Category Archives: Cell Medicine

For years, the American Society of Clinical Oncologys annual meeting has served as the main forum for advances in cancer immunotherapies like Merck & Co.s Keytruda and Bristol Myers Squibbs Opdivo.

While new data continue to emerge for those drugs and their competitors, this years conference was headlined by dramatic data for another type of cancer medicine from AstraZeneca and Daiichi Sankyo, which put pressure on rival Gilead. And with CAR-T therapies now established, attention has shifted to other emerging approaches for training the immune system to attack tumors.

Read on for updates on Gilead, bispecific antibodies for blood cancer and gamma delta cell therapy.

ASCO is an important conference for any biotech developing a cancer drug. But this years meeting was particularly so for Gilead, which has spent a decade and billions of dollars trying to build its oncology business. Analysts and investors were eagerly awaiting the details of a key study of the breast cancer drug Trodelvy, for which it paid $21 billion to acquire last year. Updates were also expected for magrolimab, another cancer medicine Gilead recently bought in a large deal.

The drugs either underwhelmed or were upstaged by others, however. Trodelvy led to a 1.5-month improvement over chemotherapy on a measure of tumor progression in a late-stage study of patients with a common form of metastatic breast cancer. The result fell short of the 2-month target doctors surveyed by analyst firm RBC Capital Markets felt would warrant meaningful use, according to a research note.

Trodelvy was also overshadowed by AstraZeneca and Daiichi Sankyos rival breast cancer drug, Enhertu, whose data in so-called HER2 low tumors were so striking they received a standing ovation at the meeting.

All the enthusiasm for Trodelvy has evaporated after those results, wrote Baird analyst Brian Skorney in a note on Sunday, adding that Enhertus likely approval in HER2 low breast cancer could limit Trodelvys revenue potential.

Analysts were similarly unimpressed by the latest data for magrolimab, a blood cancer drug that was slowed by safety concerns this year. Initial data showed a response rate of 50% for a combination of magrolimab and the chemotherapy azacitidine in an early-stage trial in myelodysplastic syndrome. That rate has fallen to 33% with additional data, barely surpassing whats been observed in tests of chemotherapy alone, Skorney wrote.

Complete response rates slipped in a Phase 1 acute myeloid leukemia study as well. The updates show Gileads drug has sufficient activity, though its perhaps not the home run it was initially hoped to be, wrote RBC analyst Brian Abrahams in a note to clients.

Gilead will likely need to show more before investors view the cancer portfolio as a major growth driver, Abrahams added. Shares ticked down 2% in early Monday trading.

The biotech did get a reprieve on Friday, however, announcing that regulators had lifted their last remaining hold on studies of magrolimab in lymphoma and multiple myeloma.

Cell therapy has become a powerful new treatment option for blood cancers like lymphoma and multiple myeloma. Approved drugs from Gilead, Bristol Myers Squibb, Novartis and Johnson & Johnson use souped-up immune cells genetically modified and infused back into patients to attack cancers.

But the approach, while potent, involves a painstaking manufacturing process that requires physicians to carefully time treatment. In multiple myeloma, Bristol Myers and J&J have struggled to keep up with demand, Stat News has reported, further complicating cell therapy's use.

While drugmakers expect to overcome those hurdles with time, they are busy advancing other ways to redirect immune cells to target cancer. One alternative uses an antibody to latch onto protein flags found on the surface of immune cells and their cancerous targets, bringing them into tumor-killing contact.

These so-called bispecific antibodies have already shown promise in some of the same blood cancers addressed by CAR-T cell therapies. At ASCO, Roche and J&J revealed updated clinical trial data supporting their respective medicines for lymphoma and multiple myeloma. AbbVie and partner Genmab, meanwhile, will present data on their lymphoma bispecific antibody at the European Hematology Association's meeting next weekend.

Scott Gottlieb, formerly Food and Drug Administration commissioner and currently a member of Pfizers board, pointed to bispecific antibody data as some of the most exciting to come out of ASCO this year.

"That data looks very promising," he said on CNBCs Squawkbox program Monday, noting the therapies from Roche and partners AbbVie and Genmab specifically.

Specifically, Roche's data showed treatment led to responses in half of patients with relapsed or refractory diffuse large B-cell lymphoma who were treated in the study. Nearly 40% went into remission.

Notably, about a third of the 154 participants had previously received CAR-T therapies, which have recently been approved in the U.S. for earlier use in treating advanced lymphoma.

"We still need longer follow-up for the bispecific antibodies," said Kerry Savage, a medical oncologist at The University of British Columbia, who discussed Roche's abstract at ASCO on Friday. "We don't know the curative potential yet, but it's certainly encouraging so far."

AbbVie and Genmab's results, which will be presented on Saturday at EHA, showed a slightly higher overall response rate of 63% and a similar remission rate of 39% among adults with several variations of relapsed or refractory large B-cell lymphoma.

J&J, meanwhile, brought updated data to ASCO for its multiple myeloma bispecific teclistamab, which were also published in The New England Journal of Medicine. The data showed treatment could beat back cancer and, in about 40% of patients, lead to remission.

"The high rate of deep and durable responses in this population indicates the potential for teclistamab to provide substantial clinical benefit to a broader population of patients," researchers wrote in NEJM.

The search for more convenient alternatives to personalized cell therapies has led to other off-the-shelf strategies besides bispecific antibodies. One emerging approach involves gamma delta T cells, rare white blood cells that can recognize a range of targets.

Adicet Bio, In8Bio, Immatics, among others, are developing treatments and multiple large companies have shown interest in their work. Bristol Myers Squibb just last week expanded an existing deal with Immatics, while Takeda and Johnson & Johnson have recently made investments, too.

Adicets program, a potential treatment for non-Hodgkins lymphoma, is the most advanced of the group, making its trial results an important proof point for the field.

Prior to the meeting, Adicet said four of six treated patients with a low or medium dose went into remission, with two of the three patients treated still cancer free after three months. Importantly, there were no serious immune or neurological side effects reported.

At ASCO, Adicet disclosed results from two additional patients as well as longer follow-up from others. While early, the findings are in the range with CAR-T therapy. As of May 31, six of eight patients including two at the highest tested dose had responded to treatment. All six initially went into remission.

Notably, these were heavily pretreated patients, three of whom whose disease had progressed after CAR-T. Adicet hasnt reported any cases of severe cytokine release syndrome, a common side effect of CAR-T.

Yet the treatments durability remains in question. Though four of the complete responses are ongoing, only one has lasted longer than six months. One patient previously in remission died from COVID-19, while another relapsed.

Adicet plans to pick a dose to advance into further testing. The company amended its trial to include a higher dose as well as potentially evaluate a multiple-dose regimen, a strategy other off-the-shelf cell therapy developers are testing as well.

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ASCO 2022: Gilead's tough weekend, bispecific progress and 'gamma delta' cell therapy - BioPharma Dive

An acceptable safety profile and durable complete response (CR), partial response (PR) rates were observed with the chimeric antigen receptor (CAR) T-cell therapy CTX130 in the phase 1 COBALT-LYM study of patients with relapsed/refractory T-cell lymphomas, said Swaminathan P. Iyer, MD, professor of medicine in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center.

Iyer served as lead author of a study presented today at the 2022 European Hematology Association (EHA) Congress, titled, "The COBALT-LYM Study of CTX130: A Phase 1 Dose Escalation Study of CD70-Targeted Allogeneic CRISPR-Cas9Engineered CAR-T Cells in Patients with Relapsed/Refractory (R/R) T-cell Malignancies.

Transcript

What is the mechanism of action for CTX130 in T-cell lymphoma, and can you discuss how the COBALT-LYM study was conducted?

So, CTX130 is a first-in-class allogeneic CAR T-cell for T-cell lymphomas. And the study that put together this CAR T was called the COBALT-LYM study, and the target here is CD70, [which] is a protein that is expressed on the surface of cells. It's been found that 85% of T-cell lymphomas express them.

A lot of investigations of the past have been done on CD70 in terms of antibodies and antibody drug conjugates. What's different about this construct, it's an allogeneic CAR T, which means healthy donors are selected and the chimeric antigen receptor is created using CD70 as a construct, and using the other activation and costimulatory domains.

This is the product, CTX130, and this a phase 1 dose-finding study allowable in patients who express at least greater than 10% of CD70 in patients with PTCL [peripheral t-cell lymphoma] and patients with CTCL [transformed cutaneous t-cell lymphoma]. For PTCL, the prior criteria is one prior line of therapy, for CTCL its at least 2 systemic therapies.

The patients were enrolled, and you will see the presentation this afternoon, from the abstract, it's 18 patients data who participated in this study, and 70% overall response rate and 29% CR based on the abstract. So, this is the CTX130, and there's more data that will be presented this afternoon.

Can you discuss efficacy and safety findings reported at EHA2022 of the COBALT-LYM study?

So, the first thing is safety. Since it's a dose-finding study, phase 1, the main goal of part A, which is the dose escalation, is safety. Since it's a CAR T construct, it has certain potential side effects that are very different from other drugs, if you will.

So, the things that you would expect in CAR Ts are cytokine release syndrome [CRS], the neurological toxicity called ICANS [immune effector cell-associated neurotoxicity syndrome], and since its an allogeneic CAR T, GVHD [graft versus host disease], and since it's an effective therapy, tumor lysis syndrome (TLS), and then everything else that other drugs might cause.

So, in this particular study, the safety was acceptable across all those levels4 of those levels tested, 1, 2, 3, and 4, going from 30 to 900 million cells, and the safety was acceptable. The CRS was mostly grade 1 and 2, the neurological toxicity was grade 1 and 2, all of which resolved. There was no TLS, no GVHD.

There were some infections seen. One out of the 4 infections of the grade 3 or higher were attributable to the CAR T, but otherwise, there are other treatment-emergent SAEs [serious adverse events], such as syncope, presyncope, tumor hemorrhagethey were all not deemed related to CTX130. So, safety wise, very acceptable.

Efficacy, I just mentioned 70% overall response rate with 29% CRs. And some of these CRs were durable CRs. You will see that many of them could be bridged to the more longer-term consolidation therapy. But for the first time you're seeing responses in T-cell lymphomas, patients who did not achieve prior responses like a CR, and now we're getting to the point where you have PRs and CRs that are lasting.

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Dr Swaminathan P. Iyer on Efficacy, Safety of CD70-Targeted CAR T-Cell Therapy in R/R T-Cell Lymphoma - AJMC.com Managed Markets Network

DUBLIN--(BUSINESS WIRE)--The "Single Cell Sequencing Market Research Report by Product (Consumables and Instruments), Application, End-User, Region (Americas, Asia-Pacific, and Europe, Middle East & Africa) - Global Forecast to 2027 - Cumulative Impact of COVID-19" report has been added to ResearchAndMarkets.com's offering.

The Global Single Cell Sequencing Market size was estimated at USD 2,301.59 million in 2021, USD 2,407.37 million in 2022, and is projected to grow at a Compound Annual Growth Rate (CAGR) of 4.77% to reach USD 3,044.54 million by 2027.

Competitive Strategic Window:

The Competitive Strategic Window analyses the competitive landscape in terms of markets, applications, and geographies to help the vendor define an alignment or fit between their capabilities and opportunities for future growth prospects. It describes the optimal or favorable fit for the vendors to adopt successive merger and acquisition strategies, geography expansion, research & development, and new product introduction strategies to execute further business expansion and growth during a forecast period.

FPNV Positioning Matrix:

The FPNV Positioning Matrix evaluates and categorizes the vendors in the Single Cell Sequencing Market based on Business Strategy (Business Growth, Industry Coverage, Financial Viability, and Channel Support) and Product Satisfaction (Value for Money, Ease of Use, Product Features, and Customer Support) that aids businesses in better decision making and understanding the competitive landscape.

Market Share Analysis:

The Market Share Analysis offers the analysis of vendors considering their contribution to the overall market. It provides the idea of its revenue generation into the overall market compared to other vendors in the space. It provides insights into how vendors are performing in terms of revenue generation and customer base compared to others. Knowing market share offers an idea of the size and competitiveness of the vendors for the base year. It reveals the market characteristics in terms of accumulation, fragmentation, dominance, and amalgamation traits.

The report provides insights on the following pointers:

1. Market Penetration: Provides comprehensive information on the market offered by the key players

2. Market Development: Provides in-depth information about lucrative emerging markets and analyze penetration across mature segments of the markets

3. Market Diversification: Provides detailed information about new product launches, untapped geographies, recent developments, and investments

4. Competitive Assessment & Intelligence: Provides an exhaustive assessment of market shares, strategies, products, certification, regulatory approvals, patent landscape, and manufacturing capabilities of the leading players

5. Product Development & Innovation: Provides intelligent insights on future technologies, R&D activities, and breakthrough product developments

The report answers questions such as:

1. What is the market size and forecast of the Global Single Cell Sequencing Market?

2. What are the inhibiting factors and impact of COVID-19 shaping the Global Single Cell Sequencing Market during the forecast period?

3. Which are the products/segments/applications/areas to invest in over the forecast period in the Global Single Cell Sequencing Market?

4. What is the competitive strategic window for opportunities in the Global Single Cell Sequencing Market?

5. What are the technology trends and regulatory frameworks in the Global Single Cell Sequencing Market?

6. What is the market share of the leading vendors in the Global Single Cell Sequencing Market?

7. What modes and strategic moves are considered suitable for entering the Global Single Cell Sequencing Market?

Market Dynamics

Drivers

Restraints

Opportunities

Challenges

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/nel4wa

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Insights on the Single Cell Sequencing Global Market to 2027 - Ongoing Demand for Personalized or Customized Medicine Presents Opportunities -...

BOSTON--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that five scientific abstracts on the companys portfolio of cystic fibrosis (CF) medicines will be presented at the European Cystic Fibrosis Society's (ECFS) 45th European Cystic Fibrosis Conference held June 8-11, 2022, in Rotterdam, the Netherlands.

Vertex will present the first analysis of data collected in the U.S. CF Foundation Patient Registry (CFFPR) of over 16,000 people with CF treated with TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for an average of nine months. This first interim analysis of an ongoing five-year post-authorization study (abstract WS22.05) showed that real-world treatment with TRIKAFTA was associated with improved lung function and a 77% reduced risk of pulmonary exacerbations compared to pre-TRIKAFTA baseline, as well as an 87% lower risk of lung transplant and a 74% lower risk of death, compared to the historical 2019 U.S. CFFPR population. No new safety concerns were identified.

Vertex will also present data comparing the annual rate of lung function change in people with CF ages 12 years and older with two F508del mutations (F/F) or one F508del mutation and one minimal function mutation (F/MF) treated with TRIKAFTA in pivotal studies and an open-label extension study compared to propensity-score matched historical CFTR-modulator-untreated controls from the U.S. CFFPR (abstract WS22.04). Results show that TRIKAFTA demonstrated on average no decrease in ppFEV1 over a two-year period in this population, in contrast to declines seen in the matched controls. The analysis indicates that treatment with TRIKAFTA has a significant impact on the trajectory of CF lung disease.

Additionally, Vertex will present data from a long-term real-world study demonstrating that initiating KALYDECO (ivacaftor) early in life (ages 6-10 years) preserves lung function to a greater extent than if KALYDECO is initiated at an older age (abstract WS17.03). These results show the importance of early initiation of KALYDECO for eligible patients.

These long-term and real-world studies show the potentially transformative benefits of treatment with CFTR modulators and add to the substantial body of evidence supporting treatment as early in life as possible, said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. We continue to make rapid progress in developing medicines that treat the underlying cause of CF, and today, we are closer to our goal of developing highly effective therapies for all patients with CF than ever before.

Additional Presentations

In addition to the studies noted above, other Vertex presentations at the conference this year support the long-term and early use of CFTR modulators:

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing the CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the early 30s.

About TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor)

In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface by binding to different sites on the CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of elexacaftor, tezacaftor and ivacaftor help hydrate and clear mucus from the airways.

TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one copy of the F508del mutation, or another mutation responsive to TRIKAFTA, in the CFTR gene. Patients should talk to their doctor to learn if they have an indicated CF gene mutation. It is not known if TRIKAFTA is safe and effective in children under 6 years of age.

Please see Important Safety Information below and [click here] for full U.S. Prescribing Information.

About KALYDECO (ivacaftor)

In people with certain types of mutations in the CFTR gene, the CFTR protein at the cell surface does not function properly. Known as a CFTR potentiator, ivacaftor is an oral medicine designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. KALYDECO (ivacaftor) was the first medicine to treat the underlying cause of cystic fibrosis (CF) in people with specific mutations in the CFTR gene.

KALYDECO is a prescription medicine used for the treatment of CF in patients aged 4 months and older who have at least one mutation in their CF gene that is responsive to KALYDECO. Patients should talk to their doctor to learn if they have an indicated CF gene mutation. It is not known if KALYDECO is safe and effective in children under 4 months of age.

Please see Important Safety Information below and [click here] for full U.S. Prescribing Information.

About ORKAMBI (lumacaftor/ivacaftor)

In people with two copies of the F508del mutation, the CFTR protein is not processed and trafficked normally within the cell, resulting in little to no CFTR protein at the cell surface.

ORKAMBI (lumacaftor/ivacaftor) is an oral medicine that is a combination of lumacaftor and ivacaftor. Lumacaftor is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del-CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of lumacaftor and ivacaftor help hydrate and clear mucus from the airways.

ORKAMBI is a prescription medicine used for the treatment of CF in patients age 2 years and older who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene. ORKAMBI should only be used in these patients. It is not known if ORKAMBI is safe and effective in patients under 2 years of age.

Please see Important Safety Information below and [click here] for full U.S. Prescribing Information.

IMPORTANT SAFETY INFORMATION for TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor), KALYDECO (ivacaftor), and ORKAMBI (lumacaftor/ivacaftor)

Patients should not take KALYDECO or TRIKAFTA if they take certain medicines or herbal supplements, such as: the antibiotics rifampin or rifabutin; seizure medicines such as phenobarbital, carbamazepine, or phenytoin; or St. Johns wort.

Patients should not take ORKAMBI if they take certain medicines or herbal supplements, such as: the antibiotics rifampin or rifabutin; the seizure medicines phenobarbital, carbamazepine, or phenytoin; the sedatives and anti-anxiety medicines triazolam or midazolam; the immunosuppressant medicines cyclosporine, everolimus, sirolimus, or tacrolimus; or St. Johns wort.

Before taking KALYDECO, ORKAMBI, or TRIKAFTA patients should tell their doctor about all of their medical conditions, including if they: have or have had liver problems; have kidney problems; are pregnant or plan to become pregnant because it is not known if KALYDECO, ORKAMBI, or TRIKAFTA, will harm an unborn baby; or are breastfeeding or planning to breastfeed because it is not known if KALYDECO, ORKAMBI, or TRIKAFTA passes into breast milk. Before taking ORKAMBI, patients should tell their doctor if they have had an organ transplant, or if they are using a hormonal contraceptive including oral, injectable, transdermal, or implantable form as this should not be used as a method of birth control when taking ORKAMBI.

KALYDECO, ORKAMBI, or TRIKAFTA may affect the way other medicines work, and other medicines may affect how KALYDECO, ORKAMBI, or TRIKAFTA work. Therefore, the dose of KALYDECO, ORKAMBI, or TRIKAFTA may need to be adjusted when taken with certain medications. Patients should especially tell their doctor if they take antifungal medications such as ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole; or antibiotics such as telithromycin, clarithromycin, or erythromycin.

KALYDECO or TRIKAFTA can cause dizziness in some people who take it. Patients should not drive a car, use machinery, or do anything that needs them to be alert until they know how KALYDECO or TRIKAFTA affects them.

When taking ORKAMBI, patients should tell their doctor if they stop taking ORKAMBI for more than 1 week as their doctor may need to change the dose of ORKAMBI or other medicines the patient is taking.

Patients should avoid food or drink containing grapefruit while taking KALYDECO or TRIKAFTA.

KALYDECO, ORKAMBI, and TRIKAFTA can cause serious side effects, such as:

Liver damage and worsening of liver function in people taking TRIKAFTA with severe liver disease that can be serious and may require transplantation. Liver damage has also happened in people without liver disease.

High liver enzymes in the blood have been reported in patients receiving KALYDECO, ORKAMBI, or TRIKAFTA. The patient's doctor will do blood tests to check their liver before starting treatment with KALYDECO, ORKAMBI, or TRIKAFTA; every 3 months during the first year of treatment; and every year while on treatment. For patients who have had high liver enzymes in the past, the doctor may do blood tests to check the liver more often. Patients should call their doctor right away if they have any of the following symptoms of liver problems: pain or discomfort in the upper right stomach (abdominal) area; yellowing of their skin or the white part of their eyes; loss of appetite; nausea or vomiting; or dark, amber colored urine.

Worsening of liver function in people with severe liver disease taking ORKAMBI. The worsening of liver function can be serious or cause death. Talk to your doctor if you have been told you have liver disease as your doctor may need to adjust the dose of ORKAMBI.

Breathing problems such as shortness of breath or chest tightness in patients when starting ORKAMBI, especially in patients who have poor lung function. If a patient has poor lung function, their doctor may monitor them more closely when starting ORKAMBI.

An increase in blood pressure in some people receiving ORKAMBI. The patients doctor should monitor their blood pressure during treatment with ORKAMBI.

Abnormality of the eye lens (cataract) in some children and adolescents treated with KALYDECO, ORKAMBI, or TRIKAFTA. If the patient is a child or adolescent, their doctor should perform eye examinations before and during treatment with KALYDECO, ORKAMBI, or TRIKAFTA to look for cataracts.

The most common side effects of KALYDECO include headache; upper respiratory tract infection (common cold), which includes sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness.

The most common side effects of ORKAMBI include breathing problems, such as shortness of breath and chest tightness; nausea; diarrhea; fatigue; increase in a certain blood enzyme called creatinine phosphokinase; rash; gas; common cold, including sore throat, stuffy or runny nose; flu or flu-like symptoms; and irregular, missed, or abnormal periods (menses) and increase in the amount of menstrual bleeding. Additional side effects seen in children include cough with sputum, stuffy nose, headache, stomach pain, and increase in sputum.

The most common side effects of TRIKAFTA include headache; diarrhea; upper respiratory tract infection (common cold), including stuffy and runny nose; stomach (abdominal) pain; inflamed sinuses; increase in liver enzymes; increase in a certain blood enzyme called creatine phosphokinase; rash; flu (influenza); and increase in blood bilirubin.

These are not all the possible side effects of KALYDECO, ORKAMBI, or TRIKAFTA. Please click product link to see the full U.S. Prescribing Information for KALYDECO, ORKAMBI, or TRIKAFTA.

About Vertex

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

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 12 consecutive years on Science magazine's Top Employers list and one of the 2021 Seramount (formerly Working Mother Media) 100 Best Companies. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements made by Dr. Bozic in this press release, statements regarding the potential benefits, safety and efficacy of our products, and our plans to present data about our portfolio of CF products at the ECFS European Cystic Fibrosis Conference, including an analysis of data from the ongoing five-year post-authorization safety study for TRIKAFTA, data comparing the annual rate of lung function change in certain individuals with CF and our assessment of the impact of such data, data regarding the early initiation of KALYDECO and our assessment of the impact of such data, and additional scientific presentations regarding our marketed CF products, including expectations regarding the abstracts that will be made available at the ECFS European Cystic Fibrosis Conference. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration, approval or further development of its compounds due to safety, efficacy or other reasons, risks related to approval and commercialization of our medicines, and other risks listed under the heading Risk Factors in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission (SEC) and available through the company's website at http://www.vrtx.com and on the SECs website at http://www.sec.gov. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

Read more:
Vertex to Present Data Demonstrating Significant Benefits of Long-Term and Early Treatment With CFTR Modulators at the European Cystic Fibrosis...

The longest duration of reduction in red blood cell transfusion dependence was reported among patients with -thalassemia who received continued treatment with luspatercept-aamt in the updated data from the phase 3 BELIEVE trial.

The longest duration of reduction in red blood cell (RBC) transfusion dependence was reported among patients with -thalassemia who received continued treatment with luspatercept-aamt (Reblozyl) in the updated data from the phase 3 BELIEVE trial (NCT02604433), presented at the 2022 EHA Congress.1

Response was assessed as reduction of RBC transfusion burden by at least 33% from baseline and by at least 50% from baseline among patients who received luspatercept vs placebo during any rolling 12- or 24-week interval. With a long-term data cutoff of January 5, 2021, among the 224 patients in the luspatercept arm, 173 patients (77.2%) had at least 33% response during any 12-week interval and 116 (51.8%) had a response during any 24-week interval. A transfusion burden reduction of at least 50% was reported among 112 patients (50%) and 53 patients (23.7%) during any 12- and 24-week interval, respectively.1

These outcomes were compared with prior data cutoff landmarks: May 11, 2018 (primary data cutoff) and January 7, 2019 (intermediate data cutoff). In the primary analysis, 70.5% and 41.1% of patients had at least a 33% reduction in transfusion burden at the 12- and 24-week intervals. These rates were 76.3% and 45.1% in the intermediate analysis, respectively. Reduction of at least 50% were reported at any 12- and 24-week intervals among 40.2% and 16.5% of patients, respectively, in the primary analysis and 44.6% and 20.5% in the intermediate analysis.1

In terms of transfusion independence, at the cutoff of 3 years 12% of patients [who received] luspatercept, achieved transfusion independence, equal to or more than [8] weeks. And that, of course, implies the longest interval of this condition of transfusion in dependence, said Maria Domenica Cappellini, MD, FRCP, FACP, professor of internal medicine at the University of Milan and chief of the Rare Diseases Centre at the Fondazione IRCCS Policlinico Hospital in Italy, during a presentation of the data.

The median longest duration of RBC transfusion independence was 72 days (95% CI, 62-103) with longer-term luspatercept treatment. At the primary and intermediate analysis cutoffs, the rates of RBC transfusion independence lasting at least 8 weeks were 10.7% and 11.2%, respectively, compared with 12.1% in the longer-term analysis.

Continuous treatment with the luspatercept allowed for more patients to experience a reduction in RBC transfusion burden, with longer durations of responses compared [with] the previous cutoff, Cappellini said. We are confident that these [benefits] will be even more clear with longer follow-up and patients with transfusion dependent -thalassemia treated in the BELIEVE study will continue to benefit from luspatercept with over 3 years of treatment.

Additional data showed that the median duration of RBC transfusion burden reduction was 114 days (95% CI, 107-137) and 99 days (95% CI, 95-104) for those with 33% reduction and 50% reduction, respectively, at the long-term analysis cutoff. In the primary data cutoff analysis, the median duration of RBC transfusion burden reduction was 104 days (95% CI, 84-588) for those with at least 33% reduction and 97.5 days (95% CI, 84-588) for those with at least 50% reduction. In the intermediate analysis the median duration was 105 days (95% CI, 84-825) and 99 days (95% CI, 84-825), respectively.

The median treatment duration during the primary, intermediate, and long-term landmark analyses were 64.1 days (95% CI, 3-97), 95.7 days (95% CI, 1.7-128.1), and 153.6 days (95% CI, 1.7-215).

Further, the mean cumulative duration of RBC transfusion burden reduction during any rolling 12-week interval was 627.3 (standard deviation, 390.5) for patients who received luspatercept.1

In terms of RBC transfusion burden change from baseline, Cappellini noted that patients receiving luspatercept required fewer units of blood over time. The mean change in RBC units every 48 weeks from baseline was 4.8 (weeks 1-48), 5.6 (weeks 49-96), 6.2 (weeks 97-144), and 6.4 (weeks 145-192) compared with a 1.1 unit increase reported in weeks 1-48 with placebo.

Cappellini also highlighted that patients achieving an RBC transfusion burden reduction of 50% or higher experienced a greater interval between the transfusions compared with the baseline over time at a mean of +9.9 days (standard deviation, 22.0).1

Luspatercept, an erthyroid maturation agent, is approved for the treatment of anemia in patients with -thalassemia who require regular red blood cell (RBC) transfusions. Additionally, it received an indication for patients who require 2 or more RBC units over 8 weeks for patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts or with MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.2

BELIEVE was a randomized, double-blind, study comparing luspatercept with placebo.1,3 Investigators enrolled adults with -thalassemia who required regular transfusions of 6 to 20 RBC units in the 24 weeks prior to random assignment, with no transfusion-free period (35 days). Patients were randomly assigned 2:1 to luspatercept (n = 224) plus best supportive care or placebo plus best supportive care (n = 112). Luspatercept was administered subcutaneously 1.0 mg/kg (up to a maximum dose of 1.25 mg/kg) every 3 weeks. Best supportive care included RBC transfusions to maintain baseline hemoglobin levels and iron chelation therapy.1,3

The primary end point was reduction of RBC transfusion burden by at least 33% from baseline with a reduction of at least 2 units in weeks 13 to 24 compared with the 12 weeks prior to randomization.3

Baseline characteristics between the experimental and control arm were well balanced. The median age was 30 years (range, 18-66). Median hemoglobin levels at 24 weeks were 9.31 g/dL (range, 4.5-11.4) and 9.15 g/dL (range, 5.8-11.7) in the luspatercept arm and placebo arm, respectively. The median RBC transfusion burden was 6.12 units (range, 3-14) every 12 weeks in the luspatercept arm and 6.27 (range, 3-12) in the placebo arm. The median burden every 24 weeks was 14 units (range, 6-24) and 15 (range, 6-26), respectively. Further, over half of patients (57.6% and 58.0%, respectively) had a splenectomy.

In terms of liver iron concentration (LIC), at baseline the median LIC in the luspatercept arm was 6.4 mg/g dry weight (range, 0.8-125.0) and 5.05 mg/g dry weight (range, 0.2-53.2) in the placebo arm. An analysis of LIC is ongoing, according to Cappellini.

At data cutoff 127 patients (56.7%) remained on study treatment and 2.7% (n = 6) have completed 192 weeks of treatment. Of the 224 patients in the luspatercept arm, 96 (42.9%) discontinued treatment. The most common reasons for discontinuation were physician decision (23.7%), adverse event (10.3%), or other (5.4%).

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Long-term Treatment With Luspatercept Reduces Transfusion Dependence Associated With -Thalassemia - OncLive

More than a dozen rectal cancer patients in the United States have seen their cancer disappear after undergoing experimental immunotherapy, in what doctors are calling an astonishing result.

The patients, who were part of a small clinical trial led by researchers from New Yorks Memorial Sloan Kettering (MSK) Cancer Center, saw their tumours vanish after being treated with an experimental drug called dostarlimab.

Details of the trial were published on Sunday in the New England Journal of Medicine.

The paper described the results of 12 patients with rectal cancer, all of whom saw their cancer vanish after treatment with dostarlimab.

Participants received a dose of dostarlimab every three weeks for six months, with the idea being that they would need to undergo standard treatments of chemotherapy, radiation therapy and surgery following treatment.

However, researchers found that in every case, the cancer was cleared through the experimental treatment alone.

The trial has been hailed as a first in cancer treatment, with one of the papers authors, Dr Luis Diaz Jr of Memorial Sloan Kettering, telling the New York Times that he knew of no other study in which a treatment completely obliterated a cancer in every patient.

I believe this is the first time this has happened in the history of cancer, he said.

Immunotherapy harnesses the bodys own immune system to identify and destroy cancer cells.

The trial focussed on a subset of rectal cancer patients whose cancer had a specific mutation, MSK said in a statement.

This sort of rectal cancer, known as "mismatch repair-deficient" (MMRd) rectal cancer, tends to respond poorly to standard chemotherapy regimens. In the trial, researchers wanted to investigate if immunotherapy alone could beat rectal cancer that had not spread to other tissues, the organisation said.

The research, which is ongoing, has seen at least 14 patients and counting have their tumours disappear, with none of them experiencing significant side effects, it added.

There was no need for standard treatments of radiation, surgery, or chemotherapy, and the cancer has not returned in any of the patients, who have been cancer-free for up to two years, it said.

Its incredibly rewarding to get these happy tears and happy emails from the patients in this study who finish treatment and realise, Oh my God, I get to keep all my normal body functions that I feared I might lose to radiation or surgery, said Dr Andrea Cercek of Memorial Sloan Kettering, who co-led the trial.

Inspiration for the study came from a previous trial led by Dr Diaz, which saw patients taking a drug called pembrolizumab, the New York Times reported. That trial, which involved patients with advanced cancer that resisted standard treatment, saw participants tumours stabilise, shrink and even vanish.

In the current trial, researchers wanted to see what a similar drug, dostarlimab, would do if used before the cancer cells had a chance to spread.

This sort of treatment focuses on particular proteins called checkpoints, which are made by some types of immune system cells as well as some cancer cells, according to the USNational Cancer Institute. The checkpoints, which keep immune responses from being too strong, can sometimes prevent immune cells from effectively killing cancer cells.

Like pembrolizumab, dostarlimab is a checkpoint inhibitor: It essentially releases the brakes on an immune cell, freeing it to recognise and attack cancer cells, according to MSK.

When the brakes are taken off the immune cells, MMRd cells look especially strange because they have so many mutations. So the immune cells attack with much more force, Dr Cercek said.

The results have provided what may be an early glimpse of a revolutionary treatment shift, Dr Hanna Sanoff, an oncologist at the Lineberger Comprehensive Cancer Center at the University of North Carolina, who was not involved in the trial, wrote in an editorial accompanying the paper.

However, she added that although the results are cause for great optimism, such an approach cannot yet supplant our current curative treatment approach.

Whether the results of this small study conducted at Memorial Sloan Kettering Cancer Center will be generalisable to a broader population of patients with rectal cancer is also not known, she said.

In order to provide more information regarding which patients might benefit from immunotherapy, subsequent trials should aim for heterogeneity in age, coexisting conditions, and tumour bulk.

The clinical trial is continuing to enrol patients and is growing, the MSK researchers said. They are also investigating to see if the same method can beat other cancers, and are looking at patients with gastric (stomach), prostate, and pancreatic cancers.

Excerpt from:
This breakthrough drug trial saw cancer vanish in every patient - Euronews

Karen L. Reckamp, MD, explains the need for more treatment options for patients with nonsmall cell lung cancer who have been previously treated with immune checkpoint inhibitors and develop resistance.

Karen L. Reckamp, MD, a professor in Medicine, and director of the Division of Medical Oncology at Cedars-Sinai Medical Center, as well as a medical oncologist at the Samuel Oschin Cancer Center, explains the need for more treatment options for patients with nonsmall cell lung cancer (NSCLC) who have been previously treated with immune checkpoint inhibitors (ICIs) and develop resistance.

As upfront treatment for NSCLC, the majority of patients are administered immunotherapy with chemotherapy or immunotherapy alone. Although these strategies are very beneficial to patients, disease progression is inevitable, and some patients become resistant to their frontline regimen.

Once a tumor grows too large or patients are ICI refractory, no effective therapies are available. The Lung-MAP nonmatched substudy S1800A was designed to address the need for treatment option after frontline ICI therapy in patients with NSCLC. The phase 2 clinical trial (NCT03971474) investigates the combination of ramucirumab (Cyramza) and pembrolizumab (Keytruda) vs standard of care.

0:08 | All patients now receive either a combination of immunotherapy and chemotherapy or immunotherapy alone as part of their frontline treatment for advanced nonsmall cell lung cancer. We're also starting to use immunotherapy in the treatment of earlier stage nonsmall cell lung cancer. So, most patients do get exposed to immune checkpoint inhibitors at some point during their therapy. And we know though there are great benefits that patients experience most will have tumor progression and develop some tumor resistance to immune checkpoint inhibitors.

0:47 | At this moment in time, we don't have the best therapies. We don't know the best therapies to provide patients once a tumor has grown on immune checkpoint inhibition and chemotherapy. So, this study is to evaluate what might be better therapies than our standard of care which generally include

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Challenging the Standards of Care for ICI-Pretreated Patients With NSCLC - Targeted Oncology

Usually contained in the human physique, T cells are assigned the obligation to detect and battle threatening micro organism or viruses. T cells guard and defend our immune system. Most cancers cells are a definite story. Most cancers cells are sneaky. They duplicate and switch throughout the physique in a stealthy technique inflicting points and havoc. Sadly for the immune system, T cells are normally not always able to detect most cancers cells.

Within the earlier, there have been many challenges treating positive types of blood and bone marrow cancers along with leukemia, lymphoma, and quite a few myeloma.

That is the place CAR T-cell treatment can step in and alter the immune system paradigm.

Here is the best way it really works. Step one is to retrieve frequent T cells from the affected individual or a specific donor. The affected individual or donors blood sample goes to a lab. The T cells are then separated from the blood. A singular receptor that binds to positive proteins on most cancers cell surfaces is added to the T cells. This imported receptor is named the chimeric antigen receptor or CAR. These new and improved T cells are administered once more into the physique like a blood transfusion.

As soon as the CAR T cells enter the physique, theyll destroy cancerous cells along with tumors. The excellent news is that these modified CAR T cells will not impact healthful cells. It is a win-win situation.

In 2017, the Moffitt Malignant Hematology & Mobile Remedy program was established in partnership with Memorial Healthcare System. Oncologists now have additional decisions to take care of blood and bone marrow most cancers victims. Medical professionals can also conduct evaluation that will revenue every newly recognized and relapsed blood most cancers victims.

Malignant Hematology & Mobile Remedy at Memorial Healthcare System, located on the campus of Memorial Hospital West, is the one facility in Broward and Palm Seaside counties to provide this array of distinctive corporations and most cancers treatments.

Were at all times trying to present our group probably the most progressive and highest high quality healthcare obtainable anyplace, says Memorial Hospital West CEO Vedner Guerrier, and this development with our companions at Moffitt does that for most cancers sufferers.

CAR T-cell treatment must be considered for a number of kinds of most cancers:

Diffuse large B-cell lymphoma

Mantle cell lymphoma

Acute lymphoblastic leukemia

A number of myeloma

Follicular lymphoma

Remodeled follicular lymphoma

Major mediastinal B cell lymphoma

We see 70-80 new a number of myeloma instances every year and greater than 300 with relapse illness so, whereas not each affected person can be a CAR T candidate, were hoping many extra can be as progress continues, acknowledged Dr. Claudia Paba Prada, an assistant member of Moffitt Malignant Hematology and Mobile Remedy at Memorial Healthcare System. Were utilizing medicine underneath analysis that are not obtainable anyplace else in Florida.

Immunotherapy may be used to supply stem-cell transplants or preserve a higher top quality of life for victims who arent transplant candidates. CAR T-cell treatment can substitute or be used as a complement for chemotherapy. This implies the prospect for a lot much less toxins inside the physique all through most cancers remedy. In the long run new kinds of immunotherapies will help victims win the battle in the direction of most cancers.

For additional data, go to https://www.mhs.web/companies/most cancers/sorts/leukemia-lymphoma.

Content material provided by Memorial Healthcare System

Link:
CAR T-Cell Therapy: The New Way To Fight Cancer - Black Chronicle

video:The video shows the water build-up in the cathode channels during the first 600 s of the fuel cell start-up. The water starts to nucleate on the channel edges and corners. view more

Credit: HZB

"In a fuel cell, hydrogen and oxygen are combined to form water. This produces electrical energy," explains Ralf Ziesche from the imaging group at HZB. "Probably the most important component inside the fuel cell is the membrane." It is only about 20 micrometres thick (half as wide as a human hair) and connected with various functional layers to form a separation area about 600 micrometres wide inside the fuel cell.

"The membrane composite snatches the electrons from the hydrogen atoms. Only the hydrogen nuclei - the protons - can pass through the membrane." The electrons, on the other hand, flow off via an electrical connection and are used as an electric current. Air is let in on the other side of the separating wall. The oxygen it contains reacts with the protons that come through the membrane and the electrons that flow back from the other side of the electric circuit. Pure water is produced.

"Some of the water is discharged. Another part must remain in the fuel cell, because the membrane must not dry out," Ralf Ziesche explains. "But if there is too much water in it, the protons can no longer penetrate the membrane. Dead areas develop at these points, and the reaction can no longer take place there. The efficiency of the entire fuel cell drops." To allow hydrogen, air and water to flow in and out, tiny channels are milled into metal plates on both sides of the membrane. These channels can be used to optimise fuel cells and increase efficiency. Hereby, the channel design is the key for a balanced cell wetting and optimal efficiency.

To do this, it is advantageous to have as accurate a picture as possible of the water distribution within the channels. This was the goal of a collaboration between the research group from the Electrochemical Innovation Lab (EIL) at University College London (UCL) and HZB. "In principle, we subjected the fuel cell to computed tomography, as it is used in medicine," explains Nikolay Kardjilov from the imaging group at HZB. But while X-rays are used for medical analyses, Nikolay Kardjilov and his team preferred to use neutron radiation. "Because X-rays provide far too low an image contrast between hydrogen and water on one side and the metal structure on the other. Neutrons, on the other hand, are ideal here."

This was quite tricky. Because in order to get a three-dimensional image, the radiation source has to go around the object to be imaged. In medicine, this is quite easy to solve. There, the radiation source and scanner rotate around the patient, who is resting on a table. "But our radiation source was the Berlin Experimental Reactor BER II, where we had set up our imaging station CONRAD. And we can't simply rotate it around our fuel cell sample," says Nikolay Kardjilov. But with an engineering trick, his team managed to move the fuel cell, including the supply lines for hydrogen and air, the discharge line for water and the electric cables, into the neutron beam. "Until now, neutron imaging has only been able to produce two-dimensional images from inside the fuel cell. Now, for the very first time, we have also made the water distribution visible in three dimensions and in real time," the physicist is pleased to report. The BER II is shut down since the end of 2019. But the work will be continued as part of the joint research group "NI-Matters" between HZB, the Institut Laue-Langevin (ILL, France) and the University of Grenoble (France).

Kai Drfeld

Nature Communications

Experimental study

Not applicable

High-speed 4D neutron computed tomography for quantifying water dynamics in polymer electrolyte fuel cells

25-Mar-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Water distribution in the fuel cell made visible in 4D - EurekAlert

Scientists at the University of Toronto and Sinai Health say they have identified a new way to control the fate of neural stem cells, bringing researchers one step closer to unlocking the mystery of how to repair the brain after injury or stroke.

The findings, published recently in the journalNature Communications, outline a small set of molecules able to keep two major classes of neural stem cells from losing their ability to differentiate into critical components of a mammals cortex, a part of the brain that controls language and information processing.

This discovery is an exciting extension of platform technologies developed by our lab in recent years, which make cell therapy safe and universal with off-the-shelf products to treat degenerative diseases, saidAndras Nagy, who is principal investigator on the study,a professor ofobstetrics and gynaecologyU of Ts Temerty Faculty of Medicine,and a senior investigator at theLunenfeld-Tanenbaum Research Instituteat Sinai Health.

GABAergic and glutamatergic neurons are two major neuronal subtypes in the mammalian forebrain, or cerebral cortex. Both classes develop from cells known as neuroepithelial progenitors and play an early and important role in brain development, but then quickly lose their ability to form other cortical cell types.

To overcome this limitation, scientists in the Nagy lab identified a set of small molecules capable of keeping the progenitor cells growing without losing their developmental potential.

Furthermore, when researchers withdrew that cocktail of molecules from the stem cells, the cells continued to differentiate into cells of the human forebrainin large numbers.

The ability to obtain an unlimited number of forebrain-forming neural epithelium from stem cells is essential for disease modelling and toxicity testing needed in the development of new drugs, said Nagy, who is also affiliated with U of T'sInstitute of Medical Scienceand holds the Canada Research Chair in Stem Cells and Regeneration. These cells could be used in cell therapies, with the potential to treat strokes and other neurological diseases.

Balazs Varga, first author on the paper who developed cell-based therapeutic approaches over the span of a decade for the project, said that understanding the forces orchestrating brain development will help identify underlying causes of diseases, leading to new treatments.

"Our work identified one way we can control the fate of neural stem cells, said Varga, formerly a post-doctoral researcher in the Nagy lab who is now a research associate at Wellcome Trust Medical Research Council Cambridge Stem Cell Institute. Better understanding the behaviour of the neuroepithelial cells will provide us with ideas about how we could control progenitor cell function and brain regeneration.

The research was supported by the Canadian Institutes of Health Research.

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Researchers look to unleash the power of stem cells to repair brain injuries - University of Toronto