Stem Cell Clinic

Stem cell therapy: why we need to be suspicious about cure-all claims – The Irish Times

If you were to read many of the adverts for stem cell therapy that you can find online, you would be forgiven for believing that stem cell therapy is nothing short of a panacea. It is, according to those ads, able to improve all sorts of conditions, from knee pain and osteoarthritis, hair loss to heart disease, diabetes and even autism.

Theres just one problem theres little science behind many of the claims.

Stem cells are only approved for use in treating certain cancers and blood disorders, yet a search for the term on Facebook or Google will return details of a large number of clinics offering treatments for many other conditions.

The harsh reality is that while there is a lot of promising research being undertaken in this area, nobody should be parting with large sums of money for what may be currently no more than snake oil treatments, according to Noel Caplice, who is professor of cardiovascular sciences in the department of medicine at University College Cork and a consultant cardiologist.

Caplice, who has more than 20 years experience monitoring stem cell research as part of his studies into heart disease, told The Irish Times that we should all be suspicious about the range of different ailments clinics are willing to treat with stem cells.

There should be red lights flashing and alarm bells ringing. No therapy treats everything from Parkinsons disease to multiple sclerosis to heart disease to knee pain thats idiotic. Medicine just doesnt work like that.

True stem cell therapy is extremely complex because you have to refine the type of cell youre going to give to the organ it will be used in, and there are different challenges in different organs. Legitimate scientists are working on these things, but they are not there yet. Its an incredibly difficult area of research.

Stem cells have long been considered a great hope of medicine. They are the bodys building blocks, the cells from which other types of cells develop. Under the right conditions they can be encouraged to become any other type of cell found in the body, such as blood cells, brain cells, heart muscle cells and so on.

At its simplest, stem cell therapy involves cultivating stem cells in the lab, guiding them to grow into specific types of other cells, and then injecting those healthy cells into diseased parts of the body where in certain circumstances they have been shown to help the bodys own cells to fight disease.

This effect was first shown around 30 years ago in experiments on mice. However, things have not been all plain sailing since then.

The initial promise of stem cells has not been fulfilled, and whats happened in the meantime is that commercial clinics offering treatments have gotten ahead of the science, said Caplice.

The first trials in mice showed incredible regeneration, but their progress turned out not to be so straightforward. When the initial trials were replicated, the researchers couldnt reproduce the same early data.

While research is ongoing and there have been a few significant breakthroughs using stem cells, notably in the case of combined stem cell and gene therapy for thalassemia and leukaemia, that has not stopped unscrupulous clinics from marketing all sorts of treatments under the banner of stem cell therapy.

In the private world anything goes. There are people spinning this therapy for multiple sclerosis, Parkinsons, solid organ deterioration a whole range of problems. Ten years ago there was even a boat operating off the west Cork coast that was treating people for multiple sclerosis using stem cells. This has been going on for decades in this parallel world, and its mostly driven by money, Caplice said.

According to Frank Barry, professor of cellular therapy at the regenerative medicine institute with NUI Galway, a negative side effect of the off-label use of stem cells is that it makes it harder for researchers to raise money for research.

It damages our reputation to have people doing this. We all get painted with the same brush, and it makes it much harder to raise money. When these maverick clinics are exposed for their bad practices, there is a blow-back effect on us even though were completely unconnected, he said.

The sad thing is that there are genuinely quite exciting applications of stem cell therapy that will be possible in the future. All of these are undergoing scientifically-designed clinical trials that are carefully done, carefully managed, are placebo-controlled, double blind the works. Some of these trials are going quite well and suggest that the outcome will be good.

The biopharmaceutical company Takeda Ireland, for example, is currently developing a treatment for inflammatory bowel disease using the results of a trial that was conducted into stem cells.

Thats a dreadful condition that blights peoples lives. This is a new treatment so thats very exciting. That project achieved market authorisation because of careful work done over many years in high quality clinical trials, said Barry.

My own work is in the treatment of arthritis with stem cell therapy, and thats also going well. Were in the middle of a big trial thats been running in a number of clinical sites around Europe, and we think that when its finished itll be positive.

Running trials like these takes a lot of time and a lot of money. In the meantime bad actors are stepping into the gap that exists between promising early results and actual rigorous and robust science.

The harsh reality is that you cant recommend that a patient has stem cell therapy for anything that isnt directly authorised. If someone does that now theyre getting it off-label, so to speak, and basically theyre taking their chances, said Barry.

I can understand why someone might want to do that, but its not authorised. I would hold out a great deal of hope that when all the work is done there will be strong proof supporting this kind of treatment. But at the moment you can spend a huge amount of money essentially for nothing because there isnt the evidence to support treatment.

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Stem cell therapy: why we need to be suspicious about cure-all claims - The Irish Times

Over $8M in 2020 Stem Cell Funding Awards Continue to Fuel Marylands Leading Cell Therapy Industry – BioBuzz

The Maryland Stem Cell Research Commission (The Commission) recently announced over $7M in Maryland Stem Cell Research Fund (MSRCF) grant awards for its second round of 2020 MSCRF fund recipients. The MSCRF, which is a program of the Maryland Technology Development Corporation (TEDCO), has awarded $157M in funding to BioHealth Capital Region (BHCR) companies seeking to accelerate stem cell research, therapies and commercialization of products since 2007.

The $7M in new funding follows MSCRFs announcement in September 2019 of over $1.3M in grants for the first cohort of 2020 recipients, bringing the total 2020 MSCRF award tally to approximately $8.3M for the year. The financial awards are delivered across a wide range of areas, including clinical, commercialization, validation, launch, discovery, and post-doctoral fellowships. The first cohort of funding included three commercialization and two validation awards; the second, larger recipient pool included one clinical, one commercialization, one validation, four launches, 11 discovery, and five post-doctoral awards.

Notable BHCR MSCRF recipients included:

Dr. Luis Garza of Johns Hopkins University (JHU) received a clinical grant to support clinical trials for his autologous volar fibroblast injection into the stump site of amputees. The trials are exploring ways to make the skin where a prosthetic limb meets the stump site tougher and less irritable to the wearer. Skin irritation is a major issue for those with prosthetic limbs and is often a cause for individuals to stop wearing their prosthesis.

Vita Therapeutics, a company that spun out of JHU, was awarded a 300K MSCRF grant to support the commercialization of the companys satellite stem cell therapy for limb-girdle Muscular Dystrophy. According to the National Organization for Rare Disorders (NORD), Limb-girdle muscular dystrophies (LGMD) are a group of rare progressive genetic disorders that are characterized by wasting (atrophy) and weakness of the voluntary muscles of the hip and shoulder areas (limb-girdle area). Vita Therapeutics is led by CEO Douglass Falk, who is a JHU alum.

Jamie Niland, VP of Baltimore, Marylands Neoprogen Inc. received part of $892,080K in funding that was part of MSCRFs first 2020 grant round. Jamie is the son of Bill Niland, Neoprogens current CEO and the former leader of Baltimore, Maryland life science community anchor Harpoon Medical, which was acquired by Edwards Scientific in 2017. The award was for Neoprogens neonatal cardiac stem cells for the heart tissue regeneration program.

Dr. Brian Pollok of Rockville, Marylands Propagenix, Inc., was also the recipient of a commercialization award for his Apical Surface-Outward (ASO) airway organoids, which is a potential novel cell system for drug discovery and personalized medicine. Propagenix develops innovative new technologies that address unmet needs in epithelial cell biologyfor applications in life science research as well as in precision diagnostics, and next-generation therapeutics such as immune-oncology, tissue engineering, and regenerative medicine, according to the companys website.

In addition, Dr. Ines Silva, R&D Manager of REPROCELL, USA received an MSCRF commercialization grant for its work on building a commercial neural cell bank from patient-derived induced pluripotent stem cells. REPROCELL was founded in Japan in 2003 and acquired BioServe in Beltsville, Maryland in 2014.

Dr. Sashank Reddy, the founder of JHU startup LifeSprout and Medical Director, Johns Hopkins Technology Ventures Johns Hopkins University, received a portion of the $1,334,462 distributed for launch grants in 2020. The grant will go to support the launch of regenerative cell therapies for soft tissue restoration. LifeSprout recently closed a $28.5M seed round.

Past MSCRF grant recipients include Frederick, Marylands RoosterBio, Inc. and Theradaptive, Inc., and Baltimore, Marylands Gemstone Biotherapeutics and Domicell, Inc., among others.

TEDCOs MSRF program continues to lend its deep support and ample funding to build and grow Marylands burgeoning and exciting regenerative medicine industry. Well be keeping a close eye on these companies as they grow and make future contributions to the thriving BHCR biocluster.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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Over $8M in 2020 Stem Cell Funding Awards Continue to Fuel Marylands Leading Cell Therapy Industry - BioBuzz

Should You Delay Cancer Treatment Because of COVID-19? Study Says Most Treatments Dont Worsen Coronavirus Infection – On Cancer – Memorial Sloan…

Summary

A review of 423 patients treated at MSK finds that most people with cancer dont fare any worse if they get COVID-19 than other people who are hospitalized for that infection.

In the early days of the COVID-19 pandemic, many doctors worried that people undergoing treatment for cancer would do particularly poorly if they became infected with the virus that causes the disease. Thats because treatments for cancer, especially chemotherapy, can lower a persons immune defenses and put them at higher risk for all kinds of infections.

But according to a new study from Memorial Sloan Kettering published June 24 in Nature Medicine, most people in active cancer treatment dont fare any worse if they get COVID-19 than other people who are hospitalized with the infection. Further research is needed to look at the effects of certain drugs mainly immunotherapies called checkpoint inhibitors, which did seem to make COVID-19 worse. But the researchers say their findings suggest that no one should delay cancer treatment because of concerns about the virus.

If youre an oncologist and youre trying to figure out whether to give patients chemotherapy, or if youre a patient who needs treatment, these findings should be very reassuring, says infectious disease specialist Ying Taur, one of the studys two senior authors.

Infectious disease expert Ying Taur has cared for many MSK patients who were hospitalized with COVID-19.

The study looked at 423 MSK patients diagnosed with COVID-19 between March 10 and April 7, 2020. Overall, 40% were hospitalized for COVID-19, and 20% developed severe respiratory illness. About 9% had to be placed on a mechanical ventilator, and 12% died. The investigators found that patients taking immunotherapy drugs called immune checkpoint inhibitors were more likely to develop severe disease and require hospitalization. But other cancer treatments, including chemotherapy and surgery, did not contribute to worse outcomes.

The big message now is clear: People should stay vigilant but not stop or postpone checkpoint immunotherapy or any other cancer treatment.

Factors that did make COVID-19 worse were the same as those seen in studies of people who didnt have cancer. We found that being older, as well as preexisting conditions like heart disease and diabetes, are all drivers of severe COVID-19 illness, says MSK Chief Medical Epidemiologist Mini Kamboj, the studys other senior author. This wasnt surprisingbecause these connections are well established.

Although the study wasnt large enough to make determinations about every treatment and every cancer type, patterns did emerge. Dr. Taur says there was initially great concern about people receiving high doses of chemotherapy for leukemia, especially those who had recently undergone bone marrow or stem cell transplants. Thats because transplants require a persons entire immune system to be wiped out with chemotherapy before they receive new blood cells, leaving them susceptible to all kinds of infections.

Surprisingly, though, Dr. Taur cared for recent transplant recipients who were infected with COVID-19 but didnt have any symptoms. If you think about it more, it makes sense, he says. Most of the complications seen in people with COVID-19 seem to be caused by the bodys immune response to the virus.

On the other hand, immunotherapy drugs called checkpoint inhibitors work by freeing up the immune system to attack cancer. Patients receiving these agents may develop a more robust reaction to the virus that causes COVID-19. This may explain why this study observed higher rates of complications in people with COVID-19 infection who were treated with checkpoint inhibitors.

Even with immune checkpoint inhibitors, though, these findings should not affect whether patients get treated. Everyone who needs these drugs should still receive them, Dr. Kamboj says. Its just important for doctors to be extra vigilant about testing and monitoring for the virus and for people with cancer to take extra precautions to avoid infection.

A study published in May 2020 by MSK immunotherapy expert Matthew Hellmann focused exclusively on people with lung cancer who got COVID-19. The researchers didnt find the same risks from immune checkpoint drugs as this Nature Medicine study. But that study included data on far fewer patients treated at MSK, which could explain the difference.

Dr. Kamboj notes that one aspect of this research that sets it apart from other studies is that it included at least 30 days of follow-up after a COVID-19 diagnosis. Also, it reported severe respiratory illness as a main outcome rather than death.

Having that follow-up time is something that a lot of other studies have not included because everyone is in a rush to get their data out. In addition, reporting death rates can overestimate infection-related mortality, especially in the early phase of an epidemic, Dr. Kamboj says. Also, the clinical spectrum and course of this disease is still not fully understood, especially in people with cancer. We wanted to give patients enough time to recover and make sure they didnt need to be readmitted to the hospital.

Even with immune checkpoint inhibitors, though, these findings should not affect whether patients get treated. Everyone who needs these drugs should still receive them.

She adds that another strength of the study is that patient outcomes were not affected by constraints caused by a lack of space or supplies even though MSK is in the heart of the COVID-19 epicenter in New York City, where other hospitals faced overcrowding and other issues. This gave researchers a true picture of how cancer patients fare with COVID-19. We saw a surge during the peak of the epidemic in New York, but everyone got the care they needed, Dr. Kamboj explains. We had enough ventilators for everyone who needed them. We never had to make decisions about who to admit to intensive care because of a lack of critical equipment.

Drs. Taur and Kamboj agree that this is just one of many studies that will need to be done on the connections between cancer and COVID-19. We still need to find out more. We need to look at the connections between COVID-19 and particular types of cancer as well as outcomes related to specific chemotherapy drugs, Dr. Taur concludes. But the big message now is clear: People should stay vigilant but not stop or postpone checkpoint immunotherapy or any other cancer treatment.

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Should You Delay Cancer Treatment Because of COVID-19? Study Says Most Treatments Dont Worsen Coronavirus Infection - On Cancer - Memorial Sloan...

TP53, KMT2D Abnormalities Linked With Poor Prognosis in MCL – Targeted Oncology

Disruption of the TP53 gene and mutation of the KMT2D gene are predictive of poor outcomes in patients with mantle cell lymphoma (MCL) who are receiving high-dose therapy, according to a new study.

The findings, which build upon growing knowledge of the genetics of MCL, can be used to better classify patients into risk categories, the investigators said. The study was published in the journal Haematologica.1

Corresponding author Simone Ferrero, MD, of the University of Torino, in Italy, noted that the current treatment paradigm for patients with MCLcytarabine-based chemotherapy followed by autologous stem cell transplantation (ASCT)has led to dramatic advancements in the outcomes of patients who are young and healthy enough for the therapy. However, Ferrero said as many as one-quarter of those patients will experience early treatment failure.

So far, the best tool clinicians have had to identify patients at high risk of relapse has been the MCL international prognostic index (MIPI), and the Ki-67 proliferation index. The combination of the 2 is known as the MIPI-c score. Although the tool is of value, Ferrero and colleagues asserted that the resulting scores lack the precision necessary to develop tailored schedules specifically for high-risk patients.

In an effort to better elucidate the factors associated with a high risk of failure, the investigators used samples from the phase III FIL-MCL0208 trial, which is a prospective, open-label, multicenter study designed to evaluate lenalidomide (Revlimid) as a maintenance therapy versus observation in patients in MCL remission following high-dose chemotherapy including rituximab (Rituxan) followed by ASCT (NCT02354313).

Ferrero and colleagues performed targeted resequencing and DNA profiling on purified tumor samples of the patients in the study. Out of 300 patients enrolled in the study, samples from 186 patients were able to be evaluated for genetic mutations and abnormalities in copy numbers.

The analysis confirmed earlier reports2,3 that TP53 disruption is a significant prognostic factor. After 4 years, patients with mutations or deletions of TP53 had lower progression-free survival (PFS) and overall survival (OS) rates compared with patients without the disruptions.

However, the authors broke new ground by identifying KMT2D as another important genetic factor. In wild-type cases, those with KMT2D mutations had PFS rates of just 33.2%, versus 63.7% in those without the mutation after 4 years (P <.001). Overall survival was similarly affected; the 4-year OS rate among patients with KMT2D mutations was 62.3% versus 86.8% among those without the mutation (P = .002).

In the FIL-MCL0208 trial, KMT2D mutations emerged as a novel biomarker heralding chemo-immunotherapy failure, with a predictive value similar to that of TP53 aberrations, Ferrero and colleagues wrote.

The authors then used their findings to create a new scoring system to identify patients at the highest risk.

The independent adverse prognostic value of TP53 and KMT2D aberrations prompted us to integrate the molecular results into the MIPI-c, aiming at further improving its ability to discriminate high-risk patients, the authors said.

The model begins with MIPI-c score; those with low or intermediate risk scores under MIPI-c were given 0 points in the new model, and those placed in the high-risk category by the MIPI-c model were given one point. In addition, patients with TP53 disruptions were given 2 additional points, as were those with the KMT2D mutation. In this new scoring system, which the investigators dubbed MIPI-g, patients with a score of 0 were deemed low risk, patients with scores of 1 to 2 were deemed intermediate risk, and patients with scores of 3 or higher were categorized as high risk.

When investigators performed PFS and OS calculations based on their risk categories, they found PFS rates varied dramatically among the groups, from 72.0% in the low-risk group to 11.5% in the high-risk group after 4 years (P <.0001). Four-year OS rates similarly dropped from 94.5% in the low-risk group to 44.9% (P <.0001). Among patients in the intermediate group, the 4-year PFS rate was 42.2% and the OS rate was 65.8%.

In the Nordic validation series, patients with KMT2D mutations showed similar worse outcomes compared with wild-type patients (median OS, 8.4 vs 12.7 years). Among patients with TP53 mutations, the median OS was 2.0 years compared with 12.7 years for patients with wild-type TP53. The validation series also showed similar 4-year OS rates by risk groups: 91.3% for low-risk patients, 72.2% for intermediate risk, and 15.4% for high risk.

Among the studys limitations, the authors noted that their analysis was performed only on CD19-positive bone marrow cells. The investigators also said they do not yet have sufficient randomization data to know whether and to what extent lenalidomide maintenance affected the patients with these mutations within the broader FIL-MCL0208 trial. However, they said it is unlikely that full data will be able to offer clear takeaways, since only 27 patients with the TP53/KMT2D mutations were finally randomized in the study, due to a high rate of progressive disease among these patients. Of those 27, only 9 were started on lenalidomide maintenance.

In their conclusion, Ferrero and colleagues said that the ability to distinguish the highest-risk patients could be used by clinicians to identify high-risk patients for novel therapeutic approaches.

As in other lymphoid disorders, novel non-chemotherapeutic strategies specifically designed for [high-risk] patients need to be investigated in MCL, the authors said. Besides the approved drugs lenalidomide and ibrutinib [Imbruvica], new molecules such as the BCL-2 inhibitor venetoclax [Venclexta] might be very promising for these chemorefractory patients, especially for TP53 disrupted cases.

References:

1. Ferrero S, Rossi D, Rinaldi A, et al. KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study. Haematologica. 2020;105(6):1604-1612. doi:10.3324/haematol.2018.214056

2. Nordstrm L, Sernbo S, Eden P, et al. SOX11 and TP53 add prognostic information to MIPI in a homogeneously treated cohort of mantle cell lymphoma--a Nordic Lymphoma Group study. Br J Haematol. 2014;166(1):98-108. doi:10.1111/bjh.12854

3. Halldrsdttir AM, Lundin A, Murray F, et al. Impact of TP53 mutation and 17p deletion in mantle cell lymphoma. Leukemia. 2011;25(12):1904-1908. doi:10.1038/leu.2011.162

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TP53, KMT2D Abnormalities Linked With Poor Prognosis in MCL - Targeted Oncology

Karyopharm Announces Publication of XPOVIO (Selinexor) Phase 2b SADAL Study Results in The Lancet Haematology – GlobeNewswire

June 24, 2020 07:00 ET | Source: Karyopharm Therapeutics Inc.

NEWTON, Mass., June 24, 2020 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an innovation-driven pharmaceutical company, today announced that the results of the Phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study evaluating XPOVIO in patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) were published online in The Lancet Haematology. The SADAL study evaluated selinexor, the Companys first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound for the treatment of adult patients with RR DLBCL, not otherwise specified, who have received at least two prior therapies.

The clinical outcomes for patients with heavily pretreated relapsed or refractory DLBCL are typically very poor, and hence results from the multinational Phase 2b SADAL study are noteworthy, said Prof Nagesh Kalakonda, University of Liverpool, lead author of the manuscript. In this population, single-agent oral XPOVIO (selinexor) demonstrated an overall response rate of 28%, including a complete response rate of 12%. Responses were seen in all subgroups regardless of age, gender, prior therapy, DLBCL subtype or prior stem cell transplant therapy. Importantly, patient responses were durable with a median duration of response of 9.3 months (23.0 months for patients who achieved a complete response). Finally, responses were associated with longer survival, underscoring the potential of oral XPO1 inhibition as an oral, non-chemotherapeutic option for patients with RR DLBCL.

These positive data further reinforce our strong belief that oral XPOVIO offers patients an important new treatment option, especially considering the patient population studied in SADAL had an expected median survival of less than six months. Furthermore, treatment with XPOVIO demonstrated deep and durable responses with a safety profile qualitatively similar to previous clinical studies with XPOVIO, said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. We are proud to see these published clinical results and are excited to now commercialize XPOVIO in our second cancer indication on behalf of the patients and families who are desperately in need of new treatment options.

The U.S. Food and Drug Administration (FDA) approved XPOVIO on June 22, 2020 for the treatment of adult patients with RR DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication was approved based on response rate under the FDAs Accelerated Approval Program, which was developed to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). A Marketing Authorization Application for selinexor for RR DLBCL is planned for submission to the European Medicines Agency in 2021.

The Phase 2b SADAL Study Results

The published results are based on the multi-center, single-arm Phase 2b SADAL study (NCT02227251), which evaluated 127 patients (median of 2 prior treatment regimens) with RR DLBCL. Patients received a fixed 60 mg dose of XPOVIO given orally twice weekly for a four-week cycle. Patients with germinal center B-cell (GCB) or non-GCB subtypes of DLBCL were included in enrollment.

The SADAL study met its primary endpoint of overall response rate (ORR) with an ORR of 28%, including 15 complete responses (CRs) and 21 partial responses (PRs). An additional 11 patients experienced stable disease (SD) for a disease control rate of 37.0%. The ORR in the 59 patients with the GCB-subtype was 34% and the ORR in the 63 patients with the non-GCB subtype was 21%. In addition, there were 5 patients enrolled whose subtype was unclassified and 1 of these patients achieved a CR while 2 of these patients achieved a partial response (PR).

Key secondary endpoints included a median duration of response (DOR) in the responding patients of 9.3 months and median overall survival (OS) across the entire study population of 9.1 months. Median OS has not yet been reached in patients who achieved either a CR or PR. In patients who had stable disease, the median OS was 18.3 months. Patients whose disease progressed or had no response to XPOVIO had a median OS of 4.3 months, which is consistent with the expected poor prognosis for patients who have RR DLBCL and have been previously treated with two or more lines of therapy.

All 127 patients were included in the safety analyses. The most common treatment-related adverse events (AEs) were cytopenias along with gastrointestinal and constitutional symptoms and were generally reversible and managed with dose modifications and/or standard supportive care. The most common non-hematologic AEs were nausea (58%), fatigue (47%), and decreased appetite (37%) and were mostly Grade 1 and 2 events. As expected, the most common Grade 3 and 4 AEs were thrombocytopenia (46%), neutropenia (24%) and anemia (22%) and were generally not associated with clinical sequelae.

The patient population described in this publication includes data from 127 patients in the SADAL study while the FDA approved label includes data from seven additional patients or 134 patients total. As such, there are minor differences in the efficacy and safety percentages between the two sources.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm submitted a supplemental New Drug Application (sNDA) to the FDA requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy based on the positive results from the Phase 3 BOSTON study which evaluated selinexor in combination with Velcade (bortezomib) and low-dose dexamethasone. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharms clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at http://www.clinicaltrials.gov.

For more information about Karyopharms products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326 Email: medicalinformation@karyopharm.com

IMPORTANT SAFETY INFORMATION

Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.

Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).

Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.

Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.

Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.

Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.

Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

Monitor for signs and symptoms of infection, and evaluate and treat promptly.

Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.

Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.

Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

ADVERSE REACTIONS

The most common adverse reactions (ARs) in 20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

The most common ARs, excluding laboratory abnormalities, in 20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in 15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in 5% were thrombocytopenia, lymphopenia, and neutropenia.

In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in 4% of patients included fatigue, nausea, and thrombocytopenia.

In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.

USE IN SPECIFIC POPULATIONS

In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients 75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

Please see full Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

About Karyopharm Therapeutics

Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is an innovation-driven pharmaceutical company dedicated to the discovery, development, and commercialization of novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major diseases. Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyopharms lead compound, XPOVIO (selinexor), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain viruses and wound-healing. Karyopharm has several investigational programs in clinical or preclinical development. For more information, please visit http://www.karyopharm.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharms beliefs regarding XPOVIOs ability to treat patients with relapsed or refractory diffuse large B-cell lymphoma and expectations related to other XPOVIO regulatory submissions. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that any positive developments in the development or commercialization of Karyopharms drug candidate portfolio will result in stock price appreciation. Managements expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the risk that the COVID-19 pandemic could disrupt Karyopharms business more severely than it currently anticipates, including by reducing sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharms drug candidates that receive regulatory approval; the ability to retain regulatory approval of XPOVIO or any of Karyopharms drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharms competitors for indications in which Karyopharm is currently developing its drug candidates; and Karyopharms ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks are described under the caption "Risk Factors" in Karyopharms Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, which was filed with the Securities and Exchange Commission (SEC) on May 5, 2020, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Velcade is a registered trademark of Takeda Pharmaceutical Company Limited.

Contacts:

Investors: Karyopharm Therapeutics Inc. Ian Karp, Vice President, Investor and Public Relations 857-297-2241 | ikarp@karyopharm.com

Media:

FTI Consulting Simona Kormanikova or Robert Stanislaro 212-850-5600 |Simona.Kormanikova@fticonsulting.com or robert.stanislaro@fticonsulting.com

More:
Karyopharm Announces Publication of XPOVIO (Selinexor) Phase 2b SADAL Study Results in The Lancet Haematology - GlobeNewswire

Stem Cell Therapy Market 2020: Industry Growth, Competitive Analysis, Future Prospects and Forecast 2025 – 3rd Watch News

Stem Cell Therapy market report provides a complete assessment of this industry sector through a thorough analysis of various market segments. This study summarizes industry scenarios for current market position and industry size based on size and revenue share. Stem Cell Therapy market provides important information about the markets geographic environment and key organizations that define the markets competitive hierarchy.

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Read complete report with TOC at:https://www.adroitmarketresearch.com/industry-reports/stem-cell-therapy-market

Stem Cell Therapy Market report provides in-depth analysis and insights into developments impacting businesses and enterprises on global and regional level. The report covers the global Stem Cell Therapy Market performance in terms of revenue contribution from various segments and includes a detailed analysis of key trends, drivers, restraints, and opportunities influencing revenue growth of the global consumer electronics market. This report studies the global Stem Cell Therapy Market size, industry status and forecast, competition landscape and growth opportunity. This research report categorizes the market by companies, region, type and end-use industry.

Global Stem Cell Therapy market is segmented based by type, application and region.

Based on Type, the market has been segmented into:

Based on cell source, the market has been segmented into,

Adipose Tissue-Derived Mesenchymal SCs Bone Marrow-Derived Mesenchymal SCs Embryonic SCs Other Sources

Based on application, the market has been segmented into:

Based on therapeutic application, the market has been segmented into,

Musculoskeletal Disorders Wounds & Injuries Cardiovascular Diseases Gastrointestinal Diseases Immune System Diseases Other Applications

In terms of region, this research report covers almost all major regions of the world, such as North America, Europe, South America, the Middle East, and Africa and Asia Pacific. Europe and North America are expected to increase over the next few years. In Stem Cell Therapy market the Asia Pacific region are expected to grow significantly during the forecast period. The latest technologies and innovations are the most important characteristics of North America and the main reason the United States dominates the world market. The South American keyword market is also expected to grow in the near future.

The research study can answer the following Key questions: What are the prominent factors driving the Stem Cell Therapy Market across different regions? What will be the progress rate of the Stem Cell Therapy Market for the conjecture period 2020 2025? Who are the major vendors dominating the Stem Cell Therapy industry and what are their winning strategies? What are the challenges faced by the Stem Cell Therapy Market? What will be the market scope for the estimated period? What are the major trends shaping the expansion of the industry in the coming years?

Do You Have Any Query Or Specific Requirement? Ask to Our Industry Expert @https://www.adroitmarketresearch.com/contacts/enquiry-before-buying/691

About Us :

Adroit Market Research is an India-based business analytics and consulting company. Our target audience is a wide range of corporations, manufacturing companies, product/technology development institutions and industry associations that require understanding of a markets size, key trends, participants and future outlook of an industry. We intend to become our clients knowledge partner and provide them with valuable market insights to help create opportunities that increase their revenues. We follow a code Explore, Learn and Transform. At our core, we are curious people who love to identify and understand industry patterns, create an insightful study around our findings and churn out money-making roadmaps.

Contact Us :

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Stem Cell Therapy Market 2020: Industry Growth, Competitive Analysis, Future Prospects and Forecast 2025 - 3rd Watch News

Century Therapeutics Announces Acquisition of Empirica Therapeutics – Business Wire

PHILADELPHIA--(BUSINESS WIRE)--Century Therapeutics today announced its acquisition of Empirica Therapeutics to leverage its iPSC-derived allogeneic cell therapies against glioblastoma (GBM).

We are pleased to welcome the Empirica team to the Century family. Their deep expertise and unique capabilities will allow us to accelerate efforts to develop iPSC derived immune effector cell products designed to treat and potentially cure brain cancer, said Lalo Flores, PhD, Chief Executive Officer of Century Therapeutics. GBM is a particularly aggressive, often treatment-resistant form of adult brain cancer with an average survival time of under two years. Together, we are in a stronger position to develop potentially curative cell therapies for this devastating disease.

Empirica Therapeutics was founded by Dr. Sheila Singh, MD, PhD, Professor of Surgery and Biochemistry and chief pediatric neurosurgeon at McMaster Childrens Hospital, and Dr. Jason Moffat, PhD, Professor of Molecular Genetics at the University of Toronto and an expert in functional genomics and gene-editing platforms. The companys science is based on a powerful integrative multi-omics platform, combined with its unique patient-derived, therapy-adapted models of recurrent GBM, that has led to the discovery and validation of novel brain tumor targets. Empiricas cutting edge preclinical models of recurrent GBM, have demonstrated the potential of CAR-T cell therapy in GBM, as published in a May 2020 Cell Stem Cell paper.

Our team is excited to become part of Century Therapeutics, whose iPSC-derived allogeneic cell therapies show immense potential for treating solid as well as hematologic malignancies, said Dr. Singh. Dr. Singh served as Empiricas CEO after co-founding the company with Chief Scientific Officer Dr. Moffat. We look forward to combining our unique patient-based cancer models with Centurys platform to create promising treatments for the patients who need them most, Singh said.

Janelle Anderson, PhD, Chief Strategy Officer at Century Therapeutics, shepherded the deal forming the subsidiary, which will be known as Century Therapeutics Canada and based in Hamilton, Ontario. Financial terms of the deal have not been disclosed.

About Century Therapeutics

Century Therapeutics is harnessing the power of stem cells to develop curative cell therapy products for cancer that overcome the limitations of first-generation cell therapies. Our genetically engineered, universal iPSC-derived immune effector cell products (iNK, iT) are designed to specifically target hematologic and solid tumor cancers. Our commitment to developing off-the-shelf cell therapies will expand patient access and provides an unparalleled opportunity to advance the course of cancer care. Century was launched in 2019 by founding investor Versant Ventures in partnership with Fujifilm and Leaps by Bayer. For more information, please visit http://www.centurytx.com.

About Glioblastoma (GBM)

Glioblastoma (GBM) is one of the most common types of primary brain tumor in adults and is almost uniformly lethal, with less than 5% of patients living beyond five years. GBM has an incidence rate of 3 per 100,000 people annually in the United States of America. The standard of care for GBM consists of tumor resection following by chemotherapy and radiation. Despite aggressive multimodal treatment, almost all patients experience relapse 7-9 months post-diagnosis and median survival has not extended beyond 16-20 months over the past decade. Recent studies suggest that the primary GBM tumor evolves significantly during the course of therapy and presents itself as a much more aggressive tumor at the time of recurrence. The treatment-resistant nature of GBM to standard therapies provides compelling motivation for developing novel treatment approaches.

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Century Therapeutics Announces Acquisition of Empirica Therapeutics - Business Wire