Jasper Therapeutics Raises $35M in Series A Financing – FinSMEs

Jasper Therapeutics, Inc., a Palo Alto, Calif.-based new biotechnology company, raised $35m in Series A financing.

The round was led by Abingworth LLP and Qiming Venture Partners USA with further investment from Surveyor Capital (a Citadel company) and participation from Alexandria Venture Investments, LLC.

Jasper Therapeutics is a biotechnology company focused on enabling safer conditioning and therapeutic agents that expand the application of curative hematopoietic stem cell transplants and gene therapies.

The company intends to use the funds to advance the clinical development of its lead product candidate, JSP191, which is designed to replace or reduce the toxicity of chemotherapy and radiation therapy as a conditioning regimen to prepare patients for hematopoietic cell transplant.Jaspers development of JSP191 is also supported by a collaboration with the California Institute for Regenerative Medicine (CIRM), which has been funding the program and is committed to providing a total of $23 million in grant support. As part of the Series A financing, Amgen, which discovered JSP191 (formerly AMG191), has licensed worldwide rights to Jasper that also include translational science and materials from Stanford University.

Jasper was co-founded by Judith Shizuru, M.D., Ph.D., a hematopoietic stem cell transplant expert at Stanford University, and Susan Prohaska, Ph.D., a Stanford University-trained immunologist, stem cell biologist and early-stage drug development professional. Dr Shizurus CIRM-funded lab advanced the understanding of the ability of anti-CD117 to impact hematopoietic stem cells and, together with the Lucile Packard Childrens Hospital Stanford and University of California, San Francisco (UCSF) pediatric transplant teams, was the first to study an anti-CD117 antibody in the clinic as a conditioning agent.That humanized antibody, now called JSP191, was first studied for conditioning for transplant in immune-deficient patients in collaboration with Amgen, UCSF and CIRM.

JSP191 is currently being evaluated in an ongoing Phase 1 clinical trial as a conditioning agent to enable stem cell transplantation in patients with severe combined immunodeficiency (SCID) who received a prior stem cell transplant that failed.

The founding management team of the company includes: William Lis, Executive Chairman and Interim Chief Executive Officer (CEO), Jeet Mahal, M.B.A., M.E., M.B., Chief Financial Officer and Chief Business Officer, Susan Prohaska, Ph.D., Co-Founder and Vice President of Operations & Program Management, Wendy Pang, M.D., Ph.D., Executive Director, Discovery Research, and Early Clinical Development, Robert Sikorski, M.D., Ph.D., Executive Consultant and Acting Chief Medical Officer.

Dr. Shizuru and Mr. Lis are joined on the Jasper Therapeutics Board of Directors by Kurt von Emster, Managing Partner of Abingworth LLP, and Anna French, Ph.D., Principal at Qiming Venture Partners USA. Dr. Prohaska is a Board observer.



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Jasper Therapeutics Raises $35M in Series A Financing - FinSMEs

Addressing Disparities in Cancer: Factors Influencing Care, Access and Outcomes – OncoZine

In their March 2006 report, the Institute of Medicine (IOM) showed overwhelming evidence of the existence of health related disparities for racial and ethnic minorities. The reports definition of cancer health related disparities refers to the unequal treatment of patient population groups the difference in treatment or access not justified by the differences in health status or preferences of the groups on the basis of race, ethnicity, and sometimes on the basis of gender, socioeconomic status, age or other patient characteristics.[1]

Over the last decade multiple medical societies and governmental agencies have studied the cause of cancer health disparities as well as attempted to identify solutions to the problem.

Five different studies being presented during the 61st annual meeting of the American Society of Hematology (ASH), held December 7 10, 2019 in Orlando, Florida, paint a mixed portrait of how demographics and socioeconomic status affect access to clinical trials and effective treatments for patients with blood cancers.

Some studies show encouraging evidence that racial minorities and older patients receive similar benefits compared to cancer treatments other patient groups receive. However, other studies show that their are still significant gaps in terms of care access and outcomes, underscoring the urgent need for renewed efforts to address disparities.

Inclusion is not only the right thing to do for our patients and our community its also the right thing to do if our goal is to create medicines that are truly targeted, noted Laura Michaelis, MD, Medical College of Wisconsin.

Clinical trialsBut the studies go beyond traditional healthcare. What is, for example, the impact of clinical trial inclusion criteria on cancer health disparities?

Based on data from a number of clinical trials, inclusion and exclusion criteria can become too restricting, limiting patient access. Other studies demonstrate that some of these criteria may result in the systematic exclusion minorities and older patients.

Our ability to achieve tailored treatments and prevention relies on including a wide and heterogeneous spectrum of individuals in clinical trials, Michaelis noted.

We have an obligation to recruit people who are traditionally absent from trials, including groups such as women, older people, minorities, people living in poverty, and people who are chronically ill or who have comorbidities, she concluded.

Socioeconomic Disparities in Survival of ChildrenA study by Lena E. Winestone, MD, MSHP and colleagues, at UCSF Benioff Childrens Hospital in San Francisco, shows that children from poorer neighborhoods were 2.4 times more likely to die during treatment for acute myeloid leukemia or AML than children from middle and high-income neighborhoods. [2]

The results of the study, funded by National Institutes of Health/National Cancer Institute (NIH/NCI), are based on an analysis of nearly 1,500 clinical trial participants. While previous research has pointed to racial disparities in cancer survival, the new study is the first to identify socioeconomic status as a key contributor to disparities among children with AML who were enrolled in clinical trials.

These findings are especially alarming because clinical trials are designed to provide consistent treatment across all participant groups. The fact that disparities were found despite the rigorous setting of clinical trials suggests that these disparities arise from a variety of factors outside of the specific chemotherapeutic therapy used.

We expected there to be a difference, but the degree of difference is quite substantial, Winestone, who is the lead study author, noted.

The more people are cognizant about the disparities that exist, the better positioned well be to ameliorate them, he added.

Researchers at UCSF Benioff Childrens Hospital and the Childrens Hospital of Philadelphia examined clinical trial data from children enrolled on two recent AML trials, AAML1031/NCT01371981 and AAML0531/NCT01407757, and used U.S. Census data to determine the median income and educational attainment in patients neighborhoods. [2]

They found that neighborhood socioeconomic factors were significant predictors of survival, even after accounting for insurance type, race, and known biologic risk factors.

While about 68% of patients from middle or high-income areas survived for five years following diagnosis, that proportion was 61% among patients from low-income areas and just 43% among patients living in poverty.

A significantly higher proportion of Black and Hispanic patients lived in poverty, low income, and low education areas. Researchers found that the racial disparity persisted even after accounting for neighborhood socioeconomic factors, suggesting Black patients face a significantly higher risk of death than white children living in areas of the same socioeconomic level.

The study did not determine the reasons behind the increased risk of death.

However, Winestone noted that one possibility is that toxic stress, which has been linked with lower socioeconomic status, may impact responses to chemotherapy or immune recovery following chemotherapy.

The researchers plan to further examine when patients died and the cause of death in the hopes of gaining insights as to whether the risks are connected to treatment-related causes or to the cancer itself.

Winestone also pointed out that in addition to drawing attention to persistent racial and socioeconomic disparities in cancer outcomes, the results also highlight potential additional data to be collected as part of clinical trials.

Rather than relying on neighborhood data as a proxy, she explained, it would be helpful if future clinical trials collected individual data on participants socioeconomic status at the time of enrollment.

If we could gather that information, it would allow us to dig deeper into the question of how someones circumstances outside of the clinical aspects of their disease impact their health outcomes, Winestone concluded.

Racial Disparities and comorbidities and/or organ dysfunctionA study of more than 1,000 patients with AML revealed that African Americans were more likely to have evidence of abnormal kidney functioning than whites, but this was not associated with any difference in overall survival. [3]

The findings have implications for the design of clinical trials, which typically exclude patients with signs of kidney dysfunction and may, as a result, disproportionately, and unnecessarily, exclude minorities from participating in clinical trials.

Its important that we understand how drugs work in different patient populations in clinical trials, especially those that reflect the patients we will eventually treat with the drug, said lead study author Abby Statler, Ph.D, of Cleveland Clinic.

Designers of clinical trials can use data from studies like ours to inform future eligibility criteria in order to test drugs in more diverse populations, Statler further noted.

Clinical trials test the effectiveness of new treatments and identify any safety concerns before a drug can be sold on the market. Trials often seek to enroll patients who have only a few health problems (called comorbidities)other than the one being studied. This approach makes it easier to tell if study outcomes are related to the use of the experimental drug rather than influenced by a patients other health conditions or medications. However, because patients in racial minorities may, on average, have more comorbidities, this practice may disproportionately exclude these individuals from clinical trials. As a result, the population of trial participants does not reflect the real-world diversity of the patient population who will ultimately receive the investigational drug following regulatory approval.

In this study, researchers examined health records from 1,040 AML patients receiving care at Cleveland Clinic from 2003-2019. They found no significant differences between African American and white patients in treatment approaches, rates of responsiveness to treatment, or overall survival, suggesting that treatments worked just as well in African Americans as whites.

However, the study demonstrated that African Americans were significantly more likely to have abnormal creatinine and creatinine clearance, signs that the kidneys are not clearing waste products from the bloodstream as effectively as they should. However, this abnormality may be benign, as previous studies suggest African Americans have higher creatinine levels than whites. Consequently, this laboratory value may falsely underestimate this subpopulations kidney function, causing them to fail study enrollment requirements that require normal creatinine or creatinine clearance values.

The researchers observed that patients with minor creatinine or creatinine clearance abnormalities showed no differences in overall survival. This, they noted, calls into question the necessity of excluding patients with these abnormalities from AML trials.

The study, Statler noted, also bolstered evidence that African Americans may simply have higher baseline creatinine levels than white patients.

These findings suggest trials might be able to broaden their criteria to include patients with kidney disease without compromising the safety of the participants, said Statler.

In doing so, we might be able to truly improve the number of patients from minority populations who are potentially eligible for trials but who would have been excluded for that reason alone, she said.

The study also examined markers for a variety of comorbidities including endocrine, gastrointestinal, liver, cardiovascular, and neurological functioning. Of these, liver dysfunction was the only comorbidity that was associated with diminished survival. The researchers plan to further examine the data to determine precise kidney function cutoff points for future clinical trial eligibility criteria.

Statler concluded that in addition to AML the study findings could be relevant to designing trials for other cancers, particularly prostate cancer, which disproportionately affects African American men.

A Hands-On ApproachA study of 182 patients treated for diffuse large B-cell lymphoma (DLBCL) at a safety net cancer center reports that non-white patients had similar health outcomes to white patients. The findings contrast previous population-based studies pointing to racial disparities in lymphoma outcomes and suggest possible steps tertiary centers can take to help close the gap. [4]

Researchers at the Levine Cancer Institute study found no significant differences between racial groups in terms of overall survival or survival without disease progression at two years. Racial groups also had similar rates of relapse, stem cell transplantation, and clinical trial enrollment. While the study does not indicate a specific reason for the lack of disparities, researchers suggest historically underserved patients may have benefited from hands-on assistance through the institutions patient navigator program, which was used by 85% of patients in the study.

The scientific literature shows that racial minorities tend to have poorer outcomes in lymphoma and several other diseases, and we wanted to know if that holds true at our institution, said senior study author Nilanjan Ghosh, MD, Ph.D, of Levine Cancer Institute.

We found that minorities do not have worse outcomes for DLBCL if the disease is optimally managed, which requires that all patients have access to care. It shows that if you work on addressing socioeconomic barriers, you can get equal results.

The centers patient navigator program is designed to help patients address logistical barriers to keeping appointments and staying on track with their cancer treatment.

For example, navigators can help patients who are homeless take advantage of lodging that is available for patients undergoing cancer treatment. They can also help arrange transportation for patients without a car. And navigators can help coordinate care across providers such as primary care physicians, oncologists, and other specialists.

Analyzed data related to patients treated for newly diagnosed DLBCL between 2016-2019, the researchers noted that about four out of five patients identified themselves as white. On average, 73% of non-white patients identifying themselves as African American and 15% identified as Hispanic.

White patients were significantly more likely to have private health insurance and less likely to have government insurance or no insurance than non-whites. In addition, white patients were slightly older than non-white patients.

Despite the differences in health insurance type, the researchers also found that white and non-white had similar rates of overall survival (74% and 81%, respectively) two years after diagnosis, as well as similar rates of progression-free survival (60% and 63%, respectively). Treatment regimens and outcomes for those with relapsed or refractory DLBCL were, according to the researchers, also similar among groups.

Age Should Not Be a BarrierEven though autologous hematopoietic cell transplantation (AHCT), a form of stem cell therapy, is an effective treatment for multiple myeloma, only four out of 10 patients receive this therapy. A new study by Anita DSouza, MD, Medical College of Wisconsin, and colleagues demonstrated that AHCT is safe and effective in older patients and suggests that more people could benefit from the therapy than have typically been offered it. [5]

Older people are often excluded from clinical trials studying transplant because they tend to have a greater number of health issues. Without trials proving newer, aggressive treatments are safe for older patients, doctors may avoid them on the assumption that they are too risky. In addition to showing AHCT is safe and effective in patients over 70 years of age. The researchers also found patients fared better when given the conditioning chemotherapy drug melphalan (Alkeran) in the normal dose of 200 mg/m2, rather than the reduced dose of 140 mg/m2 often given to older patients.

This study shows that you can perform these transplants safely in older patients, and the older patients get the same benefits from these treatments as the younger patients do, DSouza, who is the studys lead author, noted.

In addition, if there are no contraindications other than simply age, its worth trying the higher dose of melphalan. Age alone should not be a reason to automatically reduce the dose, DSouza added.

According to DSouza, the study strengthens the argument that people should not just be excluded from clinical trials based on age alone. Multiple myeloma is the second most common blood cancer, and it occurs most often in older adults. Half of patients are age 70 or older at the time of diagnosis.

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, the researchers examined health records of approximately 16,000 patients who received AHCT with melphalan in the United States between 2013-2017.

After adjusting for factors such as functional status, comorbidities, and disease stage, they found patients who received their treatments at age 70 or older had similar rates of relapse or disease progression, progression-free survival, and death not caused by a cancer relapse as those 60-69 years of age.

Of patients age 70 and older, about 40% received the full dose of melphalan and 60% received a reduced dose. Those receiving the reduced dose had significantly worse outcomes and lower survival rates. However, DSouza noted that it is impossible to determine whether these patients were also more frail to begin with, in which case their poorer outcomes would not necessarily be due to the dosing reduction.

While AHCT specialists often support the use of AHCT in otherwise healthy older patients, DSouza noted that oncologists in community hospitals where many patients are first treated often fail to refer older patients to transplant centers. The researchers noted a significant increase in the proportion of older patients receiving AHCT in 2017 compared to 2013, suggesting that referrals to AHCT specialists increased over time.

In addition to age disparities, the study also speaks to important racial disparities in the care of patients with myeloma, a disease which is twice as common in African Americans as whites. Yet AHCT rates are significantly lower among black patients, which made DSouza concluded that age likely adds to the barriers for these patients.

CAR T-cell therapy Reduces Health Care Utilization in Older PatientsA new analysis of Medicare claims data offers the first real-world evidence using claims data available after the approval of autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, a type of immunotherapy. [6]

These analyses, Karl M. Kilgore, Ph.D, of Avalere Health observed, shows that CAR T-cell therapy may be beneficial for a broad population of older patients with DLBCL, including those with multiple chronic conditions. The research also shows patients spent less time in the hospital and had lower health care costs after CAR T-cell therapy than they did in the months leading up to it.

The U.S. Food and Drug Administration (FDA) approved the first CAR T-cell therapy for adults with DLBCL in 2017. However, many of the patients included in the clinical trials leading up to that approval were middle-aged, with a median age of 56-58. This study used the earliest available Medicare claims data to assess the treatments use in Medicare patients age 60 and older, who comprise the majority of Medicare beneficiaries and often have multiple chronic health issues.

Our findings offer evidence that older patients with multiple comorbidities can be treated successfully with CAR T-cell therapy, Kilgore, who is the lead study author, said.

While we dont know the long-term outcomes yet, nearly three-quarters of the patients were still alive six months post-treatment. Even in that narrow window of time we saw a significant decline in health care utilization including hospitalizations and emergency room use, which is suggestive of a successful course of treatment, Kilgore concluded.

DLBCL, a cancer that starts in the white blood cells, accounts for about one-third of the 74,000 cases of non-Hodgkin lymphoma diagnosed in the United States each year. About 63% of patients survive for five years after their diagnosis. For those who relapse or have refractory disease, treatment options include chemotherapy, stem cell transplantation, and CAR T-cell therapy. CAR-T works by re-engineering a patients own T-cells, part of the immune system, to kill cancer cells. Multiple steps are required to collect, modify, and re-infuse T-cells into the patient, a process that is typically combined with lympho-depleting chemotherapy and a single infusion of the patients modified T-cells.

The researchers analyzed claims data from patients enrolled in Medicare Fee For Service parts A and B October 2017-September 2018. They identified 207 patients with an average age of 70 years who had undergone CAR T-cell therapy for DLBCL. Half underwent CAR T-cell therapy as part of a clinical trial, while the remainder had comorbidities that likely would have excluded them from CAR T-cell clinical trials.

Comparing health care utilization in the six months before and after CAR-T therapy, the researchers found patients average overall health care costs dropped by 39% after undergoing CAR-T, excluding the cost of the CAR-T treatment itself. In the months following CAR-T, patients spent less time in the hospital and had half as many emergency department visits than before the therapy.

Only 7.2% had any evidence of subsequent chemotherapy in the claims data, suggesting that the cancer had not returned within the first six months following CAR T-cell therapy for most patients.

Clinical trialsBortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia NCT01371981Study of Gemtuzumab Ozogamicin Therapy in DNA Samples From Patients With Acute Myeloid Leukemia Treated on COG-AAML0531 NCT01407757

Reference[1] McGuire TG, Alegria M, Cook BL, Wells KB, Zaslavsky AM. Implementing the Institute of Medicine definition of disparities: an application to mental health care. Health Serv Res. 2006;41(5):19792005. doi:10.1111/j.1475-6773.2006.00583.x [Abstract][2] Winestone LE, Getz KD, Bona KO, Fisher BT, Gamis AS, Seif AE, Sung L, Wang YC, Alonzo TA, and Aplenc R. Area-Based Socioeconomic Disparities in Survival of Children with Newly Diagnosed Acute Myeloid Leukemia: A Report from the Childrens Oncology Group. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 906. Outcomes ResearchMalignant Conditions (Myeloid Disease): Quality of Life, Late Effects, and Prognostic Factors in Myeloid DiseasesHematology Disease Topics & Pathways: Diseases, AML, Pediatric, Study Population, Clinically relevant, Myeloid Malignancies. [Abstract][3] Statler A, Hobbs BP, Radivoyevitch T, Mukherjee S, Bell K, Advani AS, Gerds AT, Nazha A, Patel BJ, Carraway HE, and Sekeres MA. Are Racial Disparities in Acute Myeloid Leukemia (AML) Clinical Trial Enrollment Associated with Comorbidities and/or Organ Dysfunction? 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 903. Health Services ResearchMalignant Conditions (Myeloid Disease): Cancer Care Delivery and Quality of Life in Myeloid Malignancies | Hematology Disease Topics & Pathways: Diseases, AML, Adult, Study Population, Myeloid Malignancies [Abstract][4] Hu B, Chen T, Boselli D, Bose R, JSymanowski JT, Raghavan D, Soni A, Park SI, Avalos BR, Copelan EA, Jacobs R, Ghosh N. Minorities Do Not Have Worse Outcomes for Diffuse Large B Cell Lymphoma (DLBCL) If Optimally Managed. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral. Session: 905. Outcomes ResearchMalignant Conditions (Lymphoid Disease): Mountains Conquered, Challenges Remain: Survivorship and Disparities in the Hematologic Malignancies. Hematology Disease Topics & Pathways: Adult, Diseases, Non-Hodgkin Lymphoma, DLBCL, Study Population, Clinically relevant, Lymphoid Malignancies, Quality Improvement.[Abstract][5] Munshi PN, Hari P, Vesole DH, Jurczyszyn A, Zaucha J, Davila O, Kumar SK, Shah ND, Qazilbash MH, DSouza A. Breaking the Glass Ceiling of Age in Transplant in Multiple Myeloma. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: Oral Session: 731. Clinical Autologous Transplantation: Results: Autologous Stem Cell Transplantation: Lymphoma and Plasma Cell Disorders | Hematology Disease Topics & Pathways: Adult, Study Population. [Abstract][6] Kilgore KM, Mohammadi I, Schroeder A, Teigland C, Purdum A, Shah GL. Medicare Patients Receiving Chimeric Antigen Receptor T-Cell Therapy for Non-Hodgkin Lymphoma: A First Real-World Look at Patient Characteristics, Healthcare Utilization and Costs. 61st annual meeting of the American Society of Hematology. Program: Oral and Poster Abstracts. Type: OralSession: 905. Outcomes ResearchMalignant Conditions (Lymphoid Disease): CAR T and Novel Therapies Coming of Age: Real-World and Patient-Centered Outcomes. Hematology Disease Topics & Pathways: Diseases, Biological, Therapies, CAR-Ts, Non-Hodgkin Lymphoma, DLBCL, Lymphoid Malignancies. [Abstract]

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Addressing Disparities in Cancer: Factors Influencing Care, Access and Outcomes - OncoZine

Fate Therapeutics Announces New Preclinical Data for FT596 Off-the-Shelf, iPSC-derived CAR NK Cell Cancer Immunotherapy – Benzinga

FT596 as a Monotherapy Demonstrates Comparable Anti-tumor Activity to CAR19 T Cells In Vivo in Humanized Mouse Model of Lymphoma

Combination of FT596 with Rituximab Shows Durable Tumor Clearance In Vivo in Preclinical Lymphoma Model

Company Plans to Initiate Enrollment of First-in-human Clinical Trial of FT596 in Early 2020

SAN DIEGO, Dec. 08, 2019 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, announced new in vivo preclinical data for FT596, its off-the-shelf, multi-antigen targeting natural killer (NK) cell product candidate derived from a clonal master engineered induced pluripotent stem cell (iPSC) line. The data were featured during the 61st American Society of Hematology (ASH) Meeting and Exposition as part of the organization's CAR-T and Beyond press program, which spotlighted promising next-generation cancer immunotherapies having the potential to overcome the key limitations of patient-specific chimeric antigen receptor (CAR) T-cell therapy.

"Current patient- and donor-specific CAR T-cell immunotherapies recognize only one antigen and fail to address the significant risk of relapse due to antigen escape. FT596 is ground-breaking in that it is designed to be available off-the-shelf for timely patient access and to promote deeper and more durable responses by targeting multiple tumor-associated antigens," said Bob Valamehr, Ph.D., Chief Development Officer of Fate Therapeutics. "Additionally, since FT596 is manufactured from a renewable master engineered iPSC line, the complexities of patient-by-patient genetic engineering and production are greatly reduced and, for the first time, we are able to mass produce multi-functional cellular immunotherapies in a uniform and cost-effective manner."

FT596 is the first cellular immunotherapy engineered with three active anti-tumor components to be cleared for clinical investigation by the FDA. In addition to a proprietary CAR targeting CD19, FT596 expresses a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor that has been modified to augment antibody-dependent cellular cytotoxicity, enabling coincident targeting of CD19 and additional tumor-associated antigens such as CD20. FT596 also expresses an interleukin-15 receptor fusion (IL-15RF), a potent cytokine complex that promotes survival, proliferation and trans-activation of NK cells and CD8 T cells without the need for systemic cytokine support. Together, these features of FT596 are intended to maximize potency and minimize toxicity in treated patients. The Company plans to initiate enrollment of a first-in-human clinical trial of FT596 in early 2020.

New preclinical data presented at ASH showed that FT596 administered as a monotherapy exhibited durable tumor clearance and extended survival in vivo similar to primary CAR T cells in a humanized mouse model of CD19+ lymphoma. Additionally, when combined with the anti-CD20 monoclonal antibody rituximab, FT596 showed enhanced killing of CD20+ lymphoma cells in vivo as compared to rituximab alone. These data confirm previously presented in vitro findings that demonstrate the unique multi-antigen targeting functionality of FT596, and the product candidate's potential to effectively overcome CD19 antigen escape.

The Company also announced that, in preparation for Phase 1 initiation, it had recently completed GMP production of FT596. In a single small-scale manufacturing campaign, the Company produced over 300 cryopreserved, infusion-ready doses of FT596 at a cost of approximately $2,500 per dose. The Company's iPSC product platform unites stem cell biology and precision genetic engineering to create renewable master engineered iPSC lines that can be repeatedly used to mass produce cancer-fighting immune cells, replacing the high production costs, weeks of manufacturing time, and complex manufacturing processes required for current-generation CAR T-cell immunotherapies with a lower-cost, easier-to-manufacture, well-characterized, off-the-shelf product that has the potential to reach many more patients.

FT596 is the third off-the-shelf, iPSC-derived NK cell product candidate from the Company's proprietary iPSC product platform cleared for clinical investigation by the FDA in the past twelve months. On Saturday, the Company announced that the first patient treated for acute myeloid leukemia in its Phase 1 clinical trial of FT516, an off-the-shelf, iPSC-derived NK cell cancer immunotherapy engineered to express hnCD16, showed no morphologic evidence of leukemia, chimerism of FT516 in the bone marrow, and hematopoietic recovery, including complete neutrophil recovery without growth factor support (>1,000 per L), after receiving three once-weekly doses of FT516 and IL-2 cytokine support.

About Fate Therapeutics' iPSC Product PlatformThe Company's proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company's first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company's platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics' iPSC product platform is supported by an intellectual property portfolio of over 250 issued patents and 150 pending patent applications.

About FT596FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 Fc receptor that has been modified to augment antibody-dependent cellular cytotoxicity by preventing CD16 down-regulation and enhancing CD16 binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. The FDA has allowed investigation of FT596 in an open-label Phase 1 clinical trial as a monotherapy, in combination with rituximab for the treatment of advanced B-cell lymphoma, and in combination with obinutuzumab for the treatment of chronic lymphocytic leukemia. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and CD16 receptors, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon dual receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a mixed cellular composition cytotoxicity assay comprised of CD19+ and CD19- tumor cells, FT596 combined with CD20-directed monoclonal antibody therapy effectively eliminated the heterogeneous population of tumor cells, a result that was not observed with single-antigen targeted CAR19 T cells.

About FT516FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 Fc receptor, which has been modified to prevent its down-regulation and enhance its binding to tumor-targeting antibodies. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma (clinicaltrials.gov ID number NCT04023071). CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. In addition, ADCC is dependent on NK cells maintaining active levels of CD16 expression, and the expression of CD16 on NK cells has been shown to undergo considerable down-regulation in cancer patients, which can significantly inhibit anti-tumor activity.

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Company's immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Company's immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Company's NK cell product candidates, including FT596 and FT516, its ongoing and planned clinical studies, and the expected clinical development plans for FT596 and FT516. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company may cease or delay planned development and clinical trials of any of its product candidates for a variety of reasons (including any delay in enrolling patients in current and planned clinical trials, requirements that may be imposed by regulatory authorities on the conduct of clinical trials or to support regulatory approval, difficulties in manufacturing or supplying the Company's product candidates for clinical testing, or the occurrence of any adverse events or other negative results that may be observed during development), the risk that results observed in preclinical studies of its product candidates, including FT596 and FT516, may not be replicated in ongoing or future clinical trials or studies, and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company's periodic filings with the Securities and Exchange Commission, including but not limited to the Company's most recently filed periodic report, and from time to time in the Company's press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

Fate Therapeutics Announces New Preclinical Data for FT596 Off-the-Shelf, iPSC-derived CAR NK Cell Cancer Immunotherapy - Benzinga

BREAKING: Baby body parts criminal trial to proceed against Daleiden with possible jail time – Lifesite

PETITION: Tell Attorney General Barr to PROSECUTE Planned Parenthood's alleged sale of baby body parts. Click here.

SAN FRANCISO, California, December 6, 2019 (LifeSiteNews) -- A San Francisco judge ruled today that pro-life investigators David Daleiden and Sandra Merritt will stand trial on nine felony counts of secretly recording conversations as part of their expos of Planned Parenthoods illegal harvesting and trafficking of aborted baby body parts.

In a ruling released today, Judge Christopher C. Hite of the San Francisco Superior Court dropped five counts against the Center for Medical Progress (CMP) pro-life investigators. He ruled, however, that there was sufficient evidence from the preliminary hearing to try Daleiden and Merritt on nine counts of breaking Californias anti-eavesdropping law during their undercover investigations.

Daleiden, 30, and Merritt, 64, could face jail time if convicted.

Thomas More Society, which represents Daleiden, tweeted:

Daleiden tweeted that the case is falling apart.

Former California Attorney General Kamala Harris concocted this bogus, biased prosecution with her Planned Parenthood backers against undercover video recording, and now their case is falling apart as the facts about Planned Parenthoods criminal organ trafficking are revealed in the courtroom, Daleiden said in a tweeted statement.

The remaining charges under the California video recording lawthe first and only time it has ever been used against undercover news gathererswill fall for the same reasons that five charges were dismissed today: these were public conversations easily overheard by third parties. The real criminals are the Planned Parenthood leadership who sold fetal-body parts from late-term abortions and weaponized the justice system to try to cover it up.

Daleiden and Merritt must now appear at California's Superior Court for instruction and arraignment on January 30.

Daleiden, Merritt and others secretly recorded gatherings of abortionists and organ harvesting companies, and CMP groundbreaking undercover videos released in July 2015 showed Planned Parenthood executives callously discussing how to dismember babies to procure intact organs and haggling over fees of aborted baby parts. The videos shocked the country and led to congressional and senate investigations into Planned Parenthood.

The abortion giant retaliated by suing the pro-life investigators.

A jury ruled November 15 that Daleiden, Merritt, Albin Rhomberg, and Troy Newman of Operation Rescue must pay Planned Parenthood $2.3 million in compensatory and punitive damages and lawyers fees for secretly recording Planned Parenthood and National Abortion Federation conferences in 2014 and 2015.

The pro-lifers are appealing the civil ruling.

Live Actions Lila Rose called Judge Hite's ruling today on the criminal prosecution an abuse of power.

Today's ruling proves unfounded and outrageous charges against two pro-life journalists who exposed the harvesting and trafficking of innocent babies. This is a gross abuse of power and a violation of the First Amendment, she wrote on Twitter.

Animal activist groups went undercover at a duck farm & former CA AG @KamalaHarris used their expose to try to ban foie gras. But when pro-life reporters exposed @PPFA execs haggling over baby parts, the reporters were prosecuted & the abortionists protected, she added in another Tweet.

Harris initiated the investigation of Daleiden and Merritt in 2016, and current Democrat Attorney General Xavier Beccera announced the charges at a press conference in March 2017.

Testimony and evidence presented at the preliminary hearing in September exposed this completely bogus, sham, politically motivated case for the farce that it is, Daleiden told LifeSiteNews in an earlier interview.

Documents from the case now on public record show Harris had an in-person meeting at the attorney generals meeting in Los Angeles with no less than six top-level Planned Parenthood of California executives, he said.

Daleiden added that the meeting took place a couple of weeks before Harris ordered Department of Justice agents to raid his Orange County apartment in April 2016 and seize all his recording materials, including unpublished source documents of his undercover investigation.

We have the minutes in an email from the meeting that Kamala had with the Planned Parenthood leadership, and in that meeting they discussed both Planned Parenthoods political agenda in the state of California, and they also discussed the attorney generals investigation of me and of CMP, Daleiden said.

PETITION: Tell Attorney General Barr to PROSECUTE Planned Parenthood's alleged sale of baby body parts. Click here.

Daleiden and Merritt are claiming a Section 633.5 defense that allows covert recording of confidential communications when done to collect evidence of violent crimes.

Defense is also arguing that the law does not consider confidential any conversation that can reasonably be expected to be overheard.

The two-week preliminary hearing also saw high-level Planned Parenthood abortionists along with the CEO of baby parts harvesting company StemExpress dodging questions on their gruesome business under cross-examination by pro-life defense lawyers.

It was the venue for Daleidens first-ever public testimony about why he embarked on a 30-month undercover sting operation into Planned Parenthood trafficking in aborted baby parts and how he penetrated the networks of those involved in the grisly and illegal business.

It included a cross-examination of investigating agent for the Department of Justice Brian Cardwell that showed he did next to nothing to find out if those accusing Daleiden and Merritt of illegally taping them were telling the truth or understood confidentiality as defined in the law.

It featured defense testimony by one of the United States longest-practicing abortionists Dr. Forrest Smith. He testified that it is almost certain that some of the abortionists featured in the undercover videos deliberately altered abortion procedures in a way that both led to the birth of living babies with beating hearts and put women at risk. The goal in such abortions would be to obtain fresher, more intact organs.

It also included testimony by stem cell expert Dr. Theresa Deisher that the human fetal hearts used in a 2012 Stanford University study and supplied by StemExpress had to be harvested while the babies were still alive.

The really shocking and troubling and clarifying truth that was exposed in the preliminary hearing is that its very, very clear that the only crimes that were committed in the course of the undercover videotaping that Center for Medical Progress did were the crimes committed by the Planned Parenthood abortion doctors, and by the StemExpress body parts harvesters who were forced to testify under oath these past two weeks, Daleiden told LifeSiteNews at that time.

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BREAKING: Baby body parts criminal trial to proceed against Daleiden with possible jail time - Lifesite

Jasper Therapeutics launches out of Stanford with new approach to stem cell treatment – Endpoints News

The first girl in the trial came in with chronic diarrhea and the immune system of an untreated HIV patient. Born with a rare genetic disease that impeded her ability to make B and T cells, she had once been given a stem cell transplant but it didnt take. Back in the hospital, she was injected with a new experimental antibody and then given a new stem cell transplant. Soon, she gained weight. The diarrhea stopped.

She has normal T cells now, Judith Shizuru, the Stanford scientist who pioneered the antibody, told Endpoints News. Shes in school.

Its the kind of medical story to launch a biotech around, and thats what Shizuruis doing. Today, her company Jasper Therapeutics is emerging out of stealth-mode with $35 million in Series A funding led by Abingworth and Qiming, a molecule from Amgen, and a Phase I trial set for its first readout on Monday at ASH.

Jasper is broadly aimed at making stem cell transplants safer, more accessible and more effective by using antibodies as conditioning agents. Theseagents clear out bone marrow to make room for the new stem cells to graft onto the body.

Their Phase I uses a naked antibody called JSP191 to help patients with severe combined autoimmune deficiency receive stem cell transplants the only possible cure for the life-threatening disease but such transplants are used in a wide variety of conditions and Jasper has broader aims. Those include other autoimmune diseases, acute myeloid leukemia and cell-directed gene therapy.

Theres a significant amount of progress being made in gene therapy, interim CEO William Lis told Endpoints, but no progress being made in a conditioning agent that will help graft gene therapy.

Shizuru path to the new antibody was long and fortuitous. In 1987, Arl Arzst, the legendary ad executive and president of Proctor and Gamble international flew in on a recruiting trip for Stanford business students. There he visited Shizuru, a young biologyPhD candidate, because he knew her roommate. Arzsts daughter had diabetes and as Shizuru explained the work she was doing on pancreatic islet cell transplants, he told her to come to Europe.

Shizuru had never been to Europe, but there Arszt introduced her to Ken Farber and the other founders of the Juvenile Diabetes Foundation (now the JDRF). The founders struck a years-long correspondence and encouraged Shizuru to go to medical school, where she decided that if scientists were ever going to develop transplants that didnt trigger an immune response, it would be through stem cell work. She continued her work at the Irv Weissman Stanford regenerative lab, where eventually a graduate student made a discovery that piqued her interest.

To put new stem cells in, you have to get the old stem cells out. Thats not always easy. The cells sit inthese pockets in the bone marrow, and theyre pretty comfortable there. Doctors have to force them out, often using chemotherapy or radiation, which damage DNA and cause severe side effects. The costs sometimes outweigh the benefits.

There are diseases were not treating because its too dangerous, Shizuru said. And the kids were treating, theyre so, so fragile.

The grad student had shown in mice that antibodies could be used to deplete the stem cells and potentially eliminate the need for chemotherapy or radiation. Shizuru and her team began looking to see if anyone had developed a human version of the antibody, CD117. It turned out Amgen had already developed a version of this antibody for a different use. It also turned out she had a former postdoc and a former advisor who worked there. They began a collaboration.

We set out to cross the valley of death, Shizuru said, using an industry slang term for the jump from animal models to human uses.

After making a variety of tweaks to the treatment, they published a paper inScience Translational Medicine in 2016showing the antibodies created a 10,000 fold reduction in the number of stem cells in mice.

The same year, they began a clinical trial on 90 SCID patients. These patients had received stem cell transplants when they were very young but hadnt been given chemo or radiation for fear the side effects would be too severe. The original transplants boosted their numberof immune cells, but without chemo or radiation, the stem cells dont graft into those pockets and the body wont continue producing T cells. Without those, they are extraordinarily prone to infection. Many pass away before age 2.

The hope is that the antibodies allowed the stem cells to graft, and the preliminary answer to that question will be out on Monday. For the first girl in the trial, life has improved but questions about how long her body will make immune cells remain. Still, for that girl and others, Shizuru is confident.

We see there is stem cell engraftment, Shurizi said. They are actually making new T cells.

See the rest here:
Jasper Therapeutics launches out of Stanford with new approach to stem cell treatment - Endpoints News

MaaT Pharma Announces the Presentation of Positive Data with Its Lead Microbiome Biotherapeutic in Intestinal-Predominant Acute…

MaaT Pharmas full-ecosystem microbiota biotherapeutic provided positive impact with satisfactory safety profile in eight patients with advanced stages of GI aGvHD

MaaT Pharma announced today that leading hemato-oncological experts presented clinical data on the compassionate use of MaaT Pharmas lead full-ecosystem microbiome restoration biotherapeutic, MaaT013. The data included eight patients that developed gastrointestinal-predominant, acute Graft-versus-Host-Disease (GI aGvHD) after receiving an allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) to treat their hematologic malignancies. All patients were positively impacted by the MaaT013 treatment, with three patients achieving complete response. GvHD, a condition where the transplant donors immune cells attack the patients tissues, is one of the most serious complications of allo-HSCT, and its acute GI form is fatal in most cases. MaaT013 features a consistently high diversity and richness of microbial species in their natural environment. It aims to restore the symbiotic relationship between microbes in the gut and the immune system of the patient to correct the responsiveness and tolerance (homeostasis) of immune functions and thereby contain GI GvHD. The results were presented in a poster presentation on December 7, 2019 during the 61st American Society of Hematology (ASH) Annual Meeting and Exposition held in Orlando, Florida.

"The GI aGvHD patients who were treated with MaaT013 had a very poor prognosis with no other therapeutic options. The results following MaaT013 administration showed a positive impact on all patients," commented Professor Mohamad Mohty, MD, PhD, Head of the Hematology and Cellular Therapy Department at Sorbonne University, Saint Antoine Hospital in Paris. "The most impressive results were seen in those patients who achieved a complete response and who were able to taper and stop using steroids and other immunosuppressants without relapse of gastrointestinal symptoms."

In the presented evaluation, eight patients with a median age of 67 were treated for classical aGvHD, late-onset aGvHD or aGvHD with overlap syndrome that were either steroid-resistant or steroid-dependent following stem cell transplantation. These patients had previously been treated with and failed up to five lines of systemic therapy for aGvHD. Each patient received at least one and up to three doses of MaaT013 and treatment response was evaluated seven days after each administration and on day 28 after the first dose. Based on the best response to the treatment, all eight patients experienced at least a partial response with three patients achieving complete response, two patients with very good partial response and three patients with partial response. Overall, the data demonstrated that reintroduction of a full-ecosystem microbiota provided therapeutic effect and was tolerated in a satisfactory manner in these patients.

Herv Affagard, Co-founder and CEO of MaaT Pharma added, "We provided our cGMP-manufactured lead biologic drug, MaaT013, to hospitals as part of a compassionate use program to give GI GvHD patients a therapeutic option where there are no other available treatments after steroids and additional lines of treatment. These findings indicate that reestablishing the gut microbiome improved outcomes in these patients."

Moreover, MaaT Pharma is currently conducting the HERACLES Phase II clinical trial (NCT03359980) to evaluate the safety and efficacy of MaaT013 in steroid-refractory, GI aGvHD patients, with more than half of the patients enrolled.

To date, a total of 46 patients with GI GvHD have been treated with MaaT013, including patients under compassionate use and patients enrolled in the Phase II clinical trial. MaaT Pharma is actively developing an oral formulation of MaaT013 (a capsule, MaaT033) to provide easier administration for patients while delivering a similar effect of regenerating the microbial ecosystem with the goal of restoring immune homeostasis in the gut.

The poster can be viewed on the companys website under "News".


The HERACLES study is a multi-center, single-arm, open-label study, enrolling 32 patients to evaluate the efficacy and safety of MaaT Pharmas lead microbiome restoration drug candidate, MaaT013, in steroid-resistant, gastrointestinal-predominant aGvHD patients. Acute GvHD is a serious, often fatal syndrome typically involving the gut, skin, and liver. Treatments up to now focused largely on suppressing the immune reaction that is induced by the donor cells derived from the hematopoietic stem cell graft reacting against the host. These strategies have remained clinically unsuccessful in most cases, with mortality rates around 80% after twelve months in steroid-resistant cases. Patients with hematological malignancies receive multiple courses of chemotherapy, antibiotics, and ultimately conditioning before HSCT, which are known to severely impact the gut microbial composition.

Story continues

About MaaT013

MaaT013 is the first full-ecosystem, off-the-shelf, reproducible, enema formulation manufactured using MaaT Pharmas integrated Microbiome Restoration Biotherapeutic (MMRB) platform. The product has a stability of up to 24 months and is characterized by a high diversity and consistent richness of microbial species derived from pooled healthy donors and manufactured at the companys centralized European cGMP production facility. MaaT013 has been granted Orphan Drug Designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and is already being administered in compassionate use.

About MaaT Pharma

MaaT Pharma, a clinical stage company, has established the most complete approach to restoring patient-microbiome symbiosis to improve survival outcomes in life-threatening diseases. Committed to treating blood cancers and Graft-versus-Host-Disease, a serious complication of allogeneic stem cell transplantation, MaaT Pharma has already achieved proof of concept in acute myeloid leukemia patients. Supporting the further expansion of our pipeline into improving outcomes of immunotherapy in solid tumors, we have built a powerful discovery and analysis platform, GutPrint, to evaluate drug candidates, determine novel disease targets and identify biomarkers for microbiome-related conditions. Our biotherapeutics are produced under the strictest cGMP manufacturing and quality control process to safely deliver the full diversity and functionality of the microbiome. MaaT Pharma benefits from the commitment of world-leading scientists and established relationships with regulators to spearhead microbiome treatment integration into clinical practice.

View source version on businesswire.com: https://www.businesswire.com/news/home/20191207005042/en/


For MaaT Pharma Herv Affagard, CEOPhone: +33 4 2829 1400E-Mail: haffagard@maat-pharma.com

Media Requests for MaaT Pharma Dr. Stephanie May or Dr. Jacob VergheseTrophic CommunicationsPhone: +49 89 23 88 77 30 or +49 171 185 56 82E-Mail: may@trophic.eu or verghese@trophic.eu

MaaT Pharma Announces the Presentation of Positive Data with Its Lead Microbiome Biotherapeutic in Intestinal-Predominant Acute...

Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers – GlobeNewswire

AUTO1 shows 87% MRD negative complete response in adult patients with r/r ALL, with no severe cytokine release syndrome

Data presented at 61st American Society of Hematology Annual Meeting form basis for advancement of AUTO1 into pivotal clinical trial in adult ALL

Investor call to be held December 9 at 8:30 am ET / 1:30 pm GMT to review data

LONDON, Dec. 07, 2019 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc(Nasdaq: AUTL) announced today new data highlighting progress on its next-generation programmed T cell therapies to treat patients with acute lymphoblastic leukemia (ALL) and adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data were presented in oral presentations at the 61stAmerican Society of Hematology(ASH) Annual Meeting and Exposition inOrlando, FL. Additional data on pediatric patients with ALL will be presented on December 8.

The data on AUTO1 presented at this years ASH meeting demonstrate the favorable safety profile and high level of clinical activity of AUTO1 in both adults and pediatric patients with ALL, and we look forward to initiation of the pivotal program in adult ALL in the first half of 2020, said Dr. Christian Itin, chairman and chief executive officer of Autolus.

Acute Lymphoblastic Leukemia Data Presented

Title: AUTO1 A novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL (Abstract # 226)

Updated results for ALLCAR19, the Phase 1 trial evaluating AUTO1 in adults with recurrent/refractory ALL, were presented by Dr. Claire Roddie MB, PhD, FRCPath, honorary senior lecturer,Cancer Institute, University College London (UCL), in an oral presentation. The trial is designed to assess the primary endpoints of safety ( Grade 3 toxicity) and feasibility of product generation, as well as other secondary endpoints, including efficacy. The trial enrolled patients with a high tumor burden (44% had 50% BM blasts), who were considered high-risk for experiencing cytokine release syndrome (CRS). Product was manufactured for 19 patients; product for 13 of those patients was manufactured using a semi-automated closed process, which will be used for commercial supply.

As of the data cut-off date of November 25, 16 patients had received at least one dose of AUTO1. AUTO1 was well tolerated, with no patients experiencing Grade 3 CRS, and 3 of 16 patients (19%), who had high leukemia burden, experiencing Grade 3 neurotoxicity that resolved swiftly with steroids.

Of 15 patients evaluable for efficacy, 13 (87%) achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. CD19-negative relapse occurred in 22% (2 of 15) patients. In the patients dosed with AUTO1 manufactured in the closed process, 9 of 9 (100%) achieved MRD negative CR at 1 month and 6 months event free survival, and overall survival in this cohort was 100%.

Adult ALL patients, who face a median survival of less than one year after their ALL recurs or relapses, have a significant need for a CAR T cell therapy that is highly active, safe and is a standalone therapy not requiring a stem cell transplant, said Dr. Hagop M. Kantarjian, Chair of the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

The novel CD 19 CAR-T therapy, AUTO1, is potentially transformative as a standalone curative option for patients with r/r ALL, especially in adults, given its favorable safety profile, said Dr. Max Topp associate professor of Internal Medicine, Hematology and Oncology at the University of Wuerzburg.

Title: Therapy of pediatric B-ALL with a lower affinity CD19 CAR leads to enhanced expansion and prolonged CAR T cell persistence in patients with low bone marrow tumor burden, and is associated with a favorable toxicity profile (Abstract # 225)

Dr. Sara Ghorashian, honorary senior lecturer, Great Ormond Street Institute of Child Health, University College London, presented updated data from the phase 1 CARPALL study of AUTO1 in pediatric ALL patients with low bone marrow tumor burden. The trial is intended to assess the primary endpoints of safety and proportion of patients in molecular complete remission at 1 month. The study recruited a total of 25 patients and stratified them into 2 cohorts. Fourteen patients were treated in cohort 1, which utilized a manual manufacturing process; product was unable to be generated in 3 patients. Median follow-up was 27 months in cohort 1. Seven patients were treated in cohort 2, which utilized the semi-automated closed manufacturing process, which will be used for commercial supply. The aim of cohort 2 was to demonstrate feasibility of manufacture at scale. Product was generated for 100% of patients. Median follow-up was 7 months in cohort 2.

AUTO1 was well-tolerated overall, with no patients experiencing Grade 3 CRS and 1 of 21 (5%) experiencing Grade 4 neurotoxicity, which was considered unrelated to CAR T therapy.

Nineteen of 21 treated patients (90%) achieved molecular complete remission at 1 month post infusion. Consistent with pre-clinical data, CAR T cell expansion was excellent and detectable by flow in a number of patients up to 36 months. Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months. In cohort 2, 100% of patients achieved molecular complete remission at 1 month post infusion.

In the 14 patients in cohort 1, the overall survival at 6 months was 86% and at 12 months was 71%; event free survival (EFS) at 6 months was 71% and at 12 months was 54%. The patients in cohort 2 are not yet evaluable for these parameters. Overall, nine patients relapsed; 5 of 8 evaluable relapses were due to loss of CD19 antigen on the tumor cells.

Title: Clonal dynamics of early responder and long-term surviving CAR-T cells in humans (Abstract # 52)

Dr. Luca Biasco, senior research associate at University College London, presented a detailed analysis of CAR T products, and insertion site analysis from the CARPALL phase 1 patients. This analysis revealed highly polyclonal engraftment, even at very late time-points. Dr. Biasco hypothesized that the propensity for high level polyclonal long-term engraftment was due to favorable phenotype of the CAR T product and the binding kinetic of the receptor.

Diffuse Large B-cell Lymphoma Data Presented

Title: Phase 1/2 study of AUTO3, the first bicistronic chimeric antigen receptor (CAR) targeting CD19 and CD22 followed by an anti-PD1 in patients with relapsed/refractory (r/r) Diffuse Large B Cell Lymphoma (DLBCL): Results of cohort 1 and 2 of the ALEXANDER study (Abstract # 246)

Dr. Kirit Ardeshna, consultant hematologist, Department of Hematology, University College London Hospital NHS Foundation Trust, presented updated data from the ALEXANDER Phase 1/2 study of AUTO3, the first bicistronic CAR T targeting CD19 and CD22 followed by an anti-PD1, in diffuse large B cell lymphoma (DLBCL). 16 patients were treated, and fourteen patients were evaluable at one month. AUTO3 was well-tolerated, with no patients experiencing Grade 3 CRS with primary treatment, and 1 of 14 experiencing Grade 3 neurotoxicity that resolved swiftly with steroids. Five of 14 had a complete response, with 4 of 5 complete responses ongoing, the longest at 18 months.

DLBCL is an aggressive and rapidly progressing cancer, and early response is critical to ensuring positive outcomes for these patients. These early data show the promise of AUTO3 in DLBCL, and we expect to advance AUTO3 to a decision point in relapsed/refractory DLBCL by the middle of next year, said Dr. Christian Itin, chairman and chief executive officer of Autolus. In addition, we look forward to presenting the data from the AMELIA trial of AUTO3 in pediatric ALL during poster sessions on Sunday, December 8, 6:00 8:00 PM ET.

Investor call to review data on Monday, December 9

Autolus management will host an investor conference call on Monday, December 9, at 8:30 a.m. EDT/ 1:30pm GMT, to review the data presented at ASH.

To listen to the webcast and view the accompanying slide presentation, please go to:https://www.autolus.com/investor-relations/news-and-events/events.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 9796038. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 9796038.

About AUTO1

AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety - while maintaining similar levels of efficacy - compared to current CD19 CAR T cell therapies.Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells' abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights fromUCL Business plc(UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL.

About AUTO3

AUTO3 is a programmed T cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that have each been independently optimized for single target activity. By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies. AUTO3 is currently being tested in pediatric ALL in the AMELIA clinical trial and in diffuse large B cell lymphoma in the ALEXANDER clinical trial.

AboutAutolus Therapeutics plc

Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit http://www.autolus.com.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to, statements regarding Autolus financial condition and results of operations, as well as statements regarding the anticipated development of Autolus product candidates, including its intentions regarding the timing for providing further updates on the development of its product candidates, and the sufficiency of its cash resources. Any forward-looking statements are based on management's current views and assumptions and involve risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section titled "Risk Factors" in Autolus' Annual Report on Form 20-F filed on November 23, 2018 as well as discussions of potential risks, uncertainties, and other important factors in Autolus' future filings with the Securities and Exchange Commission from time to time. All information in this press release is as of the date of the release, and the company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law.

Investor and media contact: Silvia TaylorVice President, Corporate Affairs and Communications Autolus+1-240-801-3850s.taylor@autolus.com

UK:Julia Wilson+44 (0) 7818 430877j.wilson@autolus.com

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Autolus Therapeutics Announces New Data Showcasing Clinical Progress of Programmed T Cell Therapy Pipeline in Blood Cancers - GlobeNewswire

Sickle Cell Anemia Patient Becomes First Person in the US to Have Her Genes Edited With CRISPR – Interesting Engineering

Last week, a woman namedVictoria Gray became the first person in the U.S. to have her cells edited with CRISPR. The41-year-old patient was sufferingfromsickle cell anemia.


The condition, caused by a genetic mutation that messes with the shape of red blood cells, causes havoc on patients, and to make things even worse, the options for treatment are very limited and ineffective. The only current treatment for sickle cell anemia patients is a donor transplant that works for just 10% of patients, but all that is about to change.

It was clear that analternative, much more effectivesolutionwas desperately needed. After much consideration, doctors believed that editing cells extracted from a patient's own bone marrow could restore effective red blood cell creation, and this is exactly the operation they attempted on Gray.

The doctors used CRISPR to tweak Gray's bone marrow DNA to turn on a specific protein that would allow proper red blood cell generation. The operation makes Gray the first person in the U.S. to undergo a CRISPR editing procedure and the second globally.

The treatment comes from observations made back in the 1940s.In 1941 a pediatrician named Jane Watson noticed that babies with sickle cell didnt have symptoms until 6 months to 1 year of age, Vivien Sheehan, a hematologist at Baylor University told Popular Science.

The pediatrician also discovered that these infants produced fetal hemoglobin for much longer periods than healthy babies.Following Watson's observations, the research since then has indicated that increasing fetal hemoglobin could provide an effective treatment for the disease.

Now, CRISPR may just make that treatment viable. But before we get too excited, it should be noted that the strategy comes with several risks.

In order for the edited cells to be inserted back into the patients bone marrow, other stem cells need to be deactivated. Otherwise, there is the chance the unedited stem cells may continue to produce sickled red blood cells very fast, outpacing the edited cells' production of healthy cells.

Now researchers say they need to follow Gray's progress for at least 15 years to rule out any other potential dangers of the procedure. Still, for those 90% suffering with sickle cell anemia that don't respond well to current treatment, the procedure, if successful, would offer the much-needed lifeline they've been hoping for.

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Sickle Cell Anemia Patient Becomes First Person in the US to Have Her Genes Edited With CRISPR - Interesting Engineering

Ask the Doc! Check-ups and Stem Cell – Clay Co N.C. – Fetchyournews.com

Ask the Doc! Check-ups and Stem Cell Health December 6, 2019 , by Destyne Riblett

Dr. William Whaley answers your questions about getting family members to go for check-ups and one family asking about stem cells in cancer treatment.

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Teen diagnosed with cancer again just months after being told he beat disease – Mirror Online

A teenage boy has been diagnosed with an aggressive cancer again just four months after a doctor told him he had beaten the devastating disease.

There is just a 10 per cent chance that chemotherapy will work this time for 17-year-old Jacob Fradgley, who is "wasting away", his heartbroken mum said.

The teen, from Skegby in Nottinghamshire, originally found out that he had metastatic Ewing sarcoma, a rare form of bone cancer, when he was just 15 in May 2018.

After a "whirlwind" year of treatment, including 19 rounds of chemotherapy and 56 sessions of radiation therapy, Jacob was classed as cancer free in July, his mum, Sammy Fradgley, 34, told NottinghamshireLive.

But they were given the heartbreaking news that his cancer had returned after his mum found a lump on his head just weeks before Christmas.

Jacob was diagnosed with a relapse of metatistic ewing sarcoma, which affects bones and bone tissue.

Only 30 children a year are diagnosed in the UK.

Miss Fradgley has launched a campaign to fulfil some of her son's wishes - including meeting ex-soldier Ant Middleton SAS: Who Dares Wins - after doctors told her that if there was anything he wanted to do he should "do it now".

After his mum found the lump, Jacob was taken to Queen's Medical Centre in Nottingham for a CT scan.

He underwent surgery to remove the tumour in his head a week later.

Doctors then found more tumours in his head, hip and knees.

Miss Fradgley, a senior carer, said: "It took me two weeks to accept it.

"There's not a lot out there to treat a relapse, and we're just getting further away from solutions.

"There's around a 10 per cent chance the chemotherapy will work this time.

"You never think it's going to come back but I've just got to support him now."

Jacob had his final round of radiation therapy in January and his last round of chemo on New Year's Eve.

In the following months he took medication to prevent the cancer returning.

His mum said: "He was able to go to his prom, he was going to cadets and studying Public Services at Vision West Notts College.

"But three weeks ago I was touching his hair, and felt the lump. It all just happened so quick.

"Now its more or less the same thing. It's so aggressive and is known for coming back."

She added: "It has upset him, that he has to go through it all again.

"He has to have six rounds of chemotherapy and the doctors also want to harvest stem cells. If the chemo works, he may be able to go for stem cell treatment."

Jacob's consultant has told her that if there was something he wanted to do he should "do it now".

She has launched a JustGiving campaign to raise enough money so Jacob can create memories with his six-year-old sister Leah.

It has raised more than 2,300 so far.

Miss Fradgley said: "I just don't want to say no. I want to give him everything he wants.

"It's so hard to just watch him wasting away in front of me, but I am trying to do everything I can for him.

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"He does still smile, but I am also there when he gets upset.

"His biggest aspiration is to drive a tank, meet Ant Middleton - anything to do with the army.

"His favourite colour is red so I have also started a 'Going Red for Jacob' campaign and I plan to make red bands with 'Team Fradgley' so everyone can support him and donate."

Barbera White, founder of the When You Wish Upon a Star charity, which is supporting the family, said: "I just wanted mum to know if there's anything we can do, we will try.

"I am trying to arrange a wish for him and I am currently working on something that I know he wants.

"Even after 30 years of the charity, I keep in touch with the families I meet, and we all want to help create some memories for Jacob."

Last December, the charity gave Jacob, his mum and his sister a trip to Lapland as he battled cancer.

At the time, he was looking forward to spending Christmas out of hospital and said the Lapland trip was a chance to "be together like a normal family".

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Teen diagnosed with cancer again just months after being told he beat disease - Mirror Online