Category Archives: Texas Stem Cells

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 ClinicalTrials.gov.

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 http://www.daiichisankyo.com.

References

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...

Houston, Texas and Tuebingen, Germany, November 1, 2021 Immatics N.V. (NASDAQ: IMTX, Immatics), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, today announced that the company will provide an update on its ACTengine IMA203 trial in a late-breaking oral presentation as well as an update on Immatics next-generation CD8ab TCR-T approach at the 36th Annual Meeting of the Society for Immunotherapy of Cancers (SITC). The conference will take place, both in person and virtually, from November 10 - 14, 2021.

Today, SITC announced presentation titles and timings as follows:

IMA203 Phase 1a Clinical Data Update:

Presentation Title: Safety and anti-tumor activity of TCR-engineered autologous, PRAME-directed T cells across multiple advanced solid cancers at low doses clinical update on the ACTengine IMA203 trialSpeaker: Martin Wermke, MD, Coordinating Investigator of Immatics ACTengine trials in Germany and Head of the Early Clinical Trial Unit of the National Center for Tumor Diseases Dresden (NCT/UCC) at the University Hospital Carl Gustav Carus in Dresden, GermanyAbstract Number: 959 Category: Late-breaking oral abstract presentationDate & Time: Saturday, November 13, 2021; 12:00 - 12:15 pm EDT

Next-generation CD8ab TCR-T approach - Preclinical Data Update:

Presentation Title: Improved anti-tumor activity of next-generation TCR-engineered T cells through CD8 co-expressionSpeaker: Mamta Kalra, PhD, Director CMC (Process Development) at ImmaticsAbstract Number: 163 Category: Poster abstract presentationDate & Time: Friday, November 12, 2021; Poster Hall Hours: 7 am8:30 pm EDT

All posters presented at the poster hall will be made available as virtual ePosters throughout the SITC 36th Annual Meeting.

- END -

About ACTengine IMA200 programsEach of the product candidates of the IMA200 programs is based on Immatics proprietary ACTengine approach in which the patients own T cells are genetically engineered to express a novel, proprietary TCR directed against a defined cancer target. The modified T cells are then reinfused into the patient to attack the tumor, an approach also known as TCR-T. ACTengine programs IMA201, IMA202 and IMA203 are currently in clinical development for the treatment of solid tumor indications, both in the US and in Germany. IMA204 is currently in pre-clinical development. All ACTengine product candidates can be rapidly manufactured utilizing a proprietary manufacturing process designed to enhance T cell engraftment and persistence in vivo.

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The ACTengine T cell products are manufactured at the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory in collaboration with UTHealth. The ACTengine IMA200 Programs are co-funded by the Cancer Prevention and Research Institute of Texas (CPRIT).

About ImmaticsImmatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer.

For regular updates about Immatics, visit http://www.immatics.com. You can also follow us on Twitter and LinkedIn.

For more information, please contact:

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Immatics to Present Update on Lead ACTengine Program IMA203 Targeting PRAME at the Society for Immunotherapy of Cancers 36th Annual Meeting - Yahoo...

A poster presentation featuring preclinical data on AFM28, a novel Innate Cell Engager developed for treatment of Acute Myeloid Leukemia and other CD123+ myeloid malignanciesA poster presentation on AFM13 precomplexed NK cells that maintained biological activity and potency after one cycle of freezing, resulting in a cryopreserved, off-the-shelf CAR-like NK cell therapyA company sponsored investor event in mid-December to provide a clinical development update on AFM13

HEIDELBERG, Germany, Nov. 04, 2021 (GLOBE NEWSWIRE) -- Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, today announced that it will present two posters on its innate cell engagers (ICE) at the 63rd American Society of Hematology Annual Meeting and Exposition (ASH).

Details of presentations:

Poster presentation 1:

Title: AFM28, a Novel Bispecific Innate Cell Engager (ICE), Designed to Selectively Re-Direct NK Cell Lysis to CD123+ Leukemic Cells in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Abstract: 3344

Authors: Gtz J-J., Pahl J., Schmitt N., Mller T., Haneke T., Kozlowska I., Sarlang S., Knackmuss S., Peters E., Reusch U., Ross T., Nowak D., Hofmann W-K. and Merz C.

Presentation time: Monday December 13, 2021, 6:00 PM - 8:00 PM EST

AFM28 is a novel ICE, developed on Affimeds ROCK platform, specifically designed to address patient needs in Acute Myeloid Leukemia (AML) and other CD123+ myeloid malignancies, including high-risk Myelodysplastic Syndrome (MDS).

The bispecific, tetravalent antibody AFM28 binds selectively and with high affinity the surface antigen CD123, which is almost universally expressed on leukemic blast and leukemic stem cells in AML, and CD16A on NK cells. It is thereby initiating antibody-dependent cell-mediated cytotoxicity (ADCC) against CD123+ tumor cells and is well suited to be investigated as monotherapy and in combination with allogeneic NK cell transfer. AFM28 is currently in preclinical development and a first-in-human clinical study is expected to start in the second half of 2022.

Poster presentation 2:

Title: Cryopreserved CAR-like NK Cells Pre-Complexed with the CD30/CD16A Bispecific Innate Cell Engager (ICE) AFM13 for the Treatment of CD30+ Malignancies

Abstract: 3992

Authors: Reusch U., Ellwanger K., Fucek I., Mller T., Schniegler-Mattox U., Pahl J., Tesar M., and Koch J.

Presentation time: Monday, December 13, 2021, 6:00 PM - 8:00 PM EST

AFM13 precomplexed NK cells maintained biological activity and potency after one cycle of freezing, demonstrating a promising approach to develop a cryopreserved off-the-shelf CAR-like NK cell immunotherapeutic. The high ADCC potency and efficacy of NK cells were maintained and a long cell surface retention, independent of CD16A polymorphism, has been demonstrated. The data to be presented support the development of a cryopreserved, off-the shelf ICE / NK cell product, adding to the clinical utility of the treatment.

Full abstracts of the presentations are published in the November supplemental issue of Blood, a publication of the American Society of Hematology. Classical posters, as well as short poster presentations, including a slide deck and graphic poster will be available for in-person and virtual attendees.

For more details about the ASH Virtual Annual Meeting please visit: https://www.hematology.org/meetings/annual-meeting.

Company sponsored event on AFM13 in mid-December

Affimed intends to host an investor event to provide a clinical development update on AFM13.AFM13 is currently investigated in two clinical studies: (i) in AFM13-202, as monotherapy in peripheral T cell lymphoma (PTCL); and (ii) in AFM13-104, in combination with adoptive NK cell transfer in CD30-positive lymphomas. Affimed will provide further guidance about the event in early December.

The clinical study AFM13-104, currently underway at The University of Texas MD Anderson Cancer Center, is evaluating AFM13 precomplexed with cord blood-derived NK cells in patients with CD30-positive lymphoma. In April 2021, initial data from the dose escalation portion of the study showed an objective response rate of 100% (2 complete responses and 2 partial responses) in four patients with relapsed/refractory Hodgkin Lymphoma. The dose-escalation part (3 dose levels, each 3 patients) was completed in July 2021 and additional patients have since been enrolled at the highest dose level.

About AFM28

AFM28, a tetravalent, bispecific CD123- and CD16A-binding ICE developed on Affimeds ROCK platform, is designed to bring a new immunotherapeutic approach to patients with CD123+ myeloid malignancies, including acute myeloid leukemia and myelodysplastic syndrome (MDS). It engages NK cells to initiate tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC), even at low CD123 expression levels. Clinical development is planned as both monotherapy and in combination with allogeneic NK cells in patients with relapsed/refractory CD123+ myeloid disease.

About AFM13

AFM13 is a first-in-class ICE that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating NK cells and macrophages. AFM13 is Affimeds most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides (REDIRECT). The study is actively recruiting, and additional details can be found at http://www.clinicaltrials.gov (NCT04101331).

In addition, The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored phase 1 trial in combination with cord blood-derived allogeneic NK cells in patients with relapsed/refractory CD30-positive lymphomas (NCT04074746).

About Affimed N.V.

Affimed (Nasdaq: AFMD) is a clinical-stage immuno-oncology company committed to give patients back their innate ability to fight cancer by actualizing the untapped potential of the innate immune system. The companys proprietary ROCK platform enables a tumor-targeted approach to recognize and kill a range of hematologic and solid tumors, enabling a broad pipeline of wholly-owned and partnered single agent and combination therapy programs. The ROCK platform predictably generates customized innate cell engager (ICE) molecules, which use patients immune cells to destroy tumor cells. This innovative approach enabled Affimed to become the first company with a clinical-stage ICE. Headquartered in Heidelberg, Germany, with offices in New York, NY, Affimed is led by an experienced team of biotechnology and pharmaceutical leaders united by a bold vision to stop cancer from ever derailing patients lives. For more about the companys people, pipeline and partners, please visit: http://www.affimed.com.

Forward-Looking Statements

This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as anticipate, believe, could, estimate, expect, goal, intend, look forward to, may, plan, potential, predict, project, should, will, would and similar expressions. Forward-looking statements appear in a number of places throughout this release and include statements regarding our intentions, beliefs, projections, outlook, analyses and current expectations concerning, among other things, the potential of AFM13, AFM24, AFM28 and our other product candidates, the value of our ROCK platform, our ongoing and planned preclinical development and clinical trials, our collaborations and development of our products in combination with other therapies, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates, our intellectual property position, our collaboration activities, our ability to develop commercial functions, clinical trial data, our results of operations, cash needs, financial condition, liquidity, prospects, future transactions, growth and strategies, the industry in which we operate, the trends that may affect the industry or us, impacts of the COVID-19 pandemic, the benefits to Affimed of orphan drug designation and the risks, uncertainties and other factors described under the heading Risk Factors in Affimeds filings with the SEC. Given these risks, uncertainties, and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future.

Investor Relations Contact

Alexander Fudukidis Director, Investor Relations E-Mail: a.fudukidis@affimed.com Tel.: +1 (917) 436-8102

Media Contact

Mary Beth Sandin Vice President, Marketing and Communications E-Mail: m.sandin@affimed.com Tel.: +1 (484) 888-8195

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Several presentations will highlight broad potential of CD19-targeted ADC ZYNLONTA (loncastuximab tesirine-lpyl) as a single agent and in combination for the treatment of non-Hodgkin lymphomas

LAUSANNE, Switzerland--(BUSINESS WIRE)--ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs) for patients with hematologic malignancies and solid tumors, today announced abstracts for ZYNLONTA and ADCT-602 have been accepted for presentations at the 63rd American Society of Hematology (ASH) Annual Meeting, which will be held virtually and in Atlanta, Georgia from December 11-14, 2021.

We look forward to sharing data on our targeted ADCs as single agents and in innovative combinations at the 2021 ASH Annual Meeting, said Joseph Camardo, MD, Chief Medical Officer of ADC Therapeutics. This will include presentations from investigators on subset data from our pivotal Phase 2 study and data on the use of ZYNLONTA post-CAR-T. We are also encouraged by the anti-tumor activity and manageable safety profile of ZYNLONTA in combination with ibrutinib. The Phase 2 protocol has recently been amended with a higher and more frequent dose of ZYNLONTA to potentially enhance the response and to investigate this combination in earlier lines of therapy.

Details of ADC Therapeutics oral presentation are as follows:

Planned Interim Analysis of a Phase 2 Study of Loncastuximab Tesirine Plus Ibrutinib in Patients with Advanced Diffuse Large B-Cell Lymphoma (LOTIS-3)Abstract: 54Date and Time: Saturday, December 11, 2021, 10:45 a.m. ESTSession: 627. Aggressive Lymphomas: Clinical and Epidemiological: Population data for Aggressive NHL ManagementPresenter: Carmelo Carlo-Stella, MD, Department of Biomedical Sciences, Humanitas University, and Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy

Details of ADC Therapeutics poster presentations are as follows*:

Clinical Characteristics and Responses of Patients with Relapsed or Refractory High-Grade B-cell Lymphoma Treated with Loncastuximab Tesirine in the LOTIS-2 Clinical TrialAbstract: 3575Date: Monday, December 13, 2021Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster IIIPresenter: Juan Pablo Alderuccio, MD, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

Combination of Loncastuximab Tesirine and Polatuzumab Vedotin Shows Increased Anti-Tumor Activity in Pre-Clinical Models of Non-Hodgkin LymphomaAbstract: 2273Date: Sunday, December 12, 2021Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster IIPresenter: Francesca Zammarchi, PhD, ADC Therapeutics

CD19-mediated DNA Damage Boost in Lymphoma Cells Treated with Loncastuximab Tesirine in Combination with PARP inhibitorsAbstract: 1342Date: Saturday, December 11, 2021Session: 622. Lymphomas: TranslationalNon-Genetic: Poster IPresenter: Stefania Fusani, PhD, Oncohematology Division, IEO Istituto Europeo di Oncologia IRCCS, Milano, Italy

Details of an independently developed ZYNLONTA poster are as follows:

The Anti-CD19 Antibody-Drug Conjugate Loncastuximab Tesirine Achieved Responses in Patients with Diffuse Large B-cell Lymphoma Who Relapsed After Anti-CD19 CAR T-Cell TherapyAbstract: 2489Date: Sunday, December 12, 2021Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster IIPresenter: Paolo F. Caimi, MD, Cleveland Clinic/Case Comprehensive Cancer Center, Cleveland, OH, USA

Details of an independently developed ADCT-602 poster are as follows:

A Phase 1 Trial of ADCT-602, a CD22 Targeting Antibody Drug Conjugate Bound to PBD Toxin in Adult Patients with Relapsed or Refractory CD22+ B-Cell Acute Lymphoblastic LeukemiaAbstract: 1237Date: Saturday, December 11, 2021Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster IPresenter: Nitin Jain, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

*Posters will be available in the poster exhibit hall in the Georgia World Congress Center on these dates: December 11: 9:00 a.m.7:30 p.m. EST; December 12 & 13: 9:00 a.m.8:00 p.m. EST. Presenters planning to attend in-person are expected to present during the final two hours of the noted viewing time.

The abstracts are available through the ASH online meeting program and will be published in the November supplemental issue of Blood.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

About ADC Therapeutics

ADC Therapeutics (NYSE: ADCT) is a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs). The Company is advancing its proprietary PBD-based ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors.

ADC Therapeutics CD19-directed ADC ZYNLONTA (loncastuximab tesirine-lpyl) is approved by the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents. Cami (camidanlumab tesirine) is being evaluated in a late-stage clinical trial for relapsed or refractory Hodgkin lymphoma and in a Phase 1b clinical trial for various advanced solid tumors. In addition to ZYNLONTA and Cami, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development.

ADC Therapeutics is based in Lausanne (Biople), Switzerland and has operations in London, the San Francisco Bay Area and New Jersey. For more information, please visit https://adctherapeutics.com/ and follow the Company on Twitter and LinkedIn.

ZYNLONTA is a registered trademark of ADC Therapeutics SA.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211104005798/en/

InvestorsEugenia LitzADC TherapeuticsEugenia.Litz@adctherapeutics.comTel.: +44 7879 627205

Amanda HamiltonADC Therapeuticsamanda.hamilton@adctherapeutics.comTel.: +1 917 288 7023

EU MediaAlexandre MllerDynamics Groupamu@dynamicsgroup.chTel: +41 (0) 43 268 3231

USA MediaMary Ann OndishADC Therapeuticsmaryann.ondish@adctherapeutics.comTel.: +1 914-552-4625

Source: ADC Therapeutics SA

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ADC Therapeutics Announces Abstracts to be Presented at the 63rd ASH Annual Meeting - StreetInsider.com

Using BK virus (BKV)-specific T cells from healthy donors to treat BKV-associated hemorrhagic cystitis, a painful side effect associated with immunosuppression from stem cell transplants, may relieve the complication faster in patients with lymphoma or leukemia, according to trial results.

What was very important was that within a week of giving the cells, the majority of patients symptoms improved, Dr. Katy Rezvani, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center in Houston and lead study author, said in an interview with CURE. The effect of the cells is relatively rapid.

BKV-associated hemorrhagic cystitis occurs more frequently in patients with leukemia or lymphoma who received a treatment of allogeneic stem cell transplantation. As a result, it can lead to patients having blood in their urine and passing clots, which can cause urinary retention (difficulty urinating or completely emptying the bladder) and, in more severe cases, kidney disease.

In patients who receive stem cell transplants, those who have a half match (when patients only have some genetic similarities with the donors immune system) are at an increased risk for BKV-associated hemorrhagic cystitis because they are more immunosuppressed. Approximately 40% of patients who have a half match develop this complication.

In the phase 2 trial, BKV-specific T cells, which recognize and attack BKV, from healthy donors were given once intravenously, with the option to receive additional doses every two weeks if needed. Of the 59 patients enrolled in the trial, 67.7% had complete (all symptoms resolved) or partial (almost all symptoms resolved) responses within 14 days. This increased to 81.6% after 28 days.

Some intolerance was observed in patients who were previously treated with steroids, which can kill T cells. There were no side effects, and there were no reports of new liver or gastrointestinal graft-versus-host disease (GVHD, occurs when the donor's cells attack the patient's cells) associated with the antiviral T cells, aside from a few cases of skin GVHD that quickly resolved with corticosteroids.

This treatment has the potential to stop the vicious cycle that comes with the current standard of care, which consists of hospitalization with continuous bladder irrigation (using a catheter to wash out the bladder) and morphine infusion to help patients tolerate the pain, according to Rezvani.

This outpatient treatment is preventing patients from having to be admitted (to the hospital), which is wonderful because patients come into hospital with one thing, they stay in the hospital for a few weeks, then they develop other complications, Rezvani explained. They start getting other infections, they get pneumonia, they become malnourished, etc.

According to Rezvani, one donor can produce up to 50 doses of T cells, which are frozen until needed. Every time the patient comes (into the hospital), within 24 hours we can treat them, she said.

Of note, the therapy is only available at MD Anderson, so patients with the complication would need to travel to the health center to receive it an option that may not be possible because of physical condition or finances. Im hoping that we will get to a situation where well be able to start a multicenter study at some point, Rezvani said, which would make the care more accessible to patients. In the meantime, I think the greatest limitation really is that patients will have to come to MD Anderson to receive the treatment, and for many patients with the terrible BKV hemorrhagic cystitis, this is not obviously possible.

Until then, Rezvani is focusing on the next generation of the treatment: genetically modifying BKV-specific T cells that are more resistant to steroids, thus broadening the patient spectrum that the treatment could help.

Its important to realize that the use of immunotherapy against viruses and cancers (has) opened up a very exciting new era of treatment for our patients, she concluded. We are learning a lot more from the immune system (and are harnessing) the power of the immune system to fight infections and cancers. ... I think the field is going to continue to grow, and many more such treatments to target both viruses and cancers (are) going to become available.

For more news on cancer updates, research and education, dont forget tosubscribe to CUREs newsletters here.

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The Power of the Immune System: New Treatment for Painful Blood Cancer Side Effect - Curetoday.com

RESEARCH TRIANGLE PARK Durham-basedAltis Biosystemsis offering a research award of up to $10,000 for a scientific team to use its proprietary drug-development technology in a research project.

Altis is soliciting proposals from company and academic scientists to use RepliGut, its patented platform that replicates the intestinal epithelium, the thin layer of cells that line the small and large intestines and are vital to good health.

Altis has always been at the forefront of innovative and more-biologically relevant research to enable the development of more effective drugs, said Michael Biron, the companys chief executive officer. We view this research award as a way to further this development with partners to produce meaningful and informative scientific experiments to advance their pipelines.

.The use of RepliGut will also help Altis gather feedback on the technology to help broaden its applications, said Niki Heinz, director of business development at Altis.

We have this really unique technology, Heinz said. As many brains as we can have working on this in terms of what people want to do with it, the better.

Interested researchers working in drug discovery, safety, immunology, and inflammation can propose a project with RepliGut by completinga form on the companys websiteby Nov. 15.A project will be chosen by Dec. 10, and work will get under way by Jan. 15, 2022.

Potential applicants can gather more information about RepliGut by viewing an Oct. 12webinarfeaturing Bill Thelin, Ph.D., chief scientific officer at Altis. Thelin will address how intestine-on-a-chip technology can reliably model gastrointestinal disease and help researchers screen for safe, effective therapeutic candidates.

.RepliGut recreates the human intestinal epithelium in a high-throughput format for more biologically relevant screening of compounds, disease modeling and microbiome research.

Altis sells RepliGut as a kit and also provides a variety of contract research services for customers involving inflammation, barrier function, toxicology and drug disposition.

Intestinal stem cells used for the RepliGutsystem are harvested from transplant-grade human donor tissue for which there is no recipient match. Compounds and other cell types interact with the epithelial cells in a multi-well plate format that allows for high-throughput screening and integration with standard laboratory equipment and workflows.

With this design, RepliGutcan model different behaviors in the intestine, such as the barrier function, more accurately than typical methods that use cancer cell lines or animal models.

The companys goal for RepliGut is to reduce the time and cost of drug development with a platform that more closely represents native human biology and to reduce the need for animal testing.

RepliGuts core use is for screening drug compounds, but its utility is expanding to include gene expression and other downstream assays, Heinz said. Altis this summer hired Thelin as chief scientific officer to help broaden the platforms capacity.

The RepliGut technology was developed in the Biomedical Engineering Department at the University of North Carolina at Chapel Hill, and Altis was formed in 2017 to commercialize it.

Last August Altis raised $3.1 million in a seed series investment that was oversubscribed by nearly 50 percent. The round was led by VentureSouth of Greenville, S.C., and also involved local investors including RTP Capital and Hatteras Ventures, as well as other syndicate partners across the country including Atlanta Technology Angels and Central Texas Angel Network.

Altis declined to disclose its employment total but is adding staff to further develop RepliGut.

We have been hiring for the last month or so and continue to look for talent, Heinz said.

The company recently hiredseveral scientists to keep up with customer projectsand now is looking for a senior director of operations. It will be seekingadditionalscientists in the next couple of months, she said, as the company looks to expand its offerings to the research community.

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Durham firm offering up to $10,000 for researchers to use its intestinal technology - WRAL Tech Wire

Although visible signs of aging are usually unmistakable, unraveling what triggers them has been quite a challenge. At Baylor College of Medicine, the lab of Dr. Weiwei Dang and others at collaborating institutions have discovered that a cellular phenomenon called cryptic transcription, which had been previously described and linked to aging in yeasts and worms, is elevated in aging mammalian stem cells.

In previous work, we showed that cryptic transcription in yeasts and worms is not only a marker of aging but also a cause, said corresponding author Dang, assistant professor ofmolecular and human geneticsand theHuffington Center on Agingat Baylor. Reducing the amount of this aberrant transcription in these organisms prolonged their lifespan.

Cryptic transcription is a phenomenon that interferes with normal cellular processes. Normal gene transcription is a first step in the production of proteins. It begins in a specific location on the DNA called the promoter. This is where the protein coding gene begins to be transcribed into RNA, which is eventually translated into protein.

Gene transcription is a well-regulated cellular process, but as cells age, they lose their ability to control it.

Promoters have a specific DNA sequence that identifies the starting point of the transcription process that is usually located preceding the actual protein coding sequence, explained Dang. But promoter look-alike sequences do exist in other locations, including along the actual protein coding sequence, and they could start transcription and generate shorter transcripts, called cryptic transcripts. Here we investigated whether cryptic transcription increased with age in mammals and potential mechanisms involved in this phenomenon.

The team worked with mammalian stem cells, which have shown to play a significant role in aging. They adapted a method to detect cryptic transcription to determine the level of this transcription in mice and human stem cells and cultured cells. When compared to young stem cells, older ones had increased cryptic transcription. They also looked into other aging cells and found that, in the majority of cells spanning a range of tissues, cryptic transcription was also elevated with age.

Altogether, our findings indicate that elevated cryptic transcription is emerging as a hallmark of mammalian aging, Dang said.

Young cells have mechanisms in place to prevent cryptic transcription. In aged mammalian cells, the researchers found that one such mechanisms, which involves limiting the access to chromatin, the material that makes up the chromosomes, is failing, facilitating the production of cryptic transcripts.

It is still not clear how elevated cryptic transcription contributes to aging, but the evidence is accumulating that it is detrimental to mammals as it is for yeast and worms, Dang said. Future studies may result in ways of reduce the pro-aging effects of cryptic transcription.

Read the complete report in the journalNature Aging.

Other contributors to this work include Brenna S. McCauley, Luyang Sun, Ruofan Yu, Minjung Lee, Haiying Liu, Dena S. Leeman, Yun Huang and Ashley E. Webb. The authors are associated with one or more of the following institutions: Baylor College of Medicine, Texas A&M University, University of Texas MD Anderson Cancer Center, Stanford University, Genentech and Brown University.

This work was funded by NIH grants R01AG052507, R01AG053268, R01HL134780, R01HL146852 and T32AG000183; CPRIT award R1306 and a Ted Nash Long Life Foundation research grant.

By Ana Mara Rodrguez, Ph.D.

Read more from the original source:
Elevated cryptic transcription emerges as a common theme in aging mammalian cells - Baylor College of Medicine News

Although visible signs of aging are usually unmistakable, unraveling what triggers them has been quite a challenge. Researchers at Baylor College of Medicine and collaborating institutions have discovered that a cellular phenomenon called cryptic transcription, which had been previously described and linked to aging in yeasts and worms, is elevated in aging mammalian stem cells.

The team reports in the journal Nature Aging that cryptic transcription occurs because a cellular mechanism that keeps it in check falls apart as cells get old. The findings suggest that strategies that control cryptic transcription could have pro-longevity effects.

In previous work, we showed that cryptic transcription in yeasts and worms is not only a marker of aging but also a cause, said corresponding author Dr. Weiwei Dang, assistant professor of molecular and human genetics and the Huffington Center on Aging at Baylor. Reducing the amount of this aberrant transcription in these organisms prolonged their lifespan.

Cryptic transcription is a phenomenon that interferes with normal cellular processes. Normal gene transcription is a first step in the production of proteins. It begins in a specific location on the DNA called the promoter. This is where the protein coding gene begins to be transcribed into RNA, which is eventually translated into protein. Gene transcription is a well-regulated cellular process, but as cells age, they lose their ability to control it.

Promoters have a specific DNA sequence that identifies the starting point of the transcription process that is usually located preceding the actual protein coding sequence, explained Dang. But promoter look-alike sequences do exist in other locations, including along the actual protein coding sequence, and they could start transcription and generate shorter transcripts, called cryptic transcripts. Here we investigated whether cryptic transcription increased with age in mammals and potential mechanisms involved in this phenomenon.

The team worked with mammalian stem cells, which have shown to play a significant role in aging. They adapted a method to detect cryptic transcription to determine the level of this transcription in mice and human stem cells and cultured cells. When compared to young stem cells, older ones had increased cryptic transcription. They also looked into other aging cells and found that, in the majority of cells spanning a range of tissues, cryptic transcription was also elevated with age.

Altogether, our findings indicate that elevated cryptic transcription is a hallmark of mammalian aging, Dang said.

Young cells have mechanisms in place to prevent cryptic transcription. In aged mammalian cells, the researchers found that one such mechanisms, which involves limiting the access to chromatin, the material that makes up the chromosomes, is failing, facilitating the production of cryptic transcripts.

It is still not clear how elevated cryptic transcription contributes to aging, but the evidence is accumulating that it is detrimental to mammals as it is for yeast and worms, Dang said. Future studies may result in ways of reduce the pro-aging effects of cryptic transcription.

Other contributors to this work include Brenna S. McCauley, Luyang Sun, Ruofan Yu, Minjung Lee, Haiying Liu, Dena S. Leeman, Yun Huang and Ashley E. Webb. The authors are associated with one or more of the following institutions: Baylor College of Medicine, Texas A&M University, University of Texas MD Anderson Cancer Center, Stanford University, Genentech and Brown University.

Reference:McCauley BS, Sun L, Yu R, et al. Altered chromatin states drive cryptic transcription in aging mammalian stem cells. Nat Aging. 2021. doi: 10.1038/s43587-021-00091-xThis article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Cryptic Transcription in Mammalian Stem Cells Linked to Aging - Technology Networks

Bioengineers from Rice University, in Houston, Texas, will use insulin-producing beta cells made from human stem cells to create an implant that senses and regulates blood glucose levels by responding with the correct amount of insulin at a given time.

The three-year research project is between the laboratories of Omid Veiseh and Jordan Miller and supported by a grant from JDRF, a leading global funder of diabetes research. Veiseh, an assistant professor of bioengineering, has over a decade of experience developing biomaterials that protect implanted cell therapies from the immune system. Miller, an associate professor of bioengineering, has spent over 15 years researching techniques to 3D print tissues with vasculature, or networks of blood vessels.

Type 1 diabetes is an autoimmune condition that causes the level of glucose in the blood to fall or rise to dangerous levels. This happens because the condition prevents the pancreas from producing enough insulin to properly regulate blood glucose. Currently, controlling blood glucose as a Type 1 diabetic requires daily insulin injections or wearing an insulin pump.

Veiseh said: If we really want to recapitulate what the pancreas normally does, we need vasculature.

And thats the purpose of this grant with JDRF. The pancreas naturally has all these blood vessels, and cells are organised in particular ways in the pancreas. Jordan and I want to print in the same orientation that exists in nature.

To test the implants first, the researchers will survey their efficacy in regulating the blood glucose levels of mice for at least six months. To do this, they will need to ensure their engineered beta cells can respond to rapid changes in blood sugar levels.

We must get implanted cells in close proximity to the bloodstream so beta cells can sense and respond quickly to changes in blood glucose, Miller said.

Miller added that insulin-producing cells should be no more than 100 microns from a blood vessel.

Were using a combination of pre-vascularisation through advanced 3D bioprinting and host-mediated vascular remodelling to give each implant several shots at host integration, Miller said.

The insulin-producing cells will be protected with a hydrogel formulation developed by Veiseh, who is also a Cancer Prevention and Research Institute of Texas Scholar. The hydrogel material, which has proven effective for encapsulating cell treatments in bead-sized spheres, has pores small enough to keep the cells inside from being attacked by the immune system but large enough to allow for the passage of nutrients and insulin.

The researchers noted that, if the implant is too slow to respond to high or low blood sugar levels, the delay can produce a roller-coaster-like effect, where insulin levels repeatedly rise and fall to dangerous levels.

Addressing that delay is a huge problem in this field, Veiseh said. When you give the mouse and ultimately a human a glucose challenge that mimics eating a meal, how long does it take that information to reach our cells, and how quickly does the insulin come out?

By incorporating blood vessels in their implant, Veiseh and Miller hope to enable the beta-cell tissues to behave in a way that more closely mimics the natural behaviour of the pancreas.

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Insulin-producing implants are being developed to control Type 1 diabetes - Health Europa

LorettaNastoupil, MD: Hello, and thank you for joining this Targeted Oncology presentation, entitled, CD19 asaTherapeutic TargetinDiffuse Large B-Cell Lymphoma [DLBCL]. Patients with relapsed/refractory [R/R] diffuse large B-cell lymphoma DLBCL who are ineligible for autologous stem cell transplant have relatively few treatment options and poor outcomes. CD19 [cluster of differentiation 19] has become a therapeutic target of increasing interest, and both CAR [chimeric antigen receptor] T-cell therapy and [use of] monoclonal antibodies directed at CD19 have shown promise in this patient population. In today's Precision Medicine and Oncology discussion, we will talk about the role of CD19 in the therapeutic landscape for patients with transplant-ineligible, R/R DLBCL. I'm Dr LorettaNastoupil, associate professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston. Joining me today is my colleague, Dr John Burke, a hematologic oncologist at Rocky Mountain Cancer Center in Aurora, Colorado. Thank you so much for joining.

John, how common is DLBCL?

John Burke, MD:Hi, Loretta. DLBCL is the most common subtype of non-Hodgkin's lymphoma [NHL]. There are about 80,000 or so cases of NHL diagnosed each year in the US, and about one-third of these are DLBCL. It puts it around 25,000 cases per year in the US. The incidence is in the ballpark of 6 new cases per 100,000 per year, and it's slightly more common in men than in women. It's the most common of the NHLs, so I think most community oncologistsdefinitely seea fair amount.

LorettaNastoupil, MD:We spent the last probably 10-plus years talking about germinal center versus non-germinal center subtypes. How does this distinction impact prognosis, and do you use it for treatment selection?

John Burke, MD:Yes. We've known for more than 20 years that one can divide DLBCL into a couple of different groups based on the expression of genes within cancer cells. This can be done via a technique called gene-expression profiling. When you apply gene-expression profiling to large cell lymphoma, you can classify it as either a germinal-center B subtype or an activated B-cell subtype. Gene-expression profiling is a technique that's not widely used in practice. Several years after [this advance], it was discovered that using immunohistochemical staining canserve as an estimate of the gene expression profilerelated classification of these lymphomas.

What's usually done in clinical practice now is that pathologists will use immunohistochemical staining and algorithms to describe DLBCL as germinal center B or non-germinal center B subtypes. Then the question is, Does this impact your treatment? The answeris thata lot of attempts have been made in the last couple of decades to target therapies toward different subtypes of DLBCL, and really none of those has stuck or proven to be truly beneficial. At this point, at least in my practiceand I'm curious to hear about yoursit really hasn't affected treatment. As for prognosis, we do know that the activated B-cell subtype generally has a less favorable prognosis than [does] the germinal center B subtype when conventional treatments are used. How about you? Isthis something that affects your practice at all day-to-day?

LorettaNastoupil, MD:No, not really. And, as you mentioned, its not likely, because there has beena number ofrandomized studies that have failed to demonstrate an improvement over R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine sulfate (Oncovin), prednisone]. Well, it probably had the biggest impact, as we've just had more trials, generally speaking, forthe nongerminal center subtype. Moving forward, our trials have become agnostic to this.

Transcript edited for clarity.

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Overview of DLBCL - Targeted Oncology