with plerixafor, for the mobilization and collection of stem cells in adults and adolescents with SCD.

The data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as the preferred mobilization regimen for patients with SCD. bluebird bios experience with plerixafor as a mobilization agent in SCD aligns with Magentas combination therapy approach, utilizing MGTA-145 plus plerixafor with potential for safe, rapid and reliable mobilization of sufficient quantities of high-quality stem cells to improve outcomes associated with stem cell transplantation.

MGTA-145 Presentations at ASH

Magenta presented final clinical data from its MGTA-145 stem cell mobilization Phase 1 clinical trial in healthy volunteers at the ASH Annual Meeting. All primary and secondary endpoints were met in the study completed earlier this year.

The results demonstrate that a single dose of MGTA-145, in combination with plerixafor, rapidly and reliably mobilized high numbers of stem cells in a single day without the need for G-CSF for potential use in diseases that can benefit from autologous and/or allogeneic stem cell transplantation. The additional data also offer further confirmation that MGTA-145, in combination with plerixafor, was well tolerated and provides a rapid and reliable method to obtain large numbers of hematopoietic stem cells. Transplant of these cells in preclinical models resulted in enhanced, durable engraftment, in addition to highly immunosuppressive properties, leading to reduced GvHD.

Results from this study provide a robust dataset and proof of concept that MGTA-145, in combination with plerixafor, provides rapid and robust mobilization of stem cells and that these cells have better engraftment potential, are able to be gene modified and engraft and reduce GvHD in preclinical models compared to cells mobilized with other available agents. The data reinforce the availability of compelling opportunities for development in both the autologous and allogeneic transplant settings, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics.

The data were presented by Steven M. Devine, MD, Chief Medical Officer of the National Marrow Donor Program/Be The Match and Associate Scientific Director of the CIBMTR (Center for International Blood and Marrow Transplant Research).

Conditioning Program (MGTA-117 and CD45-ADC) Presentations at ASH

Magenta also provided updates on its conditioning platform at the ASH Annual Meeting, including MGTA-117 and CD45-ADC programs. Preclinical data from a study of MGTA-117 demonstrate that it is an effective, potent conditioning agent for transplant with anti-leukemic activity, significantly decreasing tumor burdens, leading to delayed tumor growth and increased median survival rates in animal models of AML. Ongoing GLP toxicology and GMP manufacturing progress continue to be supportive of advancing MGTA-117 towards an IND filing in AML and MDS.

Additionally, preclinical data from a study of Magentas CD45-ADC, a CD45-targeted conditioning agent designed to remove the cells that cause autoimmune diseases to enable curative immune reset, demonstrated the ability to achieve successful outcomes as a single agent in the most challenging disease model through fully mismatched allogeneic hematopoietic stem cell transplant, where only radiation or combinations of toxic chemotherapies are available, potentially providing patients the option of a reduced toxicity conditioning regimen. The company continues to evaluate this program preclinically.

About MGTA-145

MGTA-145 is being developed in combination with plerixafor to harness complementary chemokine mechanisms to mobilize hematopoietic stem cells for collection and transplantation. This new combination has the potential to be the preferred mobilization regimen for rapid and reliable mobilization and collection of hematopoietic stem cells to improve outcomes in autologous and allogeneic stem cell transplantation, which can rebuild a healthy immune system for patients with blood cancers, genetic diseases and autoimmune disorders.

MGTA-145 has the potential to replace the current standard of care for patients and allogeneic donors who currently rely on the use of granulocyte-colony stimulating factor (G-CSF) alone or in combination with plerixafor, which can take up to five days or longer to mobilize sufficient numbers of stem cells, often resulting in significant bone pain and other side effects.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with blood cancer, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics Announces Commencement of First Phase 2 Clinical Trial of MGTA-145 for Stem Cell Mobilization, Oral Presentation of MGTA-145...

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

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

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

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

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

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

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

About the Phase 2 trial of NG-01

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

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

About Multiple Sclerosis

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

About NeuroGenesis

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

About Hadassah and Hadasit

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

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

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

SOURCE NeuroGenesis

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

The following article features coverage from the ASH 2020 virtual meeting. Click here to read more of Oncology Nurse Advisors conference coverage.

Patients who received venetoclax with azacytidine for the treatment of higher-risk myelodysplastic syndrome (HR-MDS) had high overall survival rates and clinically meaningful improvements of dyspnea and fatigue through 48 weeks. These findings were presented during the American Society of Hematology (ASH) 62nd Annual Meeting and Exposition.

Jacqueline S. Garcia, MD, coauthor of this study, explained the mechanism of this therapy. Apoptosis is normally under tight control by the interaction between pro-survival and pro-biotic proteins. In HR-MDS, myeloblasts overexpress BCL-2 and blasts are generally highly prone to pro-apoptotic proteins. Azacytidine indirectly decreases other apoptotic proteins, which sensitizes cells to venetoclax. Venetoclax is a BCL-2 inhibitor, which induces death. Thus, these drugs have the potential to irreversibly commit the cell to death.

Patients (N=78) with HR-MDS who were not candidates for intensive chemotherapy were recruited for this ongoing, open-label, dose-escalation, phase 1b study. Study participants received venetoclax 400 or 800 mg for 28 days followed by an escalating dose (100, 200, and 400 mg) for 14 days in a 28-day cycle with azacitidine 75 mg/m2 subcutaneously or intravenously administered on the first 7 days of each cycle. Participants were assessed for adverse events and efficacy.

Patient group was 75% men, median age 71 years (range, 26 to 85) and 56% had very high-risk disease.

Of the 31 patients with baseline marrow data, the most frequent mutations were located in tumor protein p53 (TP53; 35.5%), additional sex combs like 1 (ASXL1; 19.4%), and stromal antigen 2 (STAG2; 16.1%).

All participants experienced at least 1 adverse event during the study. The most commonly observed events were constipation (54%), nausea (55%), and neutropenia (83%). Adverse events grade 3 or higher were experienced by 96% of patients and included febrile neutropenia (49%) and thrombocytopenia (42%). Few infections were observed, likely due to the antibiotic prophylaxis.

At 30 days, the mortality rate was 1% and 1.3% experienced disease progression. A total of 16 patients received post-study transplants (bone marrow, 7 patients; stem cell, 9 patients).

The objective response rate was 79%; in which 39.7% entered into complete remission, 39.7% into marrow complete remission, and 14.1% had stable disease.

The median duration of response was 12.9 months (range, 12.1 to 16.8), and among those who achieved complete remission, the median duration of response after remission was 13.8 months (range, 6.5 to 20.9). The median time to complete remission was 2.6 months (range, 1.2 to 19.6).

Physical function through 48 weeks was generally maintained and fatigue, dyspnea, and global health quality of life were improved among patients who received 400 mg of venetoclax for 14 days.

This study was limited by its small sample size and short duration; however, this study was still on-going, and a phase 3 trial has begun.

These results indicated venetoclax with azacitidine was efficacious, allowing for maintenance of physical functioning for up to 48 weeks among patients with HR-MDS who were not candidates for intensive chemotherapy.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Garcia JS, Wei AH, Borate U, et al. Safety, efficacy, and patient-reported outcomes of venetoclax in combination with azacitidine for the treatment of patients with higher-risk myelodysplastic syndrome: a phase 1b study. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstr 656.

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Venetoclax/Azacitidine Combination Efficacious for the Treatment of Older Patients With Higher-Risk Myelodysplastic Syndrome - Oncology Nurse Advisor

NEW YORK--(BUSINESS WIRE)--Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, today presents updated interim data from its Fanconi Anemia (FA) and Leukocyte Adhesion Deficiency-I (LAD-I) programs at the 62nd American Society of Hematology (ASH) Annual Meeting. The data are highlighted in two oral presentations.

We are highly pleased with the data presented at ASH demonstrating ongoing evidence of efficacy and durability using Process B in both FA and LAD-I as we move towards potential registration, said Gaurav Shah, M.D., Chief Executive Officer and President of Rocket. Follow-up data from the Phase 1 and 2 trials for FA continue to support RP-L102 as a potential hematologic treatment option in the absence of cytotoxic conditioning. In five of the seven patients treated as of October 2020, there was evidence of engraftment. In addition, stabilization of peripheral blood counts in two of the three patients with at least 12-month follow-up, which declined substantially in these patients prior to gene therapy, suggests a halt in bone marrow failure progression. We look forward to reporting longer-term follow-up on these patients in the first half of 2021.

Dr. Shah continued, Additionally, we continue to see encouraging evidence of efficacy for RP-L201 for the treatment of LAD-I. Patients have shown sustained CD18 expression of 23% to 40%, far exceeding the 4-10% threshold associated with survival into adulthood. These data, on top of our exciting results from our lentiviral program for PKD, show our steady progress across three of our five gene therapy programs. We are proud of this progress and are committed to advancing our investigational gene therapies through development for patients and families facing these devastating disorders.

Key findings and details for each presentation are highlighted below. To access the presentations at the conclusion of the oral presentation, please visit: https://www.rocketpharma.com/ash-presentations/

Gene Therapy for Fanconi Anemia, Complementation Group A: Updated Results from Ongoing Global Clinical Studies of RP-L102The data presented in the oral presentation are from seven of the nine patients treated as of the cutoff date of October 2020 in both the U.S. Phase 1 and global Phase 2 studies of RP-L102 for FA. Seven patients had follow-up data of at least 2-months, and three of the seven patients had been followed for 12-months or longer. Key highlights from the presentation include:

Presentation Details:Title: Gene Therapy for Fanconi Anemia, Complementation Group A: Updated Results from Ongoing Global Clinical Studies of RP-L102Session Title: Gene Editing, Therapy and Transfer IPresenter: Agnieszka Czechowicz, M.D., Ph.D., Assistant Professor of Pediatrics, Division of Stem Cell Transplantation, Stanford University School of MedicineSession Date: Monday, December 7, 2020Session Time: 11:30 a.m. - 1:00 p.m. (Pacific Time)Presentation Time: 12:15 p.m. (Pacific Time)

Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Results from Phase 1The data presented in the oral presentation are from three pediatric patients with severe LAD-I, as defined by CD18 expression of less than 2%. The patients were treated with RP-L201, Rockets ex-vivo lentiviral gene therapy candidate. Patient L201-003-1001 was 9-years of age at enrollment and had been followed for 12-months as of a cutoff date of November 2020. Patient L201-003-1004 was 3-years of age at enrollment and had been followed for over 6-months. Patient L201-003-2006 was 7-months of age at enrollment and was recently treated with RP-L201. Key highlights from the presentation include:

Rockets LAD-I research is made possible by a grant from the California Institute for Regenerative Medicine (Grant Number CLIN2-11480). The contents of this press release are solely the responsibility of Rocket and do not necessarily represent the official views of CIRM or any other agency of the State of California.

Presentation Details:Title: Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Results from Phase 1Session Title: Gene Editing, Therapy and Transfer IPresenter: Donald Kohn, M.D., Professor of Microbiology, Immunology and Molecular Genetics, Pediatrics (Hematology/Oncology), Molecular and Medical Pharmacology, and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los AngelesSession Date: Monday, December 7, 2020Session Time: 11:30 a.m. - 1:00 p.m. (Pacific Time)Presentation Time: 12:30 p.m. (Pacific Time)

Conference Call DetailsRocket management will host a conference call and webcast today December 7, at 6:00 p.m. EST. To access the call and webcast, please click here. The webcast replay will be available on the Rocket website following the completion of the call.

Investors may listen to the call by dialing (866) 866-1333 from locations in the United States or +1 (404) 260-1421 from outside the United States. Please refer to conference ID number 50038102

About Fanconi AnemiaFanconi Anemia (FA) is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic hematopoietic stem cell transplantation (HSCT), when available, corrects the hematologic component of FA, but requires myeloablative conditioning. Graft-versus-host disease, a known complication of allogeneic HSCT, is associated with an increased risk of solid tumors, mainly squamous cell carcinomas of the head and neck region. Approximately 60-70% of patients with FA have a Fanconi Anemia complementation group A (FANCA) gene mutation, which encodes for a protein essential for DNA repair. Mutation in the FANCA gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress. Increased sensitivity to DNA-alkylating agents such as mitomycin-C (MMC) or diepoxybutane (DEB) is a gold standard test for FA diagnosis. Somatic mosaicism occurs when there is a spontaneous correction of the mutated gene that can lead to stabilization or correction of a FA patients blood counts in the absence of any administered therapy. Somatic mosaicism, often referred to as natural gene therapy provides a strong rationale for the development of FA gene therapy because of the selective growth advantage of gene-corrected hematopoietic stem cells over FA cells.

About Leukocyte Adhesion Deficiency-ISevere Leukocyte Adhesion Deficiency-I (LAD-I) is a rare, autosomal recessive pediatric disease caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is a key protein that facilitates leukocyte adhesion and extravasation from blood vessels to combat infections. As a result, children with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75% prior to the age of 2 and survival beyond the age of 5 is uncommon. There is a high unmet medical need for patients with severe LAD-I.

About Rocket Pharmaceuticals, Inc.Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket) is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, Pyruvate Kinase Deficiency (PKD) a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia and Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. Rockets first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. For more information about Rocket, please visit http://www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking StatementsVarious statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding its guidance for 2020 in light of COVID-19, the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon Disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket's ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rockets ongoing trials, our expectations regarding the delays and impact of COVID-19 on clinical sites, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed November 6, 2020 with the SEC. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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Rocket Pharmaceuticals Presents Positive Clinical Data from its Fanconi Anemia and Leukocyte Adhesion Deficiency-I Programs at the 62nd American...

GERMANTOWN, Md., Dec. 7, 2020 /PRNewswire/ -- Precigen Inc., a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced at the 62nd ASH Annual Meeting and Exposition (Abstract 2864) clinical progress and new data from the ongoing Phase 1/1b clinical study of PRGN-3006UltraCAR-Tin patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) and higher risk myelodysplastic syndrome (MDS) (clinical trial identifier: NCT03927261).

AML is a rapidly progressing disease with poor prognosis and high unmet need. Precigen's UltraCAR-T platform is designed to overcome limitations of currently available chimeric antigen receptor (CAR)-T therapies by utilizing an advanced overnight non-viral gene delivery manufacturing process at a medical center's cGMP facility without the need for ex vivo expansion. Current CAR-T cell therapies are limited due to, inter alia, the prolonged interval between apheresis to product infusion and an exhausted phenotype of T cells resulting from lengthy ex vivo expansion. As announced in November 2020, UltraCAR-T cells for the PRGN-3006 study are now manufacturedovernight using Precigen's proprietary UltraPorator device. PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T simultaneously expressing a CAR specifically targeting CD33; membrane bound IL-15 (mbIL15) for enhanced in vivo expansion and persistence; and a kill switch to conditionally eliminate CAR-T cells for an improved safety profile. CD33 is over-expressed on AML blasts with lesser expression on normal hematopoietic stem cells.

An investigator-initiated, non-randomized Phase 1/1b dose-escalation study to evaluate the safety and maximal tolerated dose of PRGN-3006 UltraCAR-T is currently ongoing in collaboration with the H. Lee Moffitt Cancer Center & Research Institute (Moffitt). The study population includes adult patients ( 18 years) with r/r AML and hypomethylating agent (HMA) failure, higher risk MDS or chronic myelomonocytic leukemia (CMML) patients with 5% blasts. To test the hypothesis that expression of mbIL15 on PRGN-3006 can promote UltraCAR-T cell expansion and persistence without the need for lymphodepletion and improve the overall safety profile, studysubjects receive the PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2). A multicenter expansion of the trial is planned.

Key findings:

A case study of the patient with the longest follow-up as of the data cutoff was also presented. This patient received, one day after gene transfer and without prior lymphodepletion, a very low dose, approximately three hundred thousand UltraCAR-T per kilogram (3 x 105 UltraCAR-T/kg) for a total of only 24 million UltraCAR-T. She is a 69 year old female with secondary AML (sAML) and four prior lines of therapy, including induction chemotherapy (IC), allogenic hematopoietic stem cell transplantation (allo-HSCT), HMA plus venetoclax (HMA+VEN), refractory to all therapy post allo-HSCT. The patient had approximately 40% peripheral blasts and 47% bone marrow blasts at baseline.

Case study findings:

"There is an urgent need for novel therapies for relapsed or refractory AML patients as the median overall survival for this patient population is less than six months. Current CAR-T approaches for AML have faced challenges due to long manufacturing durations resulting in subsequent delays in treatment," said David A. Sallman, MD, of Moffitt and lead investigator for the PRGN-3006 clinical study. "We are encouraged by the initial data, including safety and manufacturing success from patients treated with autologous UltraCAR-T cells, which were manufactured on-site with almost instant turnaround. We are excited by the expansion and continued persistence of PRGN-3006 UltraCAR-T cells in the patient case study for over seven months post-infusion without prior lymphodepletion and are looking forward to higher doses in the lymphodepleted and non-lymphodepletion cohorts."

"Currently commercialized CAR-T therapies have not demonstrated the persistence needed to drive sustained, durable responses," said Helen Sabzevari, PhD, President and CEO of Precigen. "The results from Dr. Sallman's patient case study are particularly encouraging as the patient received a very low dose of cells without any ex vivo expansion or activation and no lymphodepletion, which highlights the importance of membrane bound IL-15 in expansion and persistence of these cells and, we believe, differentiates the UltraCAR-T platform from other CAR-T's. In particular, expansion and persistence of UltraCAR-T cells in the patient's blood through seven months post-infusion show promise for the durability of PRGN-3006. We look forward to providing additional details for the PRGN-3006 study at our upcoming clinical update call this month."

About Acute Myeloid Leukemia (AML)AML is a cancer that starts in the bone marrow, but most often moves into the blood.1 Though consideredrare, AML is among the most common types of leukemia in adults.2 In 2019, it was estimated that 21,450 new cases of AML would be diagnosed in the US.2 AML is uncommon before the age of 45 and the average age of diagnosis is about 68.2 The prognosis for patients with AML is poor with an average 5year survival rate of approximately 25 percent overall, and less than a 5 percent 5year survival rate for patients older than 65.3 Amongst elderly AML patients ( 65 years of age), median survival isshort, ranging from 3.5 months for patients 65 to 74 years of age to 1.4 months for patients 85 years of age.3

About Myelodysplastic Syndrome (MDS)MDS are diseases of the bone marrow generally found in adults in their 70s.4 Incidence in the US is not known for sure, but estimates range from 10,000 each year and higher.4 Using International Prognostic Scoring System (IPSS-R), median survival for MDS patients can vary from less than one year for the "very high" IPSS-R risk group to more than eight years for the "very low" IPSS-R group.4

About PRGN-3006 UltraCAR-TPRGN-3006 UltraCAR-T is a multigenic autologous CAR-T cell treatment utilizing Precigen's non-viral Sleeping Beauty system to simultaneously express a CAR specifically targeting CD33, which is over expressed on acute myeloid leukemia blasts with lesser expression on normal hematopoietic stem cell populations and minimal non-hematopoietic expression; membrane bound IL-15 for enhanced in vivo expansion and persistence; and a kill switch to conditionally eliminate CAR-T cells for animproved safety profile. PRGN-3006 is being evaluated in collaboration with the Moffitt Cancer Center in a nonrandomized, investigatorinitiated Phase 1/1b dose escalation study to evaluate the safety and maximal tolerated dose of PRGN3006 UltraCAR-T (clinical trial identifier: NCT03927261). The study population includes patients with relapsed or refractory acute myeloid leukemia or higher risk myelodysplastic syndrome. The US Food and Drug Administration (FDA) has granted orphan drug designation (ODD) for PRGN-3006 UltraCAR-T in patients with AML.

Precigen: Advancing Medicine with PrecisionPrecigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit http://www.precigen.com or follow us on Twitter @Precigen and LinkedIn.

TrademarksPrecigen, UltraCAR-T, UltraPorator and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking StatementsSome of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company's current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company's business, including the timing and progress of preclinical studies, clinical trials, discovery programs and related milestones, the promise of the Company's portfolio of therapies, and in particular its CAR-T therapies, and the Company's refocus to a healthcare-oriented business. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties, including the possibility that the timeline for the Company's clinical trials might be impacted by the COVID-19 pandemic, and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company's most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

References1 American Cancer Society. What is Acute Myeloid Leukemia (AML)?2 American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML)3 Thein, M., et al., Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer, 2013. 119(15): p.2720-74 American Cancer Society.Key Statistics for Myelodysplastic Syndromes

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SOURCE Precigen, Inc.

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Precigen Presents New Data Supporting the Safety, Clinical Activity, Expansion and Persistence of PRGN-3006 UltraCAR-T at the 62nd ASH Annual Meeting...

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

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

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

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

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

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

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

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

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

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

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

Media Contacts

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

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

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

Thats how Valerie Mitchell of Joliet is expressing the pre-holiday news that her son Owen Buell, 2, is showing no evidence of disease in regards to the neuroblastoma hes been fighting all year.

We are really happy, Mitchell said. I still cannot believe he is cancer-free. Everyone is really overjoyed about it, especially being around Christmastime.

On Friday, Owen had a number of scans including CT MRI, MIBG and an echocardiogram, along with bone marrow and hearing tests. Mitchell said. All scans came back clear, she said.

He fought as hard as he could and beat cancer, Mitchell said.

But Owen must remain cancer-free for the next five years before the word remission can be used, she said. In addition, Owen also has more treatments ahead of him: six months of immunotherapy, which Mitchell said will be extremely painful and hard on the body.

Owen will need a five to six-day stay in the hospital each month and a pain pump just to receive the treatments, Mitchell said. But the treatment is necessary to eliminate any remaining cancer cells in Owens body; otherwise new tumors or spots of cancer may form.

Were all really tired, Mitchell said. But we can push through knowing that hes going to be cancer-free. Its just one more step and then he should be good.

When Owen was diagnosed in February, he had two tumors and 21 spots of cancer, Mitchell said. His father Brian was working a job and a half at the time and he and Mitchell shared the family van.

Since then, Owen has undergone many scans, a central line placement, five rounds of chemotherapy, surgery to remove tumors, a stem cell harvest, two stem cell transplants that required a three-month hospital stay, 12 rounds of radiation and 10 days of being intubated in the hospitals intensive care unit, Mitchell said.

Owen now also has damage to one kidney and high blood pressure, Mitchell said. The COVID-19 pandemic made treatments even harder on Owen and his family, she added, especially since Owen's brothers Elliott and Bentley, age 4.were just 7 and 4 when Owen was diagnosed.

We didn't have the help everyone was offering in fear Owen would catch this virus, Mitchell wrote on her Facebook page. We couldn't go anywhere in between treatment to cheer Owen up. We couldn't bring him into the store to pick out a new toy or get him out of the house. He couldn't go swimming; he couldn't go to any arcades; he couldn't even have his father or siblings by his side undergoing surgery or chemo. It wasn't/ isnt fair that Owen had to suffer as much as he did. But we are happy he is still here.

Mitchell said the family celebrated Owens good news with pizza, cake and silly string. And she said Owen is going to go crazy with happiness when he sees all the Christmas gifts toys theyve bought for him.

In the meantime, Owen is enjoying the holiday season like any other 2-year-old.

Hes already playing with the Christmas tree bulbs, Mitchell said.

Donate to the "Help for baby Owen Buell and his Family" GoFundMe page at bit.ly/3n0MThy.

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Joliet 2-year-old gets pre-holiday gift: tests that show he's cancer-free - The Herald-News

GAITHERSBURG, Md., Dec. 07, 2020 (GLOBE NEWSWIRE) -- NexImmune, a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to employ the bodys own T cells to generate a specific, potent and durable immune response that mimics natural biology, today announced that City of Hopes Monzr Al Malki, M.D., delivered an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition featuring initial data from the Phase 1/2 trial of NEXI-001 in AML. Entitled Preliminary Results of the First-in-Human Study of NEXI-001, a Multi-Antigen Specific CD8+ T Cell Product, in Acute Myeloid Leukemia (AML) Patients with Relapsed Disease after Allogeneic Hematopoietic Cell Transplantation (Allo-HSCT) Demonstrate Early Signs of Safety, Tolerability and Robust Immune Responses, the presentation included responses following a single infusion of the experimental therapy.

These data represent safety and tolerability results from the first five patients treated and reflect a median of four months of follow-up with infusion doses ranging from 50-200 million total T cells. As noted by Dr. Al Malki in his presentation, there have been no cases of acute Graft versus Host Disease (aGvHD), Cytokine Release Syndrome (CRS), immune cells-associated neurological syndromes (ICANs), or infusion related reactions (IRRs) reported to-date, nor have there been any treatment-related adverse events (AEs) observed.

Biomarker data characterizing initial immunologic responses for the first three patients analyzed were also shared. Absolute lymphocyte counts, or ALC, were followed over time after the administration of lymphodepleting therapy, and showed a rapid return to baseline levels for each patient assessed (range 3 to 35 days). In addition, data on T cell reconstitution after lymphodepletion demonstrated that a single infusion of NEXI-001 T cells triggered a broad, rapid and robust immune response, inclusive of both CD8+ and CD4+ T cell types. TCR analysis showed the presence, persistence, expansion and migration of individual NEXI-001 T cell clones from the peripheral blood to the bone marrow of each patient. Finally, the immune phenotype of individual T cell subtypes in each NEXI-001 product were maintained in the peripheral blood of each patient at all time points measured, up to two months. These included sustained populations of T stem-cell-like memory and T central memory subtypes.

Early results from this Phase 1/2 trial suggest that infusion of the NEXI-001 product is well-tolerated and capable of triggering early, robust and persistent cell-mediated immune responses, said Dr. Al Malki, the trials lead investigator and associate clinical professor in City of Hopes Department of Hematology & Hematopoietic Cell Transplantation. The initial data are encouraging, and we look forward to dosing more patients with longer follow-up in order to more fully characterize the clinical potential of this exciting new cell therapy.

Relapse after allo-HSCT is the leading cause of death in patients with AML and represents a significant challenge for treating physicians. There are no approved therapies, and current treatment options are limited. Donor lymphocyte infusions (DLIs) represent the current standard of care but are associated with modest Graft versus Leukemia (GvL) responses and high rates of life-threatening GvHD-associated toxicities. There is significant need for new cellular therapies with potential to enhance the benefits of GvL while decreasing the incidence of GvHD-related toxicities.

Han Myint, M.D., Chief Medical Officer at NexImmune, added, While still early in this trial, we believe the initial data reported, combined with the unique and consistent composition of each NEXI-001 product, may offer a cell therapy with potential to decouple the benefits of GvL from the toxicities associated with GvHD, which would be transformative for both allogeneic stem cell transplant patients and the physicians that provide care for them.

About the Phase 1/2 NEXI-001 Clinical TrialThe first clinical trial with NEXI-001 is a prospective, multi-center, open-label, single-arm, dose-escalating Phase 1/2 study that aims to enroll between 22 to 28 patients. The primary objective is to assess the safety and tolerability of a single infusion of NEXI-001 T cells in patients with AML who have either minimum residual disease (MRD) or relapsed disease after a human leukocyte antigen (HLA)-matched allo-HSCT. Secondary objectives include signals of immunologic responses and preliminary anti-tumor activity. Additional analysis will assess the in vivo persistence, proliferation, functionality and TCR repertoire of NEXI-001 T cells as measured in blood and bone marrow samples.

This study includes two phases. The initial Safety Evaluation Phase determines the safety and tolerability of a single infusion of NEXI-001 at escalating dose levels. In the second part of the study, the Dose Expansion Phase, investigators further define safety and will also evaluate the initial efficacy of NEXI-001 T cells at the dose established in the Safety Evaluation Phase. Once a Recommended Phase II Dose has been determined, safety, tolerability and initial clinical response will become the objectives of the expansion phase of the trial, which is expected to begin in [the first quarter] of 2021.

NEXI-001 products contain populations of CD8+ T cells directed against HLA 02.01-restricted peptides from the WT1, PRAME and Cyclin A1 antigens, each of which is commonly over-expressed on AML blasts and leukemic stem cells. Each NEXI-001 product is composed of T cell memory subtypes that combine anti-tumor potency with long-term persistence. Of significance to this Phase 1/2 trial, each patient-specific experimental cell therapy product also contains very low proportions of T cell subtypes with potential to cause GvHD-related toxicities.

About NexImmuneNexImmune is a clinical-stage biotechnology company developing unique approaches to T cell immunotherapies based on its proprietary Artificial Immune Modulation (AIM) technology. The AIM technology is designed to generate a targeted T cell-mediated immune response and is initially being developed as a cell therapy for the treatment of hematologic malignancies. AIM nanoparticles act as synthetic dendritic cells to deliver immune-specific signals to targeted T cells and can direct the activation or suppression of cell-mediated immunity. In cancer, AIM-expanded T cells have demonstrated best-in-class anti-tumor properties as characterized by in vitro analysis, including a unique combination of anti-tumor potency, antigen target-specific killing, and long-term T cell persistence. The modular design of the AIM platform enables rapid expansion across multiple therapeutic areas, with both cell therapy and injectable products.

NexImmunes two lead T cell therapy programs, NEXI-001 and NEXI-002, are in Phase 1/2 clinical trials for the treatment of relapsed AML after allo-HSCT and multiple myeloma refractory to at least three prior lines of therapy, respectively. The Companys pipeline also has additional preclinical programs, including cell therapy and injectable product candidates for the treatment of solid tumors, autoimmune disorders and infectious diseases.

For more information, visit http://www.neximmune.com.

Media Contact:Mike BeyerSam Brown Inc. Healthcare Communications312-961-2502mikebeyer@sambrown.com

Investor Contact:Chad RubinSolebury Trout+1-646-378-2947crubin@soleburytrout.com

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Preliminary Results from NexImmune's Phase 1/2 Trial of NEXI-001 in AML Presented at 62nd ASH Annual Meeting and Exposition - GlobeNewswire

Were all familiar with the usual culprits that lead to skin aging, like not wearing a daily SPF, smoking, lack of hydration, genetics, stress, etc. But in the realm of internal and external factors that can zap your skin of its youthful bounce and glow, theres one important factor that isnt discussed nearly enough: inflammation.

While you might think of this condition only as it relates to a sprained ankle or a particularly aggressive zit, inflammation actually touches our daily lives in a multitude of ways. Its the result of those well-known aging factors (again, like stress and UV rays), but its not always a singular response, like redness or irritation. Says board-certified dermatologist Dr. Joshua Zeichner, Inflammation leads to free-radical damage in the skin, activation of matrix metalloproteinases, and [recruitment of] inflammatory blood cells. Collectively, this leads to damage to skin cells themselves along with destruction of supporting tissue like collagen and elastin. This explains why chronic inflammation can lead to weakening of the skin, premature wrinkling, and sagging.

Brands are starting to take note of how inflammation plays a central role in the aging process, particularly as it relates to the look and feel of our skin, and have dubbed this sequence of events as inflammaging. The beauty industry loves a trendy marketing term, sure, but in this case, there is some real data to back it up.

As Amir Nobakht, MD, MBA, and co-founder of Heraux, explains, Inflammation is supposed to be a temporary response to stress, activating stem cells to regenerate the skin after stress and injuries. However, if inflammation persists, the increased burden on stem cells accelerates the aging process as they are constantly in overdrive. This link between chronic inflammation and aging is referred to as inflammaging.

Together with his business partner Ben Van Handel, PhD, and a stem cell biologist at the University of Southern California, they founded their brand Heraux (which consists of a singular targeted serum with their proprietary molecule, HX-1) to address the signs and symptoms of this detrimental process and modulate the inflammatory pathway in the skin. Full disclosure: This editor has used their serum for as long as its been available, with no plans to stop anytime soon.

So why is this inflammation issue notable if you already know that things like smoking and tanning are bad for you? Well, unfortunately, inflammation is a rather stealthy foe, which can pop up in your skin without any visible indication that its happening. Dr. Nobakht emphasizes, Once [inflammation] is visible on the skin, that indicates a more severe response. This can include redness, rough texture, irritation, and even a burning sensation (think post-sunburn). Again, your skin is experiencing inflammation by its very nature as a barrier between the external and internal in our body. Inflammaging occurs when your skins ability to buffer inflammation is exceeded by the stressors present.

Essentially, the aging process is a slow, silent onethis we knowbut is exacerbated and accelerated by all the choices we make and the inflammatory responses they generate. Once your skin has weathered years and years of this type of inflammation, your defenses are weakened, and those signs of aging, like fine lines, hyperpigmentation, and sagging, inevitably appear.

As bleak as this may sound, there are things you can do to help slow the overall inflammaging progression and prevent premature signs of skin aging. Dr. Zeichner recommends a healthy lifestyle with a balanced diet and plenty of exercise to start, followed by a skin-care routine that incorporates daily sunscreen, gentle cleansers, antioxidant-rich products (think of antioxidants like fire extinguishers that put out inflammation caused by free radicals), a generous helping of moisturizer (particularly at night), and products that promote collagen production like retinoids and bakuchiol.

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How to Minimize Inflammation and Prevent Your Skin from Inflammaging - Coveteur

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

Skincare tips: Quit smoking as it can lead to premature ageing of skin

Rough-textured appearance, wrinkling and loss of elasticity are signs of ageing of skin. However, age and skin-ageing processes have been considered complex even with different factors. The conventional ageing mostly depends upon the individual genes, proteins, and other intrinsic in isolation. But, the processes of ageing involves interaction of physical, biological, psychological, social and cultural aspects as well. Ageing is alsoaffected by personal habits, diet and living environments beside medical issues. The effects of physical exercise, drugs, vitamins, hormones and antioxidants may have an impact on longevity. Skin is the hurdle that sets apart the body from the outer environment. Besides protecting the body from water loss and infections, it has an important cosmetic role.

Exposure to sunlight is the one of the biggest culprit in ageing skin. Over time, the sun's (UV) ultraviolet light damages certain fibers produced in the skin called elastin. The breakdown of elastin fibers causes the sking to stretch, sag, and lose its ability to restore back after stretching.

There are few ways which can help you slowdown ageing of skin. Here are a few of them:

1. Try drinking 2-3 liters of water per day. Hydrating keeps one's skin looking young, bright and glowing.

2. Exercising regularly decreases the chance for persistent disease, depression and cognitive decline, and can keep your skin looking younger.

3. Use fish oils. These supplements are rich in the essential omega-3 fatty acids EPA and DHA and enhance cardiovascular, vision health; strengthen skin, hair, and nails, and memory skills.

4. Glutathione is the master antioxidant in the body and also known for one of the most powerful supplements for slowing down the ageing process.

5. Alpha Lipoic Acid (ALA) is a potent, versatile antioxidant that helps to fend off inflammation, balances blood sugar and protect skin collagen of one's skin.

6. Stop smoking, it greatly speeds up your skin ages. It causes wrinkles and a dull, sallow complexion.

7. Avoid using alcohol. It is bad for the skin. It dehydrates the skin and with time, damages the skin.

8. Regular exercise can improve circulation and boost the immune system. This may give the skin a more-youthful appearance.

9. Apply a facial moisturiser on a daily basis. Moisturiser keeps water in our skin, giving it a more youthful appearance.

10. SC (Stem cell) transplantation is a promising therapy for the treatment of skin aging. Adipose tissue transplantation could improve skin quality and increase skin volume that adipose-derived stem cells (ADSCs) contribute to the regeneration of skin during ageing.

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(Dr. Ajay Rana is Dermatologist and Aesthetic Physician, Founder and Director of ILAMED)

Disclaimer: The opinions expressed within this article are the personal opinions of the author. NDTV is not responsible for the accuracy, completeness, suitability, or validity of any information on this article. All information is provided on an as-is basis. The information, facts or opinions appearing in the article do not reflect the views of NDTV and NDTV does not assume any responsibility or liability for the same.

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Skincare Tips: Expert Shares Facts About Ageing Of Skin That You Must Know - NDTV Doctor

Aging has implications for a wide range of diseases. Researchers have been looking for ways to halt the aging process for millennia, but such methods remain elusive. Scientists at Harvard Medical School have now offered a glimmer of hope that the aging clock in the eye could be reversedat least in animals.

By reprogramming the expression of three genes, the Harvard team successfully triggered mature nerve cells in mice eyes to adopt a youthful state. The method reversed glaucoma in the mice and reversed age-related vision loss in elderly mice, according to results published in Nature.

If further studies prove out the concept, they could pave the way for therapies that employ the same approach to repair damagein other organs and possibly treat age-related diseases in humans, the team said.

The researchers focused on the Yamanaka factors, which are four transcription factorsOct4, Sox2, Klf4 and c-Myc. In a Nobel Prize-winning discovery, Shinya Yamanaka found that the factors can change the epigenomehow genes are turned on or offand can thereby transform mature cellsback to a stem cell-like state. It has been hypothesized that changes to the epigenome drive cell aging, especially a process called DNA methylation, by which methyl groups are tagged onto DNA.

Past researches have tried to use the four Yamanaka factorsto turn back the age clock in living animals, but doing so caused cells to adopt unwanted new identities and induced tumor growth.

RELATED:Restoring eyesight with genetically engineered stem cells

To test whether the approach works in living animals, the scientists used adeno-associated virus to deliver the three genes into the retina of mice with optic nerve injuries. The treatment led to a two-fold increase in the number of retinal ganglion cells, which are neurons responsible for receiving and transmitting visual information. Further analysis showed that the injury accelerated DNA methylation age, while the gene cocktail counteracted that effect.

Next the scientists tested whether the gene therapy could also work in disease settings. In a mouse model of induced glaucomawhich is a leading cause of age-related blindness in peoplethe treatment increased nerve cell electrical activity and the animals visual acuity.

But can the therapy also restore vision loss caused by natural aging? In elderly, 12-month-old mice, the gene therapy also restored ganglion cells electrical activity as well as visual acuity, the team reported.

By comparing cells from the treated micewith retinal ganglion cells from young, 5-month-old mice, the researchers found that mRNA levels of 464 genes were altered during aging, and the gene therapy reversed 90% of those changes. The scientists also noticed reversed patterns of DNA methylation, which suggests that DNA methylation is not just the marker but rather the driver behind aging.

What this tells us is the clock doesn't just represent timeit is time. If you wind the hands of the clock back, time also goes backward, the studys senior author, David Sinclair, explained in a statement.

The study marks the first time that glaucoma-induced vision loss was reversednot just slowedin living animals, according to the team.

RELATED:Reprogrammed skin cells restore sight in mouse models of retinal disease

Other researchers are also studying regenerative approaches to treating eye diseases. A research group at the Centre for Genomic Regulation in Barcelona just showed that by modifying mesenchymal stem cells to express chemokine receptors Ccr5 and Cxcr6, retinal tissue could be saved from degeneration.

The idea of reversing age-related decline in humans by epigenetic reprogramming with a gene therapy is exciting, Sinclair said. The Harvard researchers intend to do more animal work that could allow them to start clinical trials in people with glaucoma in about two years.

Our study demonstrates that it's possible to safely reverse the age of complex tissues such as the retina and restore its youthful biological function, Sinclair said. If affirmed through further studies, these findings could be transformative for the care of age-related vision diseases like glaucoma and to the fields of biology and medical therapeutics for disease at large.

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Reversing vision loss by turning back the aging clock - FierceBiotech