Category Archives: Cell Therapy

Just a few months after GlaxoSmithKline penned a $50 million deal with biotech Immatics for its T-cell work, the executive running the Big Pharmas cancer cell therapy unit is upping sticks to join the U.S.-European startup.

Cedrik Britten, M.D., becomes the biotechs new chief medical officer to help run its adoptive cell therapy and T-cell receptor (TCR) bispecifics platform, which is focused on various solid tumors.

This platform has seen it pen a series of collaborations in recent years, leveraging its pool of around 200 targets to land deals with Amgen, Celgene and Genmab.

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One of the more recent partners has been GSK, Brittens former employer, where he had been vice president and head of the oncology cell therapy research unit for five years, joining the U.K. Big Pharma after serving at Germanys BioNTech.

Back in February, GSK struck a deal to access two of Immatics' TCR therapeutics, seeing it nab $50 million (46 million) upfront with $550 million in milestones for TCRs against two solid tumor targets identified by Immatics.

At the time, Immatics CEO Harpreet Singh told FierceBiotech that the way he sees it, the deals are testament to the potential for TCR therapies to expand the list of solid tumors that are amenable to treatment using immunotherapies.

The target space that we can tap into with our platforms and technologies is approximately three to four times bigger than the CAR-T space. What we can do with TCRs is tap into intracellular targets, which are not accessible to CAR-Ts and antibodies, Singh said.

Now, he has GSKs leading cell therapy exec to help push on in this space.

This change-up has caused some shuffles in the company and one exit. Carsten Reinhardt, M.D., Ph.D., the current CMO, will take on the newly created role of chief development officer to lead Immatics product development strategy.

Carsten will also continue to lead the TCR bispecifics platform and pipeline as well as the immunology and translational development functions at Immatics.

But this means there is no room for ex-Astellas exec Stephen Eck, M.D., Ph.D., who had been its CMO in Houston and will exit the biotech at the end of June but stay on for a few weeks to to support the transition. Eck left Fiercer 15 winner Aravive Biologics as its CEO in 2018 to take up the CMO role at Immatics.

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GSK's cell therapy R&D lead jumps ship to partner Immatics - FierceBiotech

Optimized tandem CD19/CD20 chimeric antigen receptor (CAR) T-cell therapy induced potent and durable anti-tumor responses as treatment of patients with relapsed/refractory B cell non-Hodgkin lymphoma (B-NHL) with good control of cytokine release syndrome (CRS) and CAR T-related encephalopathy syndrome, according to a phase 1/2 clinical trial presented in a poster at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

After a median of 13.5 months of follow-up (IQR, 33.2-3.3), 84% of patients had an objective response, and 74% had a complete response (CR). The duration of overall response rate (ORR) at 6 months was 94% and 74% at 12 months.

Both the median progression-free and overall survivals had not been reached for patients at the time of data cut-off. At 6 months, the progression-free survival rate was 76%, and at 12 months, it was 59%.

Sixty-two patients experienced CRS (71%), which was grade 1 or 2 in 61% of patients and grade 3 or greater in 10%. The median time to the onset of CRS after infusion was 1 day (range, 1-5). The median duration of CRS was 6 days (range, 1-9). Investigators also noted that the median time to the onset of grade 3 CRS was 1 day (range, 1-2).

The most common adverse events within 1 month of the IV infusion were leukopenia, pyrexia, and anorexia. Only 2 patients (2%) experienced CAR T-cell-related encephalopathy syndrome of grade 3 severity.

Three treatment-related deaths occurred in the study, 2 due to pulmonary infection and 1 due to deposition of CAR T cells in pulmonary alveoli.

Ninety-nine patients were screened for the study, of which 87 received the infusion and 74 were followed for at least 3 months before the data cutoff date. Patients underwent leukapheresis and conditioning chemotherapy, which was followed by a single intravenous infusion of tandem CD19/20 CAR T cells on day 0 at a dose of 0.5x106x106 per kg of body weight.

The majority of patients in the study were under the age of 60 years (82%) and female (53%). Overall, 62% of patients had an ECOG performance status of 0 or 1 versus 38% who had a 2. Upon study entry, 85% had stage III or IV disease and 15% had stage I or II. Patients were diagnosed with either diffuse large B-cell lymphoma (66%), follicular lymphoma (15%), transformed follicular lymphoma (7%), primary mediastinal B-cell lymphoma (6%) or other (6%).

Fifty-six percent of patients had 3 to 5 prior lines of anti-neoplastic therapy, while 27% had 2 or less and 17% had 6 or more. The majority of patients had a lesion diameter less than 10 cm (78%) and had tumor burden SPD of 100 cm2 or more (55%). Eighty percent of the patients were refractory, 20% had relapsed to second-line or later therapy, 14% became refractory after stem cell transplant, and 10% had relapsed after a prior CD19 CAR-T cell therapy.

To be eligible for the study, patients had to be between the ages of 16 and 70 years, and they could not have received prior anti-CD20 monoclonal antibody and anthracycline treatment. Patients had to have an ECOG performance status of 0 to 2 with a life expectancy greater than 3 months and adequate organ function to enroll in the study. Patients also had to have measurable disease according to the IWG Response Criteria for Malignant Lymphoma.

Patients who had a CR with no evidence of disease were ineligible to enroll. If they had definite involvement of the gastrointestinal tract, negative tumor puncture detection in both CD19 and CD20, or had serious uncontrolled medical disorders or active infections, they also could not enroll. Patients were also excluded from the study if they were deemed unsuitable for the trial based on clinical judgement or were pregnant or lactating.

CD19-targeted CAR T cells have been highly effective in the treatment landscape of hematologic malignancies, but the recurrence rate appears high, which is a major obstacle to durable remissions with this therapy. This study aimed to evaluate the safety and tolerability of intravenous tandem CD19/20 CAR T cells among patients with relapsed/refractory NHL.

Secondary objectives of this study also included assessment of efficacy of the study treatment defined by ORR and evaluation of the duration of overall response, progression-free and overall survival. An exploratory objective of the study was to determine in vivo expansion and persistence of the Tandem CD19/CD20 CAR T cells.

The rationale for this study was to address the high recurrence rate observed with CAR T-cell therapy, which often prevents durable remission after treatment. Overall the optimized tandem CAR T treatment appeared feasible in patients with B-NHL. Although many of the patients in the study had heavy tumor burden, were in poor physical condition, or had highly aggressive characteristics, they were still able to achieve a satisfactory ORR and CR rate with the tandem CD19/CD20 CAR-engineered T-cell therapy.

Reference

Ja-Jing Z, Yao W, Zhi-Qiang Wu, et al. Safety and Efficacy of Optimized Tandem CD19/CD20 CAR-Engineered T Cells in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma. J Clin Oncol. 38: 2020 (suppl; abstr 3034). doi: 10.1200/JCO.2020.38.15_suppl.3034

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Optimized Tandem CAR T-Cell Therapy Targeted CD19/CD20 Appears Feasible in B-NHL - Targeted Oncology

Cell and gene therapies must scale up on an industrial level if they are to deliver their full potential to patients worldwide, according to speakers at the International Society of Cell Therapy meeting, ISCT Paris 2020 Virtual, May 29.

As the industry moves from clinical to commercial, we are reaching an inflection point and face key challenges, Alberto Santagastino, VP, head of the cell and gene technologies business unit at Lonza, said. Chief among them are improving process development and addressing the manufacturing pressures of technology, timeline, and costs. We need to look at the practicalities of how to make therapies available.

Traditional therapies experience a rapid increase in demand and then plateau. Curative cell and gene therapies, however, will have a steep adoption curve and an almost equally steep decline as the prevalence peak is treated. Afterward, only new incidences remain.

During the life of the therapy, the cost will decline, if history is to be trusted. He cited monoclonal antibodies as an example. Initially, they cost $30,000 per gram. Now they cost hundreds of dollars, or less. Cell and gene therapy developers should assume a similar curve.

When Santagastino talks about the need to industrialize, he really means mass customization rather than the type of industrialization associated with blockbuster drugs. Using a mass customization model, the industry will produce a single, customized product with the same efficacy as a standard, mass-produced product.

Embracing that model means focusing early on platforms.

A major paradigm shift must occur, he told the ISCT audience, to move cell therapy from what can be done at a clinical center to mass customization. For example, manufacturers need to think about moving to 3D bioreactor manufacturing and away from using viral vectors.

Process development is the foundation for successful therapy commercialization, Santagastino continued. He advised thinking very early about how to bring the process to the clinic. This includes determining not only which materials are best for therapeutic development, but also which are readily available in large quantities. Additionally, processes should be designed to they can be completed during one work shift. Allowing a process to extend over multiple work shifts creates difficulties, he said.

Take CAR-T therapies, for example. Autologous therapies differ batch to batch, so standardization is difficult. Developers must deal with the challenges of ensuring T-cell quality, patient health (or death while waiting for the therapy to be developed), commercial viability, scale-up, harvesting and manufacturing failures as well as supply chain issues. At the end of it all, Santagastino said, Wide batch-to-batch variability indicates youre not in control, and that distresses regulators. Lonza is addressing that challenge with an automatic, scalable, single-used system, dubbed Cocoon, for improved process control.

An alternative solution to autologous challenges is to develop allogeneic therapies. They have challenges, too, in the form of multiplex gene editing, scale-up and manufacturing, large-volume downstream processes, purification, quality and GMP tissue sourcing.

For allogeneic therapies, Lonza is addressing the donor variability issue with a pool of what it calls well-characterized super donors. Its also developing a scalable closed bioreactor system to address many but not all of the remaining issues, both upstream and down.

Whichever approach is used to develop cell therapies, Santagastino recommended taking a holistic approach that includes developing an automated quality system, addresses manufacturing variability and considers the entire supply chain.

When Novartis developed Kymriah (tisagenlecleucel), its CAR-T therapy for oncology, it took a comprehensive approach early on. With such a complex and innovative type of therapy, it understood the value of involving multiple stakeholders early on. Therefore, the company worked closely with its scientific partners, regulators, payers and the physicians in clinical trials throughout the development process, Emanuele Ostuni, Ph.D., head of cell & gene therapies Europe at Novartis Oncology, pointed out in a following presentation.

The delivery of autologous therapies is very different from traditional drug development. It creates a host of issues and a need to do things pharma hasnt done before, like providing full customer support, he said at the ISCT meeting.

Dr. Ostuni, therefore, called for a seamless, integrated approach to delivering autologous therapies, similar to the white glove services available for consumer products. This means providing full-circle customer support with live customer service in multiple languages, a secure and user-friendly web portal and a trusted chain of identity as cells are drawn from patients, shipped to manufacturers, reprogrammed and expanded, shipped to caregivers and re-infused into patients.

The global access to this autologous therapy expands the demands, but also adds value to the product. Broad global access helps ensure the value of our therapies is recognized, Dr. Ostuni explained. In launching globally, Novartis remained flexible, working with payers who each have slightly different needs and approaches to ensure the therapy was reimbursed.

From a payers perspective, cell therapy is unlike traditional drugs. Traditionally, payers collect one-year, budgetary data on a drug, but data from cell therapies should be analyzed over multiple years. Thats why some payers balk at therapies that are initially expensive but are cost-effective in the long-term.

That difference creates the need for a lot of innovation to ensure the value of the therapy is recognized and that a sustainable commercial arrangement is developed, Dr. Ostuni said. This isnt how most diseases are managed, and payers arent used to it.

Innovation must happen on multiple fronts, he emphasized. For CAR-T therapy at Novartis, this meant addressing immunogenicity by using humanized constructs, safety by ensuring early anticytokine activity, resistance by targeting the tumor microenvironment and relapse by combining two CAR-T products for better targeting.

Along the way, manufacturing had to be improved to ensure scalability for this allogeneic off-the-shelf product. Scaleup is critical, Dr. Ostuni said. We invested the effort and capital to ensure a broad manufacturing network to supply regions of the world and thus simplify logistics. We have a multi-source environment, so an emergency at one facility wont negatively affect supplies. Two European facilities are coming on line in a few months, and more will be online later.

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Why Cell and Gene Therapies Need a Paradigm Shift to Enable Commercial Scale-up - BioSpace

GC027,the first humanized chimeric antigen receptor (CAR)-T cell therapy for relapsed/refractoryT-cell acute lymphoblastic leukemia (T-ALL) in adults, appears to be botheffective and have a manageable safety profile, according to research presentedduring the ASCO20 Virtual Scientific Program.

Mortalityrates are high in relapsed/refractory T-ALL, necessitating novel treatments toimprove survival. CD7, a T-cell antigen expressed in more than 95% of diseasesamples, represents a plausible target in this setting. GC027, which targetsCD7 and was developed using using lentivirus and CRISPR/Cas9, showed promise inmurine models for treating T-ALL.

For this single-arm, open-label study, researchers evaluated the safety and efficacy of GC027 in relapsed/refractory T-ALL. All included patients were between 18 and 70 years old, had a projected survival of more than 3 months, and had a performance status of 0 to 2. Patients with extramedullary disease or central nervous system involvement were not eligible to participate.

Fivemen (median age, 24 years) were enrolled in the trial. The median number ofprior lines of therapy was 5, no patients had undergone prior stem celltransplantation, and the median baseline bone marrow tumor burden was 38.2%.

All5 patients had a complete response or complete response with incomplete hematologicrecovery, and 4 of the 5 patients were minimal residual diseasenegative.

Allpatients also experienced grade 3 (4 patients) or 4 (1 patients) cytokinerelease syndrome; no grade 5 events of any kind were reported.

Witha single infusion of GC027, 80% of the patients had robust CAR-T cell expansionand achieved persistent [minimal residual diseasenegative complete response]without using any biologics as part of the preconditioning therapy or bridgingto [hematopoietic stem cell transplantation], the authors wrote.

Wang X, Li S, Gao L, et al. Safety and efficacy results of GC027: The first-in-human, universal CAR-T cell therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl): abstr 3013.

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GC027 Shows Promise as Therapy for Adult Relapsed, Refractory T-Cell ALL - Hematology Advisor

WASHINGTON, June 3, 2020 /PRNewswire/ --A new systematic review and meta-analysis of clinical studies using mesenchymal stromal cells (MSCs) led by a team at the Mayo Clinic, and including researchers from Emory, Duke, Case-Western, and the University of Miami, shows a trend toward improved outcomes and reduced mortality for patients with acute respiratory distress syndrome (ARDS), a major complication for patients with COVID-19. This studyand several othersalso have shown that MSCs are safe for patients.

Based on these findings, the authors call for the rapid commencement of large-scale, confirmatory clinical trials to build on the existing evidence base, which shows a trend toward improved pulmonary function and reduced severe lung inflammation for patients with ARDS, paving the way toward another treatment option for seriously ill patients with COVID-19.

To date, nearly two million Americans have tested positive for COVID-19 and more than 100,000 Americans have died. In its most severe form, COVID-19 leads to ARDSa life-threatening lung injury that allows fluid to leak into the lungs and makes it difficult for patients to breathe. More than 40 percent of individuals hospitalized for severe and critical COVID-19 develop ARDS, and 22 percent to 62 percent of those who are diagnosed and become critically ill, die from the disease. There is no effective treatment for ARDS today; MSCs potentially offer a unique therapeutic option to help patients in need.

"The analysis shows a positive trend in outcomes when treating ARDS patients with MSC therapy and represents the potential to save thousands of patients with COVID-19 induced ARDS," said Wenchun Qu, MD, PhD of the Mayo Clinic and first author of the paper. "The potential benefitcombined with the demonstrated safety of these therapiessupports the need for rapid commencement of more clinical trials."

"Acute respiratory distress syndrome is a rapidly progressive disease that can occur in critically ill patients," said Anthony Atala, MD, Editor-in-Chief of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. "Having additional potential therapies, such as MSCs, could be highly beneficial to patients with COVID-19."

To date, the FDA has approved more than a dozen investigational new drug applications for the use of MSCs for COVID-19-related conditions. The National Institutes of Health (NIH) has also supported the use of MSCs and other regenerative cell therapies to help patients with other conditions. The bipartisan 21st Century Cures Act provided $30 million in funding to the NIH over three years for clinical research for such therapies. However, these limited investments expire in fiscal year 2020.

The Alliance for Cell Therapy Now and the Regenerative Medicine Foundation support the recommendation of the authors, who urge funding for larger studies that build on the results to date. Collaboration and funding are also needed to collect and analyze the evidence from multiple ongoing and new studies, to better evaluate outcomes and potential benefits of MSC therapy for COVID-19 patients in need. A portion of the more than $10 billion in funding directed by Congress to the Biomedical Advanced Research and Development Authority (BARDA) and the NIH for COVID-19 should be used to support these goals.

About the Alliance for Cell Therapy Now

Alliance for Cell Therapy Now (ACT Now) is an independent, non-profit organization devoted to advancing the availability of and access to safe and effective cell therapies for patients in need. ACT Now convenes experts and stakeholders to develop and advance sound policies that will improve the development, manufacturing, delivery, and improvement of regenerative cell therapies. See http://allianceforcelltherapynow.org/

About the Regenerative Medicine Foundation

The non-profit Regenerative Medicine Foundation (RMF) fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF pursues its mission by producing its flagship World Stem Cell Summit, honoring leaders through the Stem Cell and Regenerative Medicine Action Awards, and promoting educational initiatives. STEM CELLS Translational Medicine is RMF's official journal partner. See https://www.regmedfoundation.org/

SOURCE Alliance for Cell Therapy Now

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MSC Therapy for Acute Respiratory Distress Syndrome; It's Time to Accelerate Clinical Trials for COVID-19 Patients in Need - PRNewswire

ALLO-501, an allogeneic CAR T-cell therapy, paired with ALLO-647, a monoclonal antibody, yielded high response rates and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell or follicular lymphoma, according to a first-in-human study presented at the 2020 ASCO Virtual Scientific Program.

The 2 treatments were used sequentially in the open-label, phase I ALPHA study that occurred at 6 U.S. sites, demonstrating an overall response rate (ORR) of 63%, including a 37% complete response rate in 19 evaluable, previously treated adults.

Researchers believe that allogeneic CAR T therapy, made from healthy donor T cells, can provide the benefits of autologous CAR T therapy while increasing patient access, the studys lead author, Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston, explained. He added that providing an off-the-shelf version of CAR T-cell therapy makes it available to patients more quickly, including on occasions when repeat dosing is necessary.

ALL0-501 is a genetically modified anti-CD19 CAR T-cell product in which the protein TCR alpha is disrupted to reduce the risk of graft-versus-host disease (GvHD). To support the effectiveness of the 2-pronged approach, the protein CD52 has been knocked out in ALLO-501 so that its partner therapy, the anti-CD52 monoclonal antibody ALLO-647, can be used successfully in lymphodepletion.

ALPHAs primary endpoint was the safety and dose-limiting toxicity of ALL0-647 followed by ALLO-501. A secondary endpoint was ORR.

Eligible participants had advanced disease, an ECOG status of 0 or 1 and had been treated with at least 2 previous lines of therapy. Prior treatment with an anti-CD20 monoclonal antibody or with autologous CAR T therapy was permitted, as long as the patients tumor remained CD19-positive.

A total of 22 patients, whose median age was 63 years, were treated. Approximately two-thirds had diffuse large B-cell lymphoma and the rest had follicular lymphoma. Approximately half had high-risk disease. Their median number of previous treatments was 4.

Patients underwent lymphodepletion that included fludarabine, cyclophosphamide and ALLO-647; 3 regimens of varying doses were tested, which included ALLO-647 doses of 39 mg and 90 mg. This was followed by infusion of ALLO-501 at CAR-T cell doses of 40 million, 120 million, or 360 million, Neelapu said.

All the medication in the trial was made from the T cells of a single healthy donor, he said.

At a median follow-up of 3.8 months, 63% of patients (n = 12) demonstrated a response to treatment (95% CI, 38%-84%), including 37% (n = 7) who had complete responses (95% CI, 16%-62%). Most patients experienced tumor shrinkage, Neelapu said. The median time until response was 1 month, and 9 patients continue to respond. One patient achieved a complete response after a second infusion of ALLO-501, Neelapu reported.

He noted that 10 of 16 patients evaluated to date showed evidence of CAR-T cell expansion, which was associated with better response.

No dose-limiting toxicity or GvHD was observed in any of the patients treated. The most common adverse events of grade 3 or higher were neutropenia (55.6%), leukopenia (33.3%), and anemia (22.2%). Seven patients developed cytokine release syndrome, 2 of them at grade 1, 4 at grade 2 and 1 at grade 3, all reversible without steroids or tocilizumab (Actemra), according to the researchers. About half the patients had infusion reactions, most grade 2 or lower. Eleven infections reported were grade 3 and lower, mostly asymptomatic and diagnosed during weekly monitoring, Neelapu said. Finally, 1 patient developed a grade 1 neurotoxicity that resolved without treatment.

Neelapu said the safety of the 2 drugs appears comparable to that of autologous CAR T products currently approved for use.

Researchers noted that higher doses of ALLO-647 could have a potential association with deeper responses, as a larger proportion of patients on the greater dose saw a complete response. Follow-up is ongoing as researchers seek to enroll more patients to test for further response.

Reference:

Neelapu SS, Munoz J, Locke FL, et. al. First-in-human data of ALLO-501 and ALLO-647 in relapsed/refractory large B-cell or follicular lymphoma: ALPHA study. Presented at: 2020 ASCO Virtual Scientific Program; May 29, 2020. Abstract 8002.

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Off-the-Shelf CAR T-Cell Therapy Shows Promise in Relapsed/Refractory B-Cell Lymphomas - Cancer Network

Atara Biotherapeutics cell-based therapy ATA188 is safe and well-tolerated in people with progressive forms of multiple sclerosis (MS), and induces a sustained reduction in disability in a dose-dependent manner, findings from the first part of a Phase 1 clinical trial show.

ATA188 had an acceptable safety and tolerability profile across all four doses tested. But more people on higher doses experienced sustained decreases in disability, and researchers chose the 20 million dose (the second highest dose) for further testing in this trials second part.

Patient enrollmentfor this randomized, placebo-controlled part two is again underway at sites in the U.S. and Australia after atemporary pause inresponse to theCOVID-19 pandemic, the company said in a press release.

The new data were presented at the2020 European Academy of Neurology (EAN) Congress which was held virtually due to the pandemic in the poster Phase 1 study of the safety and efficacy of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy to treat progressive forms of multiple sclerosis (EAN registration is needed to access the presentations).

Infection with theEpstein-Barr virus (EBV, a common form of the herpes virus) is increasingly seen as a possible cause of MS, leadingB-cellsto go rogue and produce antibodies that wrongly attack the protective myelin coating of nerve cells.

ATA188 is designed to help patients get rid of these damaging B-cells, by providing them with T-cells (immune cells with the ability to fight threats) that have been modified to eliminate EBV-infected cells.

The ongoing Phase 1a/1b trial (NCT03283826) is assessing the safety and effectiveness of ATA188 in a near equal mix of patients with either primary progressive MS (PPMS) or secondary progressive disease (SPMS).

It is being conducted in two parts. First, 25 patients were given one of four ATA188 doses 5 million (5 x 106), 10 million (1 x 107), 20 million (2 x 107), or 40 million (4 x 107) cells to determine the safest and most effective dose for future testing. The first three dose groups had six patients; in the fourth group, seven patients received the 40 million dose.

Treatment was administered in two cycles, with three ATA188 injections each, with patients evaluated after treatment initiation at three, six, and 12 months. These people could then enter an extension part of the trial, and receive once-a-year ATA188 intravenous (IV) injections for up to four years.

Part ones main goal was to assess treatment safety and tolerability. Secondary measures include changes in disability scores, assessed with the expanded disability status scale (EDSS) and timed 25 foot walk (T25FW; time taken to safely walk 25 feet).

Results here showed that the treatment was safe and well-tolerated across all four dose groups, with runny nose being the only treatment-related side effect reported in more than one person.

There was no evidence of cytokine release syndrome(a systemic inflammatory response),graft versus host disease (a complication in which healthy cells are attacked by transplanted T-cells), or dose-limiting toxicities.

Potential treatment efficacy was assessed using a composite measure of sustained disability improvement (SDI), defined as clinically significant improvements in either EDSS or T25FW scores. These improvements had to be sustained, meaning that patients needed to show improvements at two consecutive time points.

In other words, a patient had SDI at six months if improvement in disability scores was seen at three months and confirmed at six months. For SDI at one year, patients had to show improvements at month six and confirm them at the 12-month evaluation.

Researchers found that one patient on the 5 million dose, one on the 10 million dose, and two patients on the 20 million dose group achieved SDI at six months, and that all maintained those improvements at one year. A third patient on the 20 million cells per dose also achieved SDI at 12 months.

Two patients on the highest 40 million dose also reached SDI at six months, but 12-month assessments are not yet complete in this group.

Most patients achieved SDI due to clinical improvements in EDSS, researchers reported.

An additional outcome measure, based on several validated MS scales, was used to help categorize outcomes on a range from clinical decline to clinical improvement. Those patients who achieved durable clinical improvements on SDI measures also experienced a clinical improvement using this outcome measure.

With dose increases, more patients again showed clinical improvements on this scale, and fewer of them experienced clinical decline.

The approach of targeting EBV-infected B cells has led to very encouraging preliminary results, as ATA188 proved to be safe and well-tolerated across all four dose cohorts in this Phase 1a study, Lawrence Steinman, MD, a professor at Stanford University, said in the release.

These results, along with the observed trend in sustained disability improvements seen at six months and maintained at 12 months, highlight the opportunity to advance into the randomized placebo-controlled study of ATA188 for the treatment of patients with progressive MS, Steinman added.

Researchers are now testing the recommended20 million dose in the trials second part, which will randomly assign a new group of adults with progressive MS to ATA188 or a placebo.

Treatment goals here are to continue studying safety and effectiveness, and to establish ATA188s superiority over a placebo in a number of measures, including disability progression, cognition, fatigue, changes on MRI scans, and biological factors.

If these data are confirmed in a double-blind, placebo-controlled, randomized study, we could see an evolution in the treatment paradigm for progressive MS and other forms of this debilitating disease, Steinman said.

We look forward to the continued study of ATA188 in progressive MS, and believe our novel therapeutic approach targeting the EBV-infected B cell as a propagator of autoimmunity may help patients with other forms of MS, said AJ Joshi, MD, senior vice president and chief medical officer of Atara Biotherapeutics.

Among other disorders being also considered are autoimmune conditions where EBV has been implicated, including lupus, rheumatoid arthritis, and Sjgrens syndrome, Joshi added.

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Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Progressive MS Cell Therapy, ATA188, Safe and Lessens Disability, Trial Reports - Multiple Sclerosis News Today

NEW YORK, June 03, 2020 (GLOBE NEWSWIRE) -- Cytovia Therapeutics, Inc (Cytovia), an emerging biopharmaceutical company developing Natural Killer (NK) immunotherapies for cancer, today announces the appointment of Dr. Wei Li as acting Chief Scientific Officer (CSO), effective June 1, 2020.

During her biotech career, Dr. Li co-founded two companies and built up extensive expertise in all aspects of drug research and development, including preclinical development and pharmacology, clinical development and operations, regulatory affairs, biomarker development and biomanufacturing.

Most recently, Dr. Li was Chief Development Officer at OliX Pharmaceuticals, a leading public South Korean biotech company developing siRNA therapeutics for multiple indications. She also served as Executive Vice President, Product Development at Boston Biomedical, Inc (BBI) from 2007-2018, playing a key role in growing it from a start-up in 2007 to an industry leader in cancer stem cell research, including through the acquisition by Sumitomo Dainippon in 2012. Dr. Li led the development of napabucasin (BBI608), a first-in-class drug selected as one of the worlds top ten cancer drugs in late stage clinical development by Fierce Biotech. Dr. Li started her career at ArQule, a public biotech company developing targeted therapies for hematological malignancies and acquired by Merck &Co in 2019.

Wei Li holds a PhD in Molecular Virology from Georgia State University and completed her Postdoctoral Training at Harvard Medical School.

Dr. Wei Li said: I am thrilled to be joining the great team of scientists and entrepreneurs at Cytovia Therapeutics. NK-cell based therapeutics are at an inflection point. Initial clinical trials have shown promising safety and efficacy. Off-the-shelf manufacturing promises broader and faster patient access. Cytovia Therapeutics has an excellent iPSC CAR-NK platform and a strong pipeline in both hematological and solid tumors. It is tremendously exciting to be involved in this stage of the companys development.

Dr Daniel Teper, co-founder, Chairman and CEO of Cytovia Therapeutics, Inc said: We are delighted to welcome Dr. Wei Li to Cytovia Therapeutics as Chief Scientific Officer. Wei has a stellar track record of bringing innovative oncology drugs from discovery to clinical development. Her operational excellence and entrepreneurial drive will be critical to help bring multiple iPSC CAR NK therapeutics to initial clinical trials starting in 2021.

ABOUT CYTOVIA THERAPEUTICS, INCCytovia Therapeutics is an emerging biotechnology company that aims to accelerate patient access to transformational immunotherapies, addressing several of the most challenging unmet medical needs in cancer and severe acute infectious diseases. Cytovia focuses on Natural Killer (NK) cell biology and is leveraging multiple advanced patented technologies, including an induced pluripotent stem cell (iPSC) platform for CAR (Chimeric Antigen Receptors) NK cell therapy, next-generation precision gene-editing to enhance targeting of NK cells, and NK engager multi-functional antibodies. Our initial product portfolio focuses on both hematological malignancies such as multiple myeloma and solid tumors including hepatocellular carcinoma and glioblastoma. The company partners with the University of California San Francisco (UCSF), the New York Stem Cell Foundation (NYSCF), the Hebrew University of Jerusalem and Macromoltek.

Learn more at http://www.cytoviatx.com

Contact for media enquiries at Cytovia Therapeutics, IncSophie BadrVP corporate AffairsSophie.badre@cytoviatx.com1(929) 317 1565

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Cytovia Therapeutics, Inc appoints Dr. Wei Li as Chief Scientific Officer to accelerate the development of iPSC CAR-NK Cell Therapy for Cancer -...

Patients with relapsed or refractory indolent non-Hodgkin lymphoma who were treated with the chimeric antigen receptor (CAR) T-cell therapy of axicabtagene ciloleucel (axi-cel; Yescarta) had high rates of complete response (CR) and demonstrated the agent's manageable safety profile, according to an interim analysis of the phase 2 ZUMA-5 study (NCT03105336) presented as part of the 2020 American Society of Clinical Oncology Virtual Scientific Program.1

Axi-cel yields high rates of response in indolent B-cell non-Hodgkin lymphoma, Caron A. Jacobson, MD, of the Dana-Farber Cancer Institute, said during a presentation of the data. Although longer follow-up is needed, these responses appear to be durable amongst follicular lymphoma patients.

Adults with relapsed or refractory follicular lymphoma (FL; grades 1-3a) and marginal zone lymphoma (MZL; nodal or extranodal) after 2 lines of therapy (including an anti-CD20 monoclonal antibody [mAb] with an alkylating agent), and an ECOG status of 0 or 1 were eligible for the study. Participants were leukapheresed and received conditioning chemotherapy followed by axi-cel infusion at 2 106 CAR T-cells/kg.

Of the 96 patients evaluable for efficacy, the objective response rate (ORR) was 93% (95% CI, 86%-97%) and the CR rate was 80% (95% CI, 71%-88%). The median time to first response was 1 month (range, 0.8-3.1). More specifically, patients with FL (n = 80) had an ORR of 95%, with an 81% CR rate, and those with MZL (n = 16) had an ORR of 81% with a 75% CR rate.

With a median follow-up of 15.3 months, the estimated duration of response (DOR) in all patients was 20.8 months, and 68% of patients with FL had an ongoing response as of the data cut-off. Moreover, the median PFS was 23.5 months (95% CI, 22.8 - not evaluable) in all patients, and the median overall survival (OS) was not reached. However, the 12-months OS rate was 94.3% (95% CI, 86.8-97.6) for all patients.

These interim results suggest that axi-cel may be a promising approach for treating this patient population.

The primary endpoint of the study was ORR by central review. Key secondary endpoints included DOR, progression-free survival (PFS), OS, safety, and blood levels of cytokines and CAR T-cells.

As of December 16, 2019, 140 patients (FL, n = 124; MZL, n = 16) had received axi-cel with a median follow-up of 15.3 months (range, 1.9-28.8). The median age of the participants was 63 years of age (range, 34-79), 49% of patients were male, 52% had stage IV disease, 51% had 3 FLIPI, and 49% had high tumor bulk (GELF). Moreover, patients had a median 3 prior lines of therapy, 66% progressed < 2 years after initial anti-CD20 mAb-containing therapy (POD24), and 73% were refractory to the last prior treatment.

All of the study participants were evaluable for safety, and 119 patients (85%) experienced grade 3 adverse events (AEs). The most commonly observed AEs were neutropenia (34%) and anemia (22%). Additionally, grade 3 cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 8% and 17% of patients, respectively. There were only 2 grade 5 AEs, including multisystem organ failure in the context of CRS (related to axi-cel) and aortic dissection (unrelated to axi-cel).

Given the long natural history of these diseases, safety is of paramount importance, Jacobson said. The safety profile was manageable and reversible, and appeared to be at least similar to that of axi-cel in aggressive lymphomas.

The median time to peak of anti-CD19 CAR T-cell levels after axi-cel infusion was 8 days (range, 8 - 371). Furthermore, anti-CD19 CAR T-cells were detectable at 18 months in most patients with evaluable samples (13/15 [87%]).

Notably, in patients with FL, peak CAR T-cell expansion was associated with both grade 3 CRS (P = 0.0088) and neurologic events (P = 0.0076). In addition, peak serum analyses across multiple immune programs were associated with grade 3 CRS, grade 3 neurologic events, or both in patients with FL.

This may have implications for the possibility of outpatient therapy for this disease in the future, said Jacobson.

Axi-cel appears to be a promising therapeutic approach for patients with relapsed and refractory indolent B-cell non-Hodgkin lymphoma.

Axi-cel is currently approved by the FDA as a treatment for adult patients with relapsed or refractory large B-cell lymphoma based on findings from the phase II ZUMA-1 trial.2 The agent is indicated specifically following 2 prior therapies for those with diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma (TFL).

References

<< View more of Targeted Oncology's coverage from the 2020 ASCO Virtual Annual Meeting

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CAR T-Cell Therapy With Axi-Cel Holds Promise in R/R Indolent NHL - Targeted Oncology

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Cart Cell Therapy Market 2020 Global Outlook, Research, Trends and Forecast to 2028| Novartis AG, Kite... - Azizsalon News