Category Archives: Stem Cell Medical Center

Quizartinib Added to Chemotherapy Demonstrates Superior Overall Survival Compared to Chemotherapy Alone in Adult Patients with Newly Diagnosed…

TOKYO & MUNICH & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced positive topline results from the global pivotal QuANTUM-First phase 3 trial evaluating quizartinib, a highly potent and selective FLT3 inhibitor, in patients with newly diagnosed FLT3-ITD positive acute myeloid leukemia (AML).1

QuANTUM-First met its primary endpoint, demonstrating that patients who received quizartinib in combination with standard induction and consolidation chemotherapy and then continued with single agent quizartinib had a statistically significant and clinically meaningful improvement in overall survival (OS) compared to those who received standard treatment alone. The safety of quizartinib was shown to be manageable and consistent with the known safety profile.

AML is one of the most common forms of leukemia in adults, representing about one-third of all cases.2 The five-year survival rate of AML is about 29%, and patients with FLT3-ITD positive AML have a particularly unfavorable prognosis, including an increased risk of relapse and shorter overall survival.1,3 There remains a high unmet need to improve survival for the majority of patients with AML.4

The results of the phase 3 QuANTUM-First trial showed that adding quizartinib, a potent and selective FLT3 inhibitor, to chemotherapy significantly prolonged overall survival in patients with newly diagnosed FLT3-ITD positive AML, said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. We look forward to sharing the QuANTUM-First data with the hematology community and will initiate discussions with global regulatory authorities.

Data from QuANTUM-First will be presented at an upcoming medical meeting and shared with regulatory authorities globally.

About QuANTUM-First

QuANTUM-First is a randomized, double-blind, placebo-controlled, multi-center global phase 3 study evaluating quizartinib in combination with standard induction and consolidation chemotherapy and then as continued single agent therapy in adult patients (age 18 75) with newly diagnosed FLT3-ITD positive AML.

Patients were randomized 1:1 into two treatment groups to receive quizartinib or placebo in combination with standard anthracycline and cytarabine-based induction and consolidation regimens. Eligible patients, including those who underwent allogenic hematopoietic stem cell transplant (HSCT), continued with single agent quizartinib or placebo for up to 36 cycles.

The primary study endpoint is OS. Secondary endpoints include event-free survival (EFS), post-induction rates of complete remission (CR) and composite complete remission (CRc), and the percentage of patients who achieve CR or CRc with FLT3-ITD minimal residual disease negativity. Safety and pharmacokinetics, along with exploratory efficacy and biomarker endpoints, were also evaluated.

QuANTUM-First enrolled 539 patients at approximately 200 study sites worldwide including in Asia, Europe, North America, Oceania and South America. For more information, visit

About Acute Myeloid Leukemia (AML)

More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths.5 AML is one of the most common types of leukemia in adults, representing about one-third of all cases.2 A heterogenous blood cancer, AML is characterized by a five-year survival rate of about 29%, the lowest by far among the major leukemia subtypes.6,7

Treatment guidelines for patients with newly diagnosed AML recommend a cytarabine-based chemotherapy regimen with or without a targeted therapy as determined by the presence of genetic mutations, age and other factors.8 Patients with newly diagnosed FLT3 mutated AML may receive a FLT3 inhibitor as part of their initial treatment regimen and/or subsequent regimens.8 While intensive chemotherapy and/or HSCT can improve chances for sustained remission in eligible patients, a substantial proportion of patients are not suitable for either intervention, and cure rates are particularly low for older patients.1,6 In recent years, new targeted treatments have increased options and improved outcomes for some patients with molecularly defined AML subtypes.6

About FLT3-ITD

FLT3 (FMS-like tyrosine kinase 3) is a transmembrane receptor tyrosine kinase protein normally expressed by hematopoietic stem cells; FLT3 plays an important role in cell development by promoting cell survival, growth and differentiation through various signaling pathways.1 Mutations of the FLT3 gene, which occur in approximately 30% of patients with AML, can drive oncogenic signaling.1 The most common type of FLT3 mutation is the FLT3-ITD (internal tandem duplication), which is present in about 25% of all AML patients and contributes to cancer cell proliferation.1 Patients with FLT3-ITD mutations have a particularly unfavorable prognosis, including an increased risk of relapse and shorter overall survival.1

About Quizartinib

Quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, is in phase 1/2 clinical development in pediatric and young adult patients with relapsed/refractory FLT3-ITD AML in Europe and North America.1 Several phase 1/2 combination studies with quizartinib are also underway at The University of Texas MD Anderson Cancer Center as part of a strategic research collaboration focused on accelerating development of Daiichi Sankyo pipeline therapies for AML.

Quizartinib is currently approved for use in Japan under the brand name VANFLYTA for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, as detected by an approved test. Quizartinib is an investigational medicine in all countries outside of Japan.

About Daiichi Sankyo Oncology

The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.

About Daiichi Sankyo

Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose to contribute to the enrichment of quality of life around the world. In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an Innovative Global Healthcare Company Contributing to the Sustainable Development of Society. For more information, please visit


1 Daver N et al. Leukemia. (2019) 33:299312. 2 American Cancer Society. Key Statistics for Acute Myeloid Leukemia. Updated January 2020. 3 Leukemia and Lymphoma Society. Facts and Statistics. Leukemia: Survival (SEER Data for 2009-2015). 4 Daver N et al. Blood Cancer Journal. (2020) 10:107. 5 Global Cancer Observatory. Population Fact Sheet: World. Updated November 2020. 6 Short et al. Cancer Discov. (2020);10:50625. 7 Leukemia and Lymphoma Society. Facts and Statistics. Leukemia: Survival (SEER Data for 2009-2015). 8 NCCN Practice Guidelines for Oncology. Acute Myeloid Leukemia. Version 3.2021 (March 2, 2021).

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Quizartinib Added to Chemotherapy Demonstrates Superior Overall Survival Compared to Chemotherapy Alone in Adult Patients with Newly Diagnosed...

Researcher awarded $12 million for a stem cell trial to improve outcomes of young blood cancer patients – Stanford Medical Center Report

The California Institute for Regenerative Medicine has awarded nearly $12 million to support a clinical trial of a new cell-based treatment to improve outcomes and survival rates among children and young adults with blood cancer who receive a stem cell transplant.

The treatment, named T-allo10, aims to improve immune responses to pathogens and cancer without increasing the likelihood of graft-versus-host disease in patients who must receive a transplant from an imperfectly matched donor.

The trial will be led by Maria Grazia Roncarolo, MD, professor of pediatrics and of medicine. Roncarolo is the George D. Smith Professor of Stem Cell and Regenerative Medicine, director of the Stanford Center for Definitive and Curative Medicine and co-director of the Institute for Stem Cell Biology and Regenerative Medicine.

Every year around 500 children receive stem cell transplants in California, and while many children do well, too many experience a rejection of the transplant or a relapse of the cancer, Maria Millan, MD, president and CEO of the institute said in a press release. Finding an improved therapy for these children means a shorter stay in the hospital, less risk of the need for a second transplant, and a greater quality of life for the child and the whole family.

The current standard of care for many blood cancers is a two-part treatment of chemotherapy to destroy a patients cancer cells followed by a transplant of blood and immune stem cells from an immunologically matched donor. However, patients sometimes only have the option of receiving a transplant thats a partial immunological match, increasing the risk of graft-versus-host disease, in which the donor immune cells attack the recipients tissues. To reduce this risk, a subset of the donated cells is removed prior to transplant, which in turn increases the chance of a cancer relapse or dangerous infection.

Roncarolo and her team will test T-allo10, in which mature immune cells are concurrently administered with cells called type 1 regulatory T cells, or Tr1 cells, from the donor after a stem cell transplant. The Tr1 cells, which were originally discovered by Roncarolos team, reduce the likelihood that the donors immune cells will perceive the recipients tissue as foreign.

T-allo10 is intended to improve transplant outcomes by reducing cancer recurrence and infection rates, as well as the likelihood of graft-versus-host disease.

My team and I are thrilled to receive CIRMs support for our immunotherapy clinical trial, which may help patients with leukemia receiving a blood stem and progenitor cell transplant fromnonperfectly matched donors a population that continues to suffer poor outcomes and that has high unmet need, Roncarolo said. T-allo10 is unique, as it contains both Tr1 cells, which prevent graft-versus-host disease and rejection, and cells that can fight infections and eliminate residual cancer cells in a single cell product. The development from the bench to the bedside of a Tr1 cell-based product to improve the outcomes of stem cell transplant and induce tolerance is a shining example of the cutting-edge translational work conducted at the Stanford Center for Definitive and Curative Medicine.

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Researcher awarded $12 million for a stem cell trial to improve outcomes of young blood cancer patients - Stanford Medical Center Report

Heart Tissue in a Dish Reveals New Links Between Neurodegeneration and Heart Disease – PRNewswire

Some cases of heart failure have root causes surprisingly similar to diseases like Alzheimers, Huntingtons and ALS.

Over time, sometimes quite rapidly, the heart's thick strong muscle tissue becomes thin and weak, causing the left ventricle to swell like a balloon. This makes the heart less able to squeeze efficiently, which can lead to blood clots, irregular heartbeats, and sometimes sudden death when the malfunctioning heart simply stops beating. The origins of cardiomyopathy are diverse, including viral infections, autoimmune diseases, toxic drug exposures, and dozens of gene mutations.

Now, a multi-disciplinary team of clinicians and researchers has deciphered the function of a specific genetic mutation that causes cardiomyopathy. Their findings,published Nov. 3, 2021, in Nature Communications, were made possible by growing gene-edited human heart tissue from induced pluripotent stem cells and measuring the activity, location and binding of this mutant protein.

The team was led by co-corresponding authors Charles Murry, MD, PhD, a regenerative medicine expert at the University of Washington; Bruce Conklin, MD, a genetic engineering expert with the Gladstone Institutes in California, and Nathan Salomonis, PhD, a computational genomics expert at Cincinnati Children's.

"We hope this study will lead to broader insights that could lead to improved heart failure therapies," Conklin says.

Cutting-edge experiments expose more of the heart's inner workings

Over the last several decades, the research community has made many discoveries that have led to improved medications and medical devices that can dramatically extend life by slowing down the progression of heart failure. However, we still lack proven cures.

This study reveals a new mechanism of cardiomyopathy initiation by the RNA binding motif protein 20 (RBM20). This protein helps control RNA splicing in the heart, the process by which RNAs are sliced and diced to give rise to different proteins in different tissues. Normally, RBM20 splices RNAs to make proteins that enable the heart to adapt to stress and contract regularly throughout a person's entire life. But a class of mutations in RBM20 result in severe cardiomyopathy in adulthood.

"We and others had previously studied RBM20's function during heart development, but we had little to no clue of why it stops working in disease. We needed to step up our game if our research was to have a clinical impact," says Alessandro Bertero, PhD, who contributed to the work while at the University of Washington and now leads an Armenise-Harvard Laboratory at the University of Turin in Italy.

Discovering this protein's role was especially complex because knocking out this gene in animal models does not mimic the damaging effects seen in people. Instead, the work required editing the genome of healthy cells and engineering human heart tissue from these cells in a lab dish. Only by producing heart tissue similar to that found in humans could the authors understand the contractile defects and molecular mechanisms underlying this gene's function in a controlled manner.

"That was exactly what we intended when we started this project by genome-editing induced pluripotent stem cells," says co-leading author Yuichiro Miyaoka, PhD, of the Tokyo Metropolitan Institute of Medical Science.

First, the team observed that the engineered muscle tissue carrying the mutant form of RBM20 did not function like tissue engineered with normal RBM20 or lacking the protein all together. The mutated muscle fibers contracted with significantly less force and upstroke velocity, much like a heart affected by cardiomyopathy.

Then, at the single-cell level, the team detected another important clue. Normally, RBM20 is located exclusively within the cell nucleus. However, the mutated form localizes almost entirely out of the nucleus, in the cell's cytoplasm.

This, by itself, did not mean muchuntil the cell was exposed to heavy stress. When that occurred, the mutant protein was detected within tiny "stress granules" made of protein and RNA that cells rapidly produce as a reaction to stress. In contrast, RBM20 in healthy cells remained within the nucleus and distinct from stress granules. This suggests there are additional cellular mechanisms, along with changes in splice-activity, leading to RBM20 cardiomyopathy.

"When the RNA binding landscape of mutant RBM20 was revealed by a technology called enhanced CLIP, it mimicked the binding of other splicing factors that have been implicated in neurodegenerative diseases. These factors, when mutated, also change their activity from RNA splicing to RNA aggregation outside the nucleus," says co-author Gene Yeo, PhD, MBA, a member of the Department of Cellular and Molecular Medicine at the University of California San Diego.

"Over time, such aggregates play havoc with other cell functions, ultimately leading to the tissue-weakening of heart muscle during cardiomyopathy," Salomonis says.

"It is intriguing to note the parallels between our observations with RBM20 and recent findings in neuro-degeneration," the paper states. "Indeed, recent work has hypothesized cytoplasmic RBM20 may be similar to the cytoplasmic RNP granules associated with neurodegeneration (Schneider et al., 2020), such as TAU for Alzheimer s disease, Huntingtin for Huntington s disease, and FUS for amyotrophic lateral sclerosis (ALS)."

Next steps

Co-authors for this study also included scientists from the University of Cincinnati Department of Electrical Engineering and Computer Science, Sana Biotechnology, and the University of California San Francisco.

The co-authors say the 3D heart tissue model they've developed has the potential to be used to test new drugs to block the formation of cytoplasmic granules as a possible treatment for cardiomyopathy, even those without RBM20 mutations.

"RBM20 has been a frustrating protein to study, as animal models don't fully recapitulate human disease pathology," says lead author Aidan Fenix, PhD. "It's exciting to now have an in vitrohuman cell model of RBM20 cardiomyopathy that shows the major clinical feature of dilated cardiomyopathy--reduced contractile force. We hope these models will speed the discovery of therapies to treat RBM20 dilated cardiomyopathy."

About this study

This work was supported by grants from the National Heart, Lung, and Blood Institute (U01 HL099997, P01 HL089707, R01 HL130533, F32 HL156361-01, HL149734, R01 HL128362, R01 HL128368, R01 HL141570, R01 HL146868); the National Institute of Diabetes and Digestive and Kidney (U54DK107979-05S1); the National Science Foundation (NSF CMMI-1661730); a JSPS Grant-in-Aid for Young Scientists, and grants from NOVARTIS, the Mochida Memorial Foundation, SENSHIN Medical Research Foundation, Naito Foundation, Uehara Memorial Foundation, a Gladstone-CIRM Fellowship, and the A*STAR International Fellowship.

SOURCE Cincinnati Children's Hospital Medical Center

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Heart Tissue in a Dish Reveals New Links Between Neurodegeneration and Heart Disease - PRNewswire

Vaccines less effective at protecting against severe COVID-19 in immunocompromised adults – EurekAlert

INDIANAPOLIS -- New real-world evidence gathered by the U.S. Centers for Disease Control and Prevention (CDC) shows that COVID-19 vaccines are less effective at protecting against COVID-19-associatedhospitalizations in people who are immunocompromised.

In general, immunocompromised individuals are at an increased risk for severe COVID-19 outcomes.

These findings indicate thatwhile two-doses of mRNA COVID-19 vaccines are beneficial inimmunocompromised individuals, theyaresignificantlyless protected from severe disease than people with normal immune systems, said study lead author PeterEmb, M.D., M.S., Regenstrief Institute president and chief executive officer andassociate dean for informatics and health services research at theIndiana UniversitySchool of Medicine. Since they are less protected after a two-dose series, those who are immunocompromisedshould receive an additional dose and a booster, take additional precautions like masking when in public, and, if they get infected, they should seek treatment with proven therapies that can protect against progression to severe disease and the need for hospitalization.

The research team gathered data from more than 89,000 hospitalizations across nine states, making this the largest study of its kind evaluating COVID-19 vaccine effectiveness among immunocompromised people. Data analyses showed that mRNA vaccines (manufactured by Pfizer andModerna) were 90 percent effective at protecting against COVID-related hospitalization in immunocompetent individuals, whereasthey wereonly 77 percent effective in those with suppressed immunity due to a range of health conditions. The differences were similar across age groups. However, the effectiveness varied greatly amongimmunocompromisedsubgroups. For example, it was lower in organ or stem cell transplant patients and better in people with rheumatologic or inflammatory disorders.

Thedata camefrom theVISION Network,a collaboration between the CDC andseven organizationswith integrated medical, laboratory and vaccination records. The network was established to assessthe effectiveness of COVID-19 vaccines.In addition to Regenstrief Institute, other members are Columbia University Irving Medical Center, HealthPartners, Intermountain Healthcare, Kaiser Permanente Northern California, Kaiser Permanente Northwest and University of Colorado.

The paper,Effectiveness of Two-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults nine states, JanuarySeptember 2021, is published in the CDCs Morbidity and Mortality Weekly Report.

Dr.Embis the first author. Other authors from Regenstrief and IU are Shaun Grannis, M.D., M.S.; Brian Dixon, PhD, MPA; William F. Fadel, PhD andNimish R.Valvi, DrPH.

Other authors on the paper areMatthew E. Levy, PhD, ofWestat; Allison L.Naleway, PhD, of Kaiser Permanente Northwest; Palak Patel, MBBS, of the CDC COVID-19 Response Team;ManjushaGaglani, MBBS, of Texas A&M University; Karthik Natarajan, PhD, of Columbia University and New York Presbyterian Hospital; KristinDascomb, M.D., PhD, of Intermountain Healthcare;ToanC. Ong, PhD, of University of Colorado; Nicola P. Klein, M.D., PhD, of Kaiser Permanente Northern California; I-Chia Liao,MPH, of Texas A&M University;JungmiHanof Columbia University; EdwardStenehjem, M.D., of Intermountain Healthcare; Margaret M. Dunne, MSc, ofWestat; Ned Lewis, MPH, of Kaiser Permanente Northern California;Stephanie A. Irving, MHS, ofKaiser Permanente Northwest; Suchitra Rao, MBBS, of University of Colorado; Charlene McEvoy, M.D., of HealthPartners Institute; Catherine H.Bozio, PhD, of the CDC COVID-19 Response Team;KempapuraMurthy, MBBS, of Texas A&M University; Nancy Grisel, MPP, of Intermountain Healthcare; Duck-HyeYang, PhD, ofWestat; Kristin Goddard, MPH, of Kaiser Permanente Northern California; Anupam B. Kharbanda, M.D., of Childrens Minnesota; Sue Reynolds, PhD, of the CDC COVID-19 Response Team; ChandniRaiyani, MPH, of Intermountain Healthcare; JulieArndorfer, MPH, of Intermountain Healthcare; Elizabeth A. Rowley, DrPH, ofWestate; Bruce Fireman, M.A., of Kaiser Permanente Northern California; JillFerdinands, PhD, of the CDC COVID-19 Response Team; Sarah W. Ball, ScD, ofWestat;OussenyZerbo, PhD. Of Kaiser Permanente Northern California; Eric P. Griggs, MPH, of the CDC COVID-19 Response Team; Patrick K. Mitchell, ScD, ofWestate; Rachael M. Porter, MPH, of the CDC COVID-19 Response Team; Salome A.Kiduko, MPH, ofWestat;LeneeBlanton, MPH, of the CDC COVID-19 Response Team; Yan Zhuang, PhDofWestat; Andrea Steffens, MPH, of the CDC COVID-19 Response Team; Sarah E. Reese, PhD, ofWestat; Natalie Olson, MPH, of the CDC COVID-19 Response Team; Jeremiah Williams, MPH, of the CDC COVID-19 Response Team; Monica Dickerson, MPH,of the CDC COVID-19 Response Team; Meredith McMorrow, M.D.of the CDC COVID-19 Response Team; Stephanie J.Schrag, DPhil,of the CDC COVID-19 Response Team; Jennifer R.Verani, M.D.of the CDC COVID-19 Response Team; Alicia M. Fry, M.D.of the CDC COVID-19 Response Team; EduardoAzziz-Baumgartner, M.D.of the CDC COVID-19 Response Team; Michelle A. Barron, M.D., of the University of Colorado; Mark G. Thompson, PhD,of the CDC COVID-19 Response TeamandMalini B. DeSilva, M.D. of HealthPartners Institute.

About Regenstrief Institute

Founded in 1969 in Indianapolis, theRegenstrief Instituteis a local, national and global leader dedicated to a world where better information empowers people to end disease and realize true health. A key research partner to Indiana University, Regenstrief and its research scientists are responsible for a growing number of major healthcare innovations and studies. Examples range from the development of global health information technology standards that enable the use and interoperability of electronic health records to improving patient-physician communications, to creating models of care that inform practice and improve the lives of patients around the globe.

Sam Regenstrief, a nationally successful entrepreneur from Connersville, Indiana, founded the institute with the goal of making healthcare more efficient and accessible for everyone. His vision continues to guide the institutes research mission.

About IU School of Medicine

IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

AboutPeterEmb, M.D., M.S.

In addition to serving as the president and CEO of Regenstrief Institute, PeterEmb, M.D., M.S. is the LeonardBetleyProfessor of Medicine and associate dean for informatics and health services research at Indiana University School of Medicine, associate director of informatics with Indiana Clinical andTranslational Sciences Institute and vice president for Learning Health Systems with Indiana University Health.

Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19Associated Hospitalizations Among Immunocompromised Adults Nine States, JanuarySeptember 2021


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Vaccines less effective at protecting against severe COVID-19 in immunocompromised adults - EurekAlert

Coherus BioSciences Announces CMS Has Extended Enhanced Medicare Reimbursement for UDENYCA in the 340B Hospital Setting Through Year-End 2022 -…

REDWOOD CITY, Calif., Nov. 05, 2021 (GLOBE NEWSWIRE) -- Coherus BioSciences(Coherus, Nasdaq: CHRS), today announced that the Centers for Medicare & Medicaid Services (CMS) will continue to provide increased Medicare reimbursement in the 340B outpatient hospital setting through year-end 2022 for 28 drugs, biologics and devices impacted by the COVID-19 public health emergency, including UDENYCA (pegfilgrastim-cbqv).

We applaud CMS for continuing its support for patients, providers and hospitals impacted by the COVID-19 pandemic, said Denny Lanfear, CEO of Coherus.

After transitional pass-through payment status expires for UDENYCA on March 31, 2022,CMS will provide a separate payment through the end of 2022 to maintain the same reimbursement levels for UDENYCA in the 340B outpatient hospital setting as determined through the pass-through payment program.Pass-through payment status was established by Congress to incentivize access for Medicare patients to biosimilars and other important therapeutics and devices in the hospital outpatient setting. Under the program, reimbursement for UDENYCA in the 340B hospital outpatient setting is calculated at the CMS Average Sales Price (ASP) for UDENYCA plus 6% of the ASP for Neulasta (pegfilgrastim). By comparison, Neulasta is currently reimbursed in the 340B hospital setting at the Neulasta ASP less 22.5%.

About UDENYCA UDENYCA is the #1 prescribed pegfilgrastim pre-filled syringe in the United States.

UDENYCAis a leukocyte growth factor indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Limitations of Use: UDENYCAis not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Contraindications: Patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products. Reactions have included anaphylaxis

Warnings and Precautions:

Fatal splenic rupture:Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue UDENYCAin patients with ARDS.

Serious allergic reactions, including anaphylaxis: The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue UDENYCAin patients with serious allergic reactions.

Sickle cell crises:Severe and sometimes fatal crises have occurred. Discontinue UDENYCAif sickle cell crisis occurs.

Glomerulonephritis:The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events resolved after dose reduction or discontinuation. Evaluate and consider dose-reduction or interruption of UDENYCAif causality is likely.

Leukocytosis:White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim products. Monitoring of complete blood count (CBC) during UDENYCAtherapy is recommended.

Thrombocytopenia:Thrombocytopenia has been reported in patients receiving pegfilgrastim. Monitor platelet counts.

Capillary Leak Syndrome:Has been reported after G-CSF administration, including pegfilgrastim products, and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. If symptoms develop, closely monitor and give standard symptomatic treatment, which may include a need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells:The possibility that pegfilgrastim products act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded.

Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer:MDS and AML have been associated with the use of pegfilgrastim in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for sign and symptoms of MDS/AML in these settings.

Aortitis:Has been reported in patients receiving pegfilgrastim products, occurring as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis when signs and symptoms develop without known etiology. Discontinue UDENYCA if aortitis is suspected.

Nuclear Imaging:Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. Consider when interpreting bone imaging results.

Adverse Reactions:Most common adverse reactions ( 5% difference in incidence compared to placebo) are bone pain and pain in extremity.

To report SUSPECTED ADVERSE REACTIONS, contactCoherus BioSciencesat 1-800-4-UDENYCA (1-800-483-3692)orFDAat 1-800-FDA-1088

Full Prescribing Information available

About Coherus BioSciences

Coherus is a commercial stage biopharmaceutical company with the mission to increase access to cost-effective medicines that can have a major impact on patients lives and to deliver significant savings to the health care system. Coherus strategy is to build a leading immuno-oncology franchise funded with cash generated by its commercial biosimilar business. For additional information, please visit

Coherus markets UDENYCA (pegfilgrastim-cbqv) in the United States and through 2023 expects to launch toripalimab, an anti-PD-1 antibody, as well as biosimilars of Lucentis, Humira, and Avastin, if approved.

UDENYCA is a trademark of Coherus BioSciences, Inc.

Neulasta is a registered trademark of Amgen, Inc.

Avastin and Lucentis are registered trademarks of Genentech, Inc.

Humira is a registered trademark of AbbVie Inc.

Forward-Looking Statements

Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, Coherus ability to generate cash flow from its UDENYCA business; the reimbursement of UDENYCA by CMS in the 340B hospital at the rate of UDENYCA Average Sale Price + 6% of the Neulasta ASP through year-end 2022; Coherus plans to invest the cash generated by its biosimilar commercial business to build a focused immuno-oncology franchise; Coherus ability to prepare for projected launches through 2023 of toripalimab or of biosimilars of Humira, Avastin and Lucentis, if approved.

Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus actual results, performance or achievements to differ significantly from any future results, performance or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the clinical drug development process; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus regulatory filings; the risk of FDA review issues; the risk that Coherus is unable to complete commercial transactions and other matters that could affect the availability or commercial potential of Coherus drug candidates; and the risks and uncertainties of possible patent litigation. All forward-looking statements contained in this press release speak only as of the date on which they were made. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus business in general, see Coherus Annual Report on Form 10-K for the year ended December 31, 2020, filed with the Securities and Exchange Commission on February 25, 2021,its Quarterly Report on Form 10-Q for the three and six months ended June 30, 2021, filed with the Securities and Exchange Commission on August 5, 2021 and its future periodic reports to be filed with the Securities and Exchange Commission. Results for the quarter ended June 30, 2021 are not necessarily indicative of our operating results for any future periods.

Coherus Contact Information: IR Contact: Cheston Turbyfill Coherus BioSciences, Inc.

Coherus BioSciences Announces CMS Has Extended Enhanced Medicare Reimbursement for UDENYCA in the 340B Hospital Setting Through Year-End 2022 -...

Precision BioSciences Announces Two Oral Presentations Highlighting Updated Interim Data from Lead PBCAR0191 CAR T Immunotherapy for Relapsed and…

- Enhanced Lymphodepletion Improved Overall Response Rate and Complete Response Rate Compared to Standard Lymphodepletion in Heavily Pretreated NHL and B-ALL Subjects with a Median of ~6 Prior Lines of Therapy

- Clinically Significant Activity in Subjects Previously Treated with Autologous CD19 Directed CAR T

- In B-ALL Subjects Enhanced Lymphodepletion or Higher Doses of PBCAR0191 Resulted in High Complete Response Rates Allowing the Potential to Bridge to Allogeneic Stem Cell Transplant

- Data Presented at ASH will be Updated to Include Subjects with >28 Day Follow up as of October 10, 2021

DURHAM, N.C., November 04, 2021--(BUSINESS WIRE)--Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company using its ARCUS genome editing platform to develop allogeneic CAR T and in vivo gene editing therapies, today announced that investigators involved with the Phase 1/2a study of PBCAR0191 in Relapsed/Refractory (R/R) non-Hodgkins lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL), will present new data during two oral presentations at the 63rd Annual Meeting of the American Society of Hematology (ASH) taking place December 11-14, 2021.

"We are encouraged by the response rates seen in this heavily pre-treated patient population, and that a treatment strategy with enhanced lymphodepletion mitigated PBCAR0191 rejection and improved peak CAR T cell expansion and persistence, compared to standard lymphodepletion, with predictable toxicity," said Alan List, MD, Chief Medical Officer of Precision BioSciences. "We look forward to sharing additional patient outcome, durability, and safety data for PBCAR0191 at the American Society of Hematology Annual Meeting."

The abstracts accepted by the ASH are now available at, and will be presented during the following oral presentation sessions:

Session Name: 626, Abstract #302. Aggressive Lymphomas Prospective Therapeutic Trials: Challenging Populations Oral Presentation Title: Allogeneic CAR-T PBCAR0191 with Intensified Lymphodepletion is Highly Active in Subjects with Relapsed/Refractory B-cell Malignancies Presenting Author: Bijal Shah, M.D., Moffitt Cancer Center Date/Time: Saturday, December 11, 2021 at 4:15 PM ET Location: Georgia World Congress Center, B401-B402

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Session Name: 704, Abstract #650 Cellular Immunotherapies: Allogeneic CARs and CARs for T Cell Lymphomas Oral Presentation Title: Preliminary Safety and Efficacy of PBCAR0191, an Allogeneic Off-the-Shelf CD19-Directed CAR-T for Patients with Relapsed/Refractory (R/R) CD19+ B-ALL Presenting Author: Nitin Jain, M.D., The University of Texas MD Anderson Cancer Center Date/Time: Monday, December 13, 2021 at 10:45 AM ET Location: Georgia World Congress Center, Sidney Marcus Auditorium

Published abstracts report on key interim clinical evaluations of CD19+ NHL or B-ALL subjects treated with PBCAR0191.

Abstract #302: For 21 subjects with Relapsed/Refractory (R/R) B-cell malignancies (16 NHL, 5 B-ALL) who received PBCAR0191 following enhanced lymphodepletion1 as of July 1, 2021:

PBCAR0191 demonstrated a safety profile with no Grade 3 CRS, one Grade 3 self-limited ICANS, no evidence of GvHD, and one infectious death at Day 54, deemed possibly related to treatment.

83% (15/18) of evaluable subjects experienced a complete response (CR) rate or complete remission with incomplete marrow recovery (CRi); 62% (8/13) of NHL subjects and 80% (4/5) of B-ALL subjects, respectively.

20% (3/15) of responders demonstrated durability of response greater than 6 months, with 3 additional responders not yet having reached a 6-month evaluation threshold.

Compared to standard lymphodepletion2, enhanced lymphodepletion mitigated PBCAR0191 rejection to markedly improve peak CAR T cell expansion and persistence with area under the curve increasing 80-fold.

Among 6 subjects who progressed following prior CD19 CAR therapy (5 NHL, 1 B-ALL), the overall response rate was 83% (5/6) with 67% (4/6) achieving a CR, including an ongoing MRD negative CR in a B-ALL subject of >6 months.

Abstract #650: For 15 subjects with R/R B-cell acute lymphoblastic leukemia including 11 subjects who received PBCAR0191 Dose Level 3/4a3 and 4 subjects who received PBCAR0191 Dose Level 4b4 as of August 2, 2021:

PBCAR0191 demonstrated a safety profile with no cases of GvHD, no Grade 3 CRS, and one case of Grade 3 ICANS, which resolved within 48 hours.

For subjects who received either Dose Level 3/4a following enhanced lymphodepletion or Dose Level 4b following standard lymphodepletion, 78% (7/9) achieved a high CR or CRi rate; 56% (5/9) maintained the CR at day 28 or later potentially securing an adequate window to bridge to allogeneic stem cell transplant.

Use of enhanced lymphodepletion or higher doses of PBCAR0191 resulted in substantial improvements in peak CAR T cell expansion and area under the curve.

About Precision BioSciences, Inc.

Precision BioSciences, Inc. is a clinical stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS genome editing platform. ARCUS is a highly specific and versatile genome editing platform that was designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the Companys pipeline consists of multiple "off-the-shelf" CAR T immunotherapy clinical candidates and several in vivo gene editing candidates designed to cure genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding our clinical development pipeline and interim data announcements. In some cases, you can identify forward-looking statements by terms such as "aim," "anticipate," "believe," "could," "expect," "should," "plan," "intend," "estimate," "target," "mission," "goal," "may," "will," "would," "should," "could," "target," "potential," "project," "predict," "contemplate," "potential," or the negative thereof and similar words and expressions. Forward-looking statements are based on managements current expectations, beliefs and assumptions and on information currently available to us. Such statements are subject to a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to: our ability to become profitable; our ability to procure sufficient funding and requirements under our current debt instruments and effects of restrictions thereunder; risks associated with raising additional capital; our operating expenses and our ability to predict what those expenses will be; our limited operating history; the success of our programs and product candidates in which we expend our resources; our limited ability or inability to assess the safety and efficacy of our product candidates; our dependence on our ARCUS technology; the initiation, cost, timing, progress, achievement of milestones and results of research and development activities, preclinical or greenhouse studies and clinical or field trials; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, biotechnology and agricultural biotechnology fields; our or our collaborators ability to identify, develop and commercialize product candidates; pending and potential liability lawsuits and penalties against us or our collaborators related to our technology and our product candidates; the U.S. and foreign regulatory landscape applicable to our and our collaborators development of product candidates; our or our collaborators ability to obtain and maintain regulatory approval of our product candidates, and any related restrictions, limitations and/or warnings in the label of an approved product candidate; our or our collaborators ability to advance product candidates into, and successfully design, implement and complete, clinical or field trials; potential manufacturing problems associated with the development or commercialization of any of our product candidates; our ability to obtain an adequate supply of T cells from qualified donors; our ability to achieve our anticipated operating efficiencies at our manufacturing facility; delays or difficulties in our and our collaborators ability to enroll subjects; changes in interim "top-line" and initial data that we announce or publish; if our product candidates do not work as intended or cause undesirable side effects; risks associated with applicable healthcare, data protection, privacy and security regulations and our compliance therewith; the rate and degree of market acceptance of any of our product candidates; the success of our existing collaboration agreements, and our ability to enter into new collaboration arrangements; our current and future relationships with and reliance on third parties including suppliers and manufacturers; our ability to obtain and maintain intellectual property protection for our technology and any of our product candidates; potential litigation relating to infringement or misappropriation of intellectual property rights; our ability to effectively manage the growth of our operations; our ability to attract, retain, and motivate key executives and personnel; market and economic conditions; effects of system failures and security breaches; effects of natural and manmade disasters, public health emergencies and other natural catastrophic events effects of the outbreak of COVID-19, or any pandemic, epidemic or outbreak of an infectious disease; insurance expenses and exposure to uninsured liabilities; effects of tax rules; risks related to ownership of our common stock and other important factors discussed under the caption "Risk Factors" in our Quarterly report on Form 10-Q for the quarterly period ended June 30, 2021, as any such factors may be updated from time to time in our other filings with the SEC, which are accessible on the SECs website at and the Investors & Media page of our website at

All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we have no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

1 eLD = Fludarabine (30 mg/m/day for 4 days) and cyclophosphamide (1000 mg/m2/day for 3 days) 2 sLD = Fludarabine (30 mg/m/day for 3 days) and cyclophosphamide (500 mg/m2/day for 3 days) 3 3 x 10 cells/kg or equivalent following either standard or enhanced lymphodepletion 4 Flat dose of 5 x 10 cells following standard lymphodepletion

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Precision BioSciences Announces Two Oral Presentations Highlighting Updated Interim Data from Lead PBCAR0191 CAR T Immunotherapy for Relapsed and...

All you need to know about the COVID boosters available in Somerset County – Daily American Online

By Judy D.J. Ellich | For the Daily American

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CDC panel backs booster expansion despite concerns

Federal health officials say millions more Americans can get a COVID-19 booster and choose a different vaccine for that shot. The FDA authorized such an expansion of the nations booster campaign, also endorsed Thursday by a CDC advisory panel. (Oct. 21)


Booster shots against COVID-19 are now available.

And members ofthree regional health care systems and the Cambria/Somerset COVID-19 Task Force are discussingthese vaccines, who should receive them and where to get them.

"The most important thing is that people get vaccinated, and we encourage them to do it as soon as possible," said David Bertoty, director of emergency services atUPMC Somerset. "Vaccines are safe and very effective at preventing serious illness. The vaccine is still protecting against serious illness, six to eight months after full vaccination.

"The booster reinforces the immunity that you have. For those who are immunocompromised, the booster may also be impactful if they didnt develop a response in the first place," he said.

Boosters are tobe available at UPMC Somerset's regularly scheduled clinics, which are from noon to 4:45 p.m. Mondays and Thursdays.

A trend: Ivermectin: A trend in fighting COVID-19, but does it do the job?

Best defense: Pregnant? Many doctors say COVID vaccine 'best line of defense' against complications

Another way:Local mom-and-daughter team take COVID vaccines on the road in Somerset County

UPMC Somerset is currently administering the Pfizer boosterfor immunocompromised people. Hospital officialsanticipate being able to administer the Moderna and Johnson & Johnson boosters in the near future, Bertoty said.

The health care systemrecommends that people register in advance to receive a vaccine at Walk-ins are also accepted.

"People should bring their vaccination cards with them so they can be updated," he said.

The Moderna and Pfizer boosters are recommended for individuals meeting the following criteria at least six months after their second dose:

The Johnson & Johnson booster has been recommended for all individuals 18 and olderat least two months after their first dose.

Chan Soon-Shiong Medical Center has administered approximately 1,500 booster doses of the Pfizer COVID-19 vaccine thus far, according to Dr. David Csikos, chief medical officer.

"Experts do not know how long someone is protected from getting sick again after recovering from COVID-19. The immunity someone gains from having an infection, called 'natural immunity,'varies from person to person. Also, the effectiveness of natural immunity against variant strains is unknown," he said."Re-infection is uncommon within 90 days following initial infection, however re-infection is possible."

"Due to the severe health risks associated with COVID-19, and the fact that re-infection is possible, patients should be vaccinated regardless of whether they have already had COVID-19 infection."

The Windber health care system provides avaccine clinic every Wednesday at the hospital. To schedule a booster dose of the Pfizer vaccine, adults are asked to call 814-467-3013.

In addition, the medical center plans to hold a Saturday vaccine clinic Nov. 13.Chan Soon-Shiong Medical Center also continues to vaccinate at schools, personal care and other facilities, including Roxbury Place and Quemahoning Towers.

COVID-19 vaccine booster shots are available for the following Pfizer vaccine recipients who completed their initial series at least 6 months ago and are:

Those who were treated for COVID-19 symptoms with monoclonal antibodies or convalescent plasma should wait 90 days before getting a COVID-19 vaccine.

Conemaugh Memorial Medical Center recently hosted two community clinics for approximately 1,000 individuals. These openings filled upquickly.

"Conemaugh Health System strongly encourages individuals who have already completed a two-dose vaccination series (Pfizer or Moderna) or the single-dose regimen (J&J/Janssen) to get their booster shot if/when they meet the specific clinical and time frame criteria," saidKristen Hudak, marketing communications director atConemaugh Health System.

"We continue to offer booster doses to our employees, and we are evaluating whether additional dates for community clinics are necessary at this time."

COVID-19 vaccinations including boosters are covered by insurance and are free to all individuals, regardless of their insured status.

Vaccine providers on the task force have encountered the following questions from local residents.

For the nearly 15 million people who got the Johnson & Johnson COVID-19 vaccine, booster shots are also recommended for those who are 18 and older and who were vaccinated two or more months ago.

The Centers for Disease Control and Prevention recommends thatthose with moderately to severely compromised immune systemsreceive an additional dose of a mRNA COVID-19 vaccine at least 28 days after a second dose of the Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine.

Theadditional dose is intended to improve immunocompromised peoples response to their initial vaccine series. This includes people who have:

People are encouraged to talk to their health care provider about their medical condition, and whether receivingan additional dose is appropriate for them. Everyone is considered fully vaccinated two weeks after their second dose in a two-shot series or two weeks after a single-dose vaccine.

According to Jeannine McMillan, executive director of 1889 Jefferson Center for Population Health, patients need to bring their vaccination cards to an appointment for a booster shot.

If the card is lost or misplaced,contact the vaccine provider directly to access thevaccination record, she said.If the provider cannot be contacted, reach out tothe state Department of Health immunization information system at 877-774-4748.

If one hasmade every effort and still cannot locate your vaccine information, McMillan said, talk to a vaccine provider.

A full list of providers is available at or by calling 1-800-232-0233 or 888-720-7489.

Some local providers numbers and websites other than the three health care systems already listed are as follows:

Total cases: 10,701.

Deaths: 253.

COVID-19 patients hospitalized: 25.

COVID-19 patients (adult) in ICU: 0.

COVID-19 patients on ventilators: 0.

Partially vaccinated: 3,093.

Fully vaccinated: 30,635.

Total cases: 19,633.

Deaths: 513.

COVID-19 patients hospitalized: 54.

COVID-19 patients (adult) in ICU: 11.

COVID-19 patients on ventilators: 11.

Partially vaccinated: 5,490.

Fully vaccinated: 62,408.

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All you need to know about the COVID boosters available in Somerset County - Daily American Online

Asia-Pacific Cell Therapy Market 2021-2028 – Opportunities in the Approval of Kymriah and Yescarta – PRNewswire

DUBLIN, Aug. 4, 2021 /PRNewswire/ -- The "Asia Pacific Cell Therapy Market Size, Share & Trends Analysis Report by Use-type (Clinical-use, Research-use), by Therapy Type (Autologous, Allogeneic) and Segment Forecasts, 2021-2028" report has been added to's offering.

The Asia Pacific cell therapy market size is expected to reach USD 2.9 billion by 2028. The market is expected to expand at a CAGR of 14.9% from 2021 to 2028.

Rapid advancements in regenerative medicine are anticipated to provide effective solutions for chronic conditions. A substantial number of companies in the growing markets, such as India and South Korea, are striving to capitalize on the untapped opportunities in the market, thereby driving the market.

The growth is greatly benefitted by the fund and regulatory support from government bodies and regulatory agencies. For instance, in August 2020, the government of South Korea passed an Act on the Safety and Support of Advanced Regenerative Medical Treatment and Medicine to establish a regulatory system for patient safety during quality control and clinical trials and to strengthen the regulatory support for regenerative medicine development.

The implementation of the act is expected to enhance clinical studies and approvals of regenerative medicine in South Korea. Furthermore, CAR-T and TCR T-cell therapies have already revolutionized hematologic cancer treatment. With the onset of the COVID-19 pandemic, scientists are deciphering its potential against the novel coronavirus. The concept of using T cells against chronic viral infections, such as HIV and hepatitis B, has already been proposed.

Based on the previous research insights, Singapore-based Duke-NUS medical school's emerging infectious diseases research program demonstrated the utility of these immunotherapies in treating patients with COVID-19 infection.

Thus, an increase in research for use of cell therapies for COVID-19 treatment is expected to drive the market in Asian countries. In April 2021, a team of researchers from Japan used induced pluripotent stem cells (iPS) to find drugs that can effectively inhibit the coronavirus and other RNA viruses.

Key Topics Covered:

Chapter 1 Methodology and Scope

Chapter 2 Executive Summary 2.1 Market Snapshot

Chapter 3 Cell Therapy Market Variables, Trends, and Scope 3.1 Market Trends and Outlook 3.2 Market Segmentation and Scope 3.3 Market Dynamics 3.3.1 Market driver analysis Rise in number of clinical studies for cellular therapies in Asia Pacific Expanding regenerative medicine landscape in Asian countries Introduction of novel platforms and technologies 3.3.2 Market restraint analysis Ethical concerns Clinical issues pertaining to development & implementation of cell therapy Manufacturing issues Genetic instability Condition of stem cell culture Stem cell distribution after transplant Immunological rejection Challenges associated with allogeneic mode of transplantation 3.3.3 Market opportunity analysis Approval of Kymriah and Yescarta across various Asian countries Developments in CAR T-cell therapy for solid tumors 3.3.4 Market challenge analysis Operational challenges associated with cell therapy development & usage Volume of clinical trials for cell and gene therapy vs accessible qualified centers Complex patient referral pathway Patient treatment, selection, and evaluation Availability of staff vs volume of cell therapy treatments 3.4 Penetration and Growth Prospect Mapping for Therapy Type, 2020 3.5 Business Environment Analysis 3.5.1 SWOT Analysis; By factor (Political & Legal, Economic and Technological) 3.5.2 Porter's Five Forces Analysis 3.6 Regulatory Framework 3.6.1 China Regulatory challenges & risk of selling unapproved cell therapies 3.6.2 Japan

Chapter 4 Cell Therapy Market: COVID-19 Impact analysis 4.1 Challenge's analysis 4.1.1 Manufacturing & supply challenges 4.1.2 Troubleshooting the manufacturing & supply challenges associated to COVID-19 4.2 Opportunities analysis 4.2.1 Need for development of new therapies against SARS-CoV-2 Role of T-cell based therapeutics in COVID-19 management Role of mesenchymal cell-based therapeutics in COVID-19 management 4.2.2 Rise in demand for supply chain management solutions 4.3 Challenges in manufacturing cell therapies against COVID-19 4.4 Clinical Trial Analysis 4.5 Key Market Initiatives

Chapter 5 Asia Pacific Cell Therapy CDMOs/CMOs Landscape 5.1 Role of Cell Therapy CDMOs 5.2 Key Trends Impacting Asia Cell Therapy CDMO Market 5.2.1 Regulatory reforms 5.2.2 Expansion strategies 5.2.3 Rising investments 5.3 Manufacturing Volume Analysis 5.3.1 Wuxi Biologics 5.3.2 Samsung Biologics 5.3.3 GenScript 5.3.4 Boehringer Ingelheim 5.3.5 Seneca Biopharma, Inc. 5.3.6 Wuxi AppTech 5.4 Competitive Milieu 5.4.1 Regional network map for major players

Chapter 6 Asia Pacific Cell Therapy Market: Use Type Business Analysis 6.1 Market (Stem & non-stem cells): Use type movement analysis 6.2 Clinical Use 6.2.1 Market (stem & non-stem cells) for clinical use, 2017 - 2028 (USD Million) 6.2.2 Market (stem & non-stem cells) for clinical use, by therapeutic area Malignancies Market (stem & non-stem cells) for malignancies, 2017 - 2028 (USD Million) Musculoskeletal disorders Autoimmune disorders Dermatology 6.2.3 Market (stem & non-stem cells) for clinical use, by cell type Stem cell therapies Market, 2017 - 2028 (USD Million) BM, blood, & umbilical cord-derived stem cells/mesenchymal stem cells Adipose-derived stem cell therapies Other stem cell therapies Non-stem cell therapies 6.3 Research Use

Chapter 7 Asia Pacific Cell Therapy Market: Therapy Type Business Analysis 7.1 Market (Stem & Non-stem Cells): Therapy type movement analysis 7.2 Allogeneic Therapies 7.3 Autologous Therapies

Chapter 8 Asia Pacific Cell Therapy Market: Country Business Analysis 8.1 Market (Stem & Non-stem Cells) Share by Country, 2020 & 2028

Chapter 9 Asia Pacific Cell Therapy Market: Competitive Landscape

For more information about this report visit

Media Contact: Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1904 Fax (outside U.S.): +353-1-481-1716

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Asia-Pacific Cell Therapy Market 2021-2028 - Opportunities in the Approval of Kymriah and Yescarta - PRNewswire

Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of … – The Bakersfield Californian

Off-the-Shelf CAR T-cell Product Candidate Derived from Clonal Master iPSC Line with Novel CD19-specific 1XX CAR Integrated into TRAC Locus

Phase 1 Clinical Study will Evaluate Three Dosing Regimens of FT819 for Patients with Advanced B-cell Leukemias and Lymphomas

SAN DIEGO, Aug. 02, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, announced today that the first patient has been treated with FT819, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies. FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of high quality, allogeneic CAR T cells with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy.

Remarkable clinical outcomes have been achieved through treatment with patient-derived CAR T-cell therapy, however, next-generation approaches are necessary to reach more patients who are in need of these highly-effective therapies, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Treatment of the first-ever patient with FT819 ushers in a new era for off-the-shelf CAR T-cell therapy, with the potential to overcome the real-world limitations of existing patient- and donor-derived therapeutic approaches and unlock the full potential of CAR T-cell therapy. We would like to thank our collaborators at Memorial Sloan Kettering Cancer Center, whose partnership over the past five years has profoundly contributed to this landmark achievement.

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, the Company incorporated several first-of-kind features into FT819 including:

Use of a clonal master engineered iPSC line as the starting cell source, which enables CAR T cells to be mass produced and delivered off-the-shelf for broad patient access;Incorporation of a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion as described in the journal Nature Medicine (

);Insertion of the CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T-cell potency as described in the journal Nature (https://

); andComplete bi-allelic disruption of T-cell receptor (TCR) expression for the prevention of graft-versus-host disease (GvHD), a potentially life-threatening complication associated with allogeneic T-cell therapy.

The multi-center Phase 1 clinical trial of FT819 is designed to determine the recommended Phase 2 dose and schedule of FT819 and assess its safety and clinical activity in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphomas (BCL). Three treatment regimens will be independently evaluated for each type of malignancy in dose escalation: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts may be enrolled to further evaluate the clinical activity of FT819. The first patient with relapsed / refractory ALL was enrolled in Regimen A and received a dose of 90 million cells.

At the 24th American Society of Gene & Cell Therapy Annual Meeting held in May 2021, the Company presented preclinical data demonstrating that FT819 exhibits uniform 1XX CAR expression with complete elimination of endogenous TCR expression. The product candidate was shown to contain a stem- and central-memory T-cell phenotype, and had high-level expression of the activation marker CD25 and the trafficking marker CXCR4 and very low-level expression of the checkpoint proteins PD1, TIM3, CTLA4 and LAG3. Additionally, data from functional assessments showed that FT819 had potent antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of healthy donor-derived CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics haslicensedintellectual propertyfrom MSK on which Dr. Sadelain is aninventor.As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics iPSC Product Platform The Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT819 FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit

Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of, plans related to, and the therapeutic potential of the Company's product candidates, the Companys clinical development and manufacturing strategies, and the Companys plans for the clinical investigation and manufacture of its product candidates, including FT819. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that the Company may cease or delay clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact: Christina Tartaglia Stern Investor Relations, Inc. 212.362.1200

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Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of ... - The Bakersfield Californian

IDH1 Inhibitors, CAR T-Cell Therapy, and Third-Generation TKIs Refresh Relapsed/Refractory Leukemia Landscape – OncLive

Acute Myeloid Leukemia

Historical complete response (CR)/CR with incomplete hematologic recovery rates with approved IDH inhibitors, enasidenib (Idhifa) and ivosidenib (Tibsovo), hover around 30% and have a median overall survival (OS) of approximately 9 months in the relapsed/refractory setting, said Shammo, a professor of medicine and pathology at Rush University Medical Center, in a virtual presentation during the2021 ASCO Direct HighlightsTMwebcast in Chicago, a program developed by Physicians Education Resource LLC.

Olutasidenib, a highly potent, orally active, selective IDH1 inhibitor, was developed to improve outcomes in the 7% to 14% of patients with AML who harbor IDH1 mutations.

In the phase 1/2 2102-HEM-101 trial (NCT02719574), 150 mg of oral olutasidenib was evaluated as a single agent and in combination with azacitidine across 8 cohorts of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes. Findings from the planned interim analysis, which were presented during the 2021 ASCO Annual Meeting, focused on cohort 1, which enrolled 153 patients with relapsed/refractory, IDH1-mutant AML.1

In the efficacy-evaluable population (n = 123), 37% of patients had secondary AML, 73% of patients had intermediate cytogenetic risk, 44% of patients were refractory to their last line of therapy, and 11% had failed allogeneic stem cell transplant, reflecting a difficult population to treat, said Shammo.

The primary end point, CR/CR with partial hematologic recovery (CRh), was 33% (95% CI, 25.1%-42.4%), and most CR/CRh responders had a CR (30%; 95% CI, 22.1%-39.0%).

Transfusion independence was achieved in all response groups, particularly those achieving a CR, said Shammo.

The agent also demonstrated durable CR/CRh benefit, with a median duration of CR/CRh that was not reached and a median duration of response (DOR) of 11.7 months. In a sensitivity analysis with transplant considered as the end of a response, the median duration of CR/CRh response was 13.8 months.

Those who responded well had a much longer DOR, and a fraction of those patients managed to go onto stem cell transplant, which is what you would like to do in relapsed/refractory AML, said Shammo.

Better response was strongly associated with longer survival as well. At a median follow-up of 9.7 months, the median OS was not reached in patients who had achieved a CR/CRh, with an estimated 18-month OS rate of 87%. In the safety population (n = 153), the median OS was 10.5 months (95% CI, 7.7-15.5). Among nonCR/CRh responders and non-responders, the median OS was 15.0 months (95% CI, 5.0not evaluable) and 4.1 months (95% CI, 3.2-5.8), respectively.

Clinical benefit, as evidenced by DOR and OS, extended to patients who responded but did not achieve CR/CRh, said Shammo.

The primary treatment-emergent adverse effects (AEs) included leukocytosis (all-grade, 25%; grade 3/4, 9%) and febrile neutropenia (all-grade, 22%; grade 3/4, 20%), said Shammo. AEs of special interest reflected reports of differentiation syndrome (all-grade, 14%; grade 3/4, 7%), QTc prolongation (all-grade, 8%; grade 3/4, <1%), and liver abnormalities (all-grade, 21%; grade 3/4, 10%).

Olutasidenib was well tolerated with a safety profile largely consistent with that of other IDH inhibitors, but patients should be monitored for differentiation syndrome and liver abnormalities, said Shammo.

These results are very promising and very impressive, and, hopefully, we will see more results not only with the single agent but also with the combination with azacitidine in other myeloid malignancies, added Shammo.

Turning to acute lymphoblastic leukemia (AML), Shammo discussed the results of the phase 1/2 ZUMA-3 trial (NCT02614066), which evaluated the CD19-directed chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel in patients with relapsed/refractory ALL.2

Approximately 40% to 50% of adults with B-ALL experience relapse after initial treatment, with a 1-year OS rate of 26% after first salvage therapy, said Shammo in explaining the rationale for the study.

In the phase 1 portion of the study, brexucabtagene autoleucel demonstrated a CR/CRi rate of 83% and manageable safety profile. In the phase 2 portion, 71 patients were enrolled, and 55 patients received brexucabtagene autoleucel.

Patients could have received prior treatment with blinatumomab (Blincyto) and underwent conditioning chemotherapy with fludarabine and cyclophosphamide prior to treatment with the recommended phase 2 dose of brexucabtagene autoleucel: 1 x 106 CAR T cells/kg.

Brexucabtagene autoleucel was successfully manufactured in 92% of patients, and the median time from leukapheresis to manufacturing release was 13 days for patients in the United States, which Shammo called remarkable.

Regarding baseline demographics, 27% of patients had Philadelphia chromosomepositive disease, 100% of which had central nervous system disease at baseline, and 47% of patients had received at least 3 lines of prior therapy.

Additionally, 45% of patients received prior blinatumomab, 42% underwent prior allogeneic transplant, and the median blast count was 65.0 and 59.0 at screening and preconditioning after bridging chemotherapy, respectively.

At a median follow-up of 16.4 months, the primary end point of CR/CRi rate by central assessment, was 70.9% (CR, 56.4%; CRi, 14.5%); 31% of responders were in ongoing remission at the data cutoff.

[We saw] a high and durable response rate in heavily pretreated adults with relapsed/refractory B-ALL, most of whom had high disease burden, said Shammo.

The median time to initial CR/CRi was 1.1 months. The minimal residual disease (MRD)negativity rate was 97% in responders, and 10 patients, including 9 with CR/CRi and 1 with blast-free hypoplastic or aplastic bone marrow underwent allogeneic transplant a median of 98 days (range, 60-207) following CAR T-cell infusion.

This is exactly what you would like to do: induce patients into remission to take them to allogeneic transplant, said Shammo. Whats remarkable is that MRD negativity in patients who had this treatment approximated 100%.

Among patients with CR/CRi (n = 39), the median OS was not reached (95% CI, 16.2-NE) and the median relapse-free survival (RFS) was 14.2 months (95% CI, 11.6-NE). All-treated patients (n = 39) had a median OS and RFS of 18.2 months (95% CI, 15.9-NE) and 11.6 months (95% CI, 2.7-15.5) respectively. Non-CR/CRi responders (n = 16) had a median OS and RFS of 2.4 months (95% CI, 0.7-NE) and 0.0 months (95% CI, NE-NE), respectively.

Regarding safety, any-grade cytokine release syndrome (CRS) occurred in 89% of patients, and grade 3 or higher CRS occurred in 24% of patients, with a median onset of 5 days and manifestation of pyrexia and hypotension.

Thats relatively favorable compared with what you might expect with [CAR T-cell therapy], said Shammo.

No cases of grade 5 CRS were reported, although 1 patient had grade brain herniation related to study treatment.

Any-grade neurologic events were reported in 60% of patients, and grade 3 or greater events occurred in 25% of patients, with a median onset of 9 days and manifestation of tremor and confused state.

Tocilizumab (Actemra), steroids, and vasopressors were given to 80%, 75%, and 40% of patients, respectively.

The safety profile was manageable, and AEs were largely reversible, said Shammo. The efficacy, rapid manufacturing, and manageable safety support the promising potential of brexucabtagene autoleucel to provide long-term clinical benefit in adults with relapsed/refractory B-ALL.

On April 2, 2021, a supplemental biologics license application was submitted to the FDA for brexucabtagene autoleucel as a treatment for adult patients with relapsed/refractory B-cell precursor ALL.3

If approved, brexucabtagene autoleucel would become the first and only CAR T-cell therapy approved for adults aged at least 18 years old with relapsed/refractory ALL.

The final study Shammo highlighted was the phase 2 OPTIC trial (NCT02467270), which evaluated 3 daily starting doses of ponatinib45 mg (n = 93), 30 mg (n = 93), and 15 mg (n = 91)in patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to a prior second-generation BCR-ABL1 TKI inhibitor or with a T315I mutation.4

Patients in the 45-mg and 35-mg arms were dose reduced to 15 mg daily upon achievement of 1% or less BCR-ABL1 and across arms were dose reduced to 10 mg daily in the presence of AEs.

Ponatinib, the only pan-BCR-ABL1 inhibitor, is a third-generation TKI designed to inhibit BCR-ABL1 with or without any single resistance mutation, including T315I.

In the pivotal, phase 2 PACE trial (NCT01207440), ponatinib demonstrated deep and durable responses to 45 mg of ponatinib in patients with resistant and intolerant CP-CML. However, a high incidence of arterial occlusive events (AOEs) was reported in the study, thought to be dose dependent, which ultimately compromised the utility of the drug, said Shammo.

[OPTIC] asked what dose is needed to be sure that the patients disease is under control and that perhaps we had mitigated the AOEs, said Shammo.

Notably, more than half of patients across dose cohorts had received at least 3 prior TKIs, and approximately a quarter of patients had a T315I mutation, said Shammo.

At a median follow-up of 32 months, the percentage of patients with 1% or less BCR-ABL1 at 12 months was 44.1% (95% CI, 31.7%-57.0%), 29.0% (95% CI, 18.4%-41.6%), and 23.1% (95% CI, 13.4%-35.3%) in the 45-mg, 30-mg, and 15-mg cohorts, respectively.

In the 30-mg and 15-mg cohorts, patients with less-resistant disease and without a T315I mutation at baseline had greater benefit than those with [a] T315I [mutation], said Shammo.

The 3-year OS probabilities were very reasonable, said Shammo, at 89.29%, 88.58%, and 91.71%, respectively. Notably, robust survival outcomes were reported in patients with and without BCR-ABL1 mutations, said Shammo.

What was interesting is that if you had the T315I mutation at baseline, you do need the 45-mg dose, because the response rates [with that dose] seem to be so much better than [those] patients who received a lower dose of ponatinib, said Shammo.

In terms of safety, any-grade treatment-emergent AOEs occurred in 9.6% of patients in the 45-mg arm, 5.3% in the 30-mg arm, and 3.2% in the 15-mg arm; grade 3 or greater rates occurred in 5.3%, 5.3%, and 3.2% of patients, respectively.

At this primary analysis, novel response-based ponatinib dosing regimens had clinically manageable safety and AOE profiles, with an optimal benefit-risk profile achieved with a 45-mg starting dose reduced to 15 mg upon response, concluded Shammo.

Original post:
IDH1 Inhibitors, CAR T-Cell Therapy, and Third-Generation TKIs Refresh Relapsed/Refractory Leukemia Landscape - OncLive