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DUARTE, Calif. & TOA BAJA, Puerto Rico--(BUSINESS WIRE)--City of Hope, a world-renowned cancer research and treatment organization, and CytoImmune Therapeutics, a clinical-stage immunotherapy company that is developing a novel class of natural killer (NK) cell-based cancer therapies, today announced a study published in the high-impact journal Gastroenterology that demonstrates off-the-shelf anti-prostate stem cell antigen (PSCA) chimeric antigen receptor (CAR) NK cells significantly suppressed pancreatic cancer in vitro and in vivo using a method known as freeze-thaw.

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The therapy PSCA CAR_s15 NK cells, also known as CYTO NK-203 persisted more than 90 days after infusion and significantly prolonged the survival of mice with pancreatic cancer, showing that the freeze-thaw method works. For the study, PSCA CAR_s15 NK cells were produced and then frozen. The cells were then thawed and used in preclinical studies at City of Hope.

Our patients need additional ways to attack their pancreatic cancer. The work presented by City of Hopes team is distinctive and promising for two reasons: First of all, it is based on a precision medicine approach that is a special target in the patient's pancreatic cancer PSCA. Secondly, it is an immunologic approach, using human natural killer cells, which are specifically engineered to attack the patient's cancer. These findings should be accelerated to a clinical trial as rapidly as possible, said Daniel D. Von Hoff, M.D., a distinguished professor in the Molecular Medicine Division of the Translational Genomics Research Institute (TGen), an affiliate of City of Hope. He also is senior consultant-clinical investigator at City of Hope and is one of the nations leading authorities on the treatment and care of pancreatic cancer patients.

City of Hope is committed to finding more effective and innovative treatments for difficult-to-treat solid cancers, and pancreatic cancer is clearly one of them, said Saul Priceman, Ph.D., assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope and a study author. These new PSCA CAR_s15 NK cell preclinical studies provide tremendous support for the anticipated upcoming clinical trials to evaluate efficacy and safety of this novel CAR-engineered NK cell therapy in patients with pancreatic cancer, which is a promising expansion of our existing clinical programs that target PSCA in solid cancers using CAR-engineered T cell therapy.

Pancreatic cancer is the third leading cause of cancer-related death in the United States with a five-year survival rate of approximately 10%. The cancer is typically detected when it is at a late stage and incurable. Chemotherapy or other therapies provide modest benefit. Therefore, the development of new therapies for pancreatic cancer is crucial. The therapy can also be used for other PSCA+ cancers, such as stomach and prostate.

NK cell technology works by using natural killer cells from a patient or donor. NK cells are then engineered so they express a receptor a CAR that is specific for a protein expressed by cancerous cells, along with the secretion of IL-15, which sustains the survival of the NK cells.

Christina Coughlin, M.D., CEO of CytoImmune Therapeutics, said, "We are excited to share this data on our CAR NK candidate for pancreatic cancer. This foundational data supports robust anti-tumor activity with CYTO NK-203, making us confident our innovative and off-the-shelf NK cell therapy approach has the potential to deliver more accessible, safe and effective cell-based treatment options to cancer patients. We are encouraged by these findings and look forward to continuing our work with City of Hope in order to move this initiative to the clinic.

This immunotherapy is revolutionizing the treatment of some blood cancers; however, its use in the treatment of solid tumors has been limited, in part because most of the proteins currently used to target CAR cells to solid tumors are present in low levels on other normal tissues, leading to toxic side effects.

Based on research by Michael Caligiuri, M.D., president of City of Hope National Medical Center and the Deana and Steve Campbell Physician-in-Chief Distinguished Chair, and Jianhua Yu, Ph.D., professor and director of the Natural Killer Cell Biology Research Program, who have nearly 55 years of collective laboratory investigation of NK cells, CytoImmune is developing an NK cell platform designed to overcome the limitations and challenges of current technologies for engineering NK cells. The platform is designed to generate an abundant supply of CAR NK cells from a single umbilical cord donor, engineered with the CAR for effective recognition of tumor targets, and secreting IL-15 to improve the persistence of CAR NK cells for sustained activity in the body. The process enables scientists to freeze, transport and store engineered CAR NK cells for off-the-shelf use for the treatment of cancer.

The study titled Off-the-shelf PSCA-directed chimeric antigen receptor natural killer cell therapy to treat pancreatic cancer can be found here.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nations Best Hospitals in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. Translational Genomics Research Institute (TGen) became a part of City of Hope in 2016. AccessHopeTM, a subsidiary launched in 2019, serves employers and their health care partners by providing access to NCI-designated cancer center expertise. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

About CYTO NK 203

CYTO NK-203 is an off-the-shelf allogeneic CAR NK cell therapy derived from umbilical cord blood, expressing a CAR against prostate stem cell antigen and soluble IL-15 and engineered with proprietary features designed to improve the safety and efficacy of NK cells as a potential therapy.

About CytoImmune Therapeutics Inc.

Founded in 2017, CytoImmune Therapeutics is a clinical-stage biotechnology company, focused on developing an innovative and differentiated pipeline of NK cell therapies, using proprietary, robust and well characterized NK cell expansion and engineering technologies pioneered by Michael Caligiuri, M.D., and Jianhua Yu, Ph.D. The pipeline includes cytokine induced NK (CI-NK) for lung cancer, FLT3 CAR-NK for acute myeloid leukemia, PSCA CAR-NK cells for solid tumors and GPRC5D BiKE secreting BCMA CAR-NK cells for multiple myeloma. CytoImmunes lead product, CYTO-102 (CI-NK) cell therapy, aims to enter the clinic in combination with atezolizumab (anti-PD-L1 monoclonal antibody) for nonsmall cell lung cancer in 2022.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220118005366/en/

City of HopeLetisia Marquezlemarquez@coh.org626-476-7593

CytoImmuneWilliam Roselliniwill@cytoimmune.com

Source: City of Hope

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City of Hope and CytoImmune announce study demonstrating novel off-the-shelf chimeric antigen receptor (CAR) natural killer (NK) cell-based therapy...

This article was originally published here

Am J Transl Res. 2021 Dec 15;13(12):13261-13272. eCollection 2021.

ABSTRACT

Diabetic foot ulcers (DFUs) are a serious complication of diabetes and the main cause of nontraumatic lower limb amputations, resulting in a serious economic burden on society. The main causes of DFUs include peripheral neuropathy, foot deformity, chronic inflammation, and peripheral artery disease. There are many clinical approaches for the treatment of DFUs, but they are all aimed at addressing a single aetiological factor. Stem cells (SCs), which express many cytokines and a variety of nerve growth factors and modulate immunological function in the wound, may accelerate DFU healing by promoting angiogenesis, cell proliferation, and nerve growth and regulating the inflammatory response. However, the survival time of SCs without scaffold support in the wound is short. Multifunctional gel wound dressings play a critical role in skin wound healing due to their ability to maintain SC survival for a long time, provide moisture and prevent electrolyte and water loss in DFUs. Among the many methods for clinical treatment of DFUs, the most successful one is therapy with gel dressings loaded with SCs. To accelerate DFU healing, gel wound dressings loaded with SCs are needed to promote the survival and migration of SCs and increase wound contraction. This review summarizes the research advancements regarding multifunctional gel wound dressings and SCs in the treatment of DFU to demonstrate the effectiveness and safety of this combinational therapeutic strategy.

PMID:35035674 | PMC:PMC8748097

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The role of gel wound dressings loaded with stem cells in the treatment of diabetic foot ulcers - DocWire News

Researchers at Mayo Clinic's campus in Florida have conducted the world's first prospective, blinded and placebo-controlled clinical study to test the benefit of using bone marrow stem cells to reduce arthritic pain and disability in knees.

It is the first time that the belief that stem cells can provide substantial and possible regenerative relief in an ailing joint has been put to the test in such a rigorous fashion. The researchers say such testing is needed because there are at least 600 stem cell clinics in the U.S. offering one form of stem cell therapy or another to an estimated 100,000-plus patients, who pay thousands of dollars, out of pocket, for the treatment, which has not undergone demanding clinical study.

The findings in The American Journal of Sports Medicine represent another first patients not only had a dramatic improvement in the knee that received stem cells, but also in their other knee, which also had painful arthritis but received only a saline control injection. Each of the 25 patients enrolled in the study had two bad knees, but did not know which knee received the stem cells.

Given that the stem cell-treated knee was no better than the control-treated knee both were dramatically better than before the study began the researchers say the stem cells' effectiveness remains somewhat uninterpretable. They are only able to conclude the procedure is safe to undergo as an option for knee pain, but they cannot yet recommend it for routine arthritis care.

Our findings can be interrupted in ways that we now need to test one of which is that bone marrow stem cell injection in one ailing knee can relieve pain in both affected knees in a systemic or whole-body fashion, says the study's lead author, Shane A. Shapiro, M.D., a Mayo Clinic orthopedic physician.

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Mayo Clinic uses stem cell therapy to treat arthritis in ...

Introduction: The prevalence of erectile dysfunction (ED) is substantial and continues to rise. Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function. Stem cell therapy has been evaluated for erectile restoration in animal models. These cells have been derived from multiple tissues, have varied potential, and may function via local engraftment or paracrine signaling. Bone marrow-derived stem cells (BMSC) and adipose-derived stem cells (ASC) have both been used in these models with noteworthy effects.

Aim: Herein, we will review the pathophysiology of ED, animal models, current and novel stem-cell based therapeutics, clinical trials and areas for future research.

Methods: The relevant literature and contemporary data using keywords, "stem cells and erectile dysfunction" was reviewed.

Main outcome measure: Examination of evidence supporting the association between erectile dysfunction and adipose derived stem cells, bone marrow derived stem cells, placental stem cells, urine stem cells and stem cell therapy respectively.

Results: Placental-derived stem cells and urine-derived stem cells possess many similar properties as BMSC and ASC, but the methods of acquisition are favorable. Human clinical trials have already demonstrated successful use of stem cells for improvement of erectile function.

Conclusion: The future of stem cell research is constantly being evaluated, although, the evidence suggests a place for stem cells in erectile dysfunction therapeutics. Matz EL, Terlecki R, Zhang Y, et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2019;7:321-328.

Keywords: Erectile Dysfunction; Impotence; Regenerative Medicine; Stem Cell Therapy.

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Stem Cell Therapy for Erectile Dysfunction

Stem cell is considered a potential therapy for treating erectile dysfunction (ED), including diabetic mellitus erectile dysfunction (DMED), which was investigated in some preclinical studies. Several trials introduced stem cell into clinical practice, but divergences emerged.

To further investigate the therapeutic effects of stem cell on DMED in preclinical studies and investigate some possible factors that influence curative effects.

The literature research was conducted in Web of Science and PubMed to retrieve studies utilizing stem cell to treat DMED. Revman 5.3 was used to perform subgroup analysis of intracavernosal pressure/mean artery pressure (ICP/MAP) and structural changes. Publication bias was assessed with Egger's test, funnel plot, and sensitivity analysis by Stata 15.0.

The ICP/MAP and structural changes before and after stem cell treatment.

Of 2,115 studies retrieved, 23 studies are eligible. Plus 10 studies from a meta-analysis published in 2016, 33 studies were enrolled. Pooled analysis showed that stem cell ameliorates damaged ICP/MAP (WMD 0.26; 95% CI 0.230.29;P< .001) and structural changes induced by diabetes. Subgroup analysis indicated that adipose-derived mesenchymal stem cell (ADSC) may have better efficacy than bone marrow-derived mesenchymal stem cell (BMSC) (2= 4.21,P=.04; ADSC WMD 0.28, 95% CI [0.240.32] vs BMSC WMD 0.22 95% CI [0.170.26]). Transplantation type, diabetes type, and cell number make no difference to curative effects. Gene modification and therapy combination proved promising in improving the therapeutic effects of stem cell.

The evidence reminded that ADSC may be prior to BMSC in clinical trials and autotransplantation is probably not compulsory in the clinical practice of stem cell.

The study number and sample size are large enough. However, high degree of heterogeneity remains after subgroup analysis.

This meta-analysis suggests the efficacy of stem cell therapy for DMED and the possible superiority of ADSC over BMSC in erection restoration and structure renovation.

Yao C, Zhang X, Yu Z, et al., Effects of Stem Cell Therapy on Diabetic Mellitus Erectile Dysfunction: A Systematic Review and Meta-analysis. J Sex Med 2022;19:2136.

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Effects of Stem Cell Therapy on Diabetic Mellitus Erectile Dysfunction: A Systematic Review and Meta-analysis - Newswise

Abstract

Stem cell transplantation has been applied to treat spinal cord injury (SCI) in clinical trials for many years. However, the clinical efficacies of stem cell transplantation in SCI have been quite diverse. The purpose of our study was to systematically investigate the efficacy of stem cell transplantation in patients with SCI. The PubMed, Web of Science, Ovid-Medline, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang, and SinoMed databases were searched until October 27, 2020. Quantitative and qualitative data were analyzed by Review Manager 5.3 and R. Nine studies (n = 328) were included, and the overall risk of bias was moderate. The ASIA Impairment Scale (AIS) grading improvement rate was analyzed in favor of stem cell transplantation group [odds ratio (OR) = 6.06, 95% confidence interval (CI): 3.1611.62, P < 0.00001]. Urodynamic indices also showed improvement in bladder function. In subgroup analyses, the results indicated that in patients with complete (AIS A) SCI, with the application of cell numbers between n*(107 108 ), two cell types (i.e., bone marrowderived mesenchymal stem cells and bone marrow mononuclears), and treatment time of more than 6 months, stem cell transplantation was more beneficial for sensorimotor function (P < 0.05 for all groups). The risk of fever incidence in the stem cell transplantation group was 4.22 (95% CI: 1.710.22, P = 0.001), and principal component analysis (PCA) suggested it was more related to transplanted cell numbers. Thus, stem cell transplantation can promote functional recovery in SCI patients. Moreover, the type and quantity of transplanted stem cells and treatment time are important factors affecting the therapeutic effect of stem cell transplantation in SCI. Further studies are needed to evaluate the effects and elucidate the mechanisms of these factors on stem cell therapy in SCI.

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Evaluation of the Clinical Efficacy of Stem Cell Transplantation in the Treatment of Spinal Cord Injury: A Systematic Review and Meta-analysis -...

Innovative approaches in multiple myeloma that focus on cellular therapies offer hope to patients with multiple myeloma.

Current approaches for multiple myeloma are stratified by patient fitness and age. For patients who can tolerate them, 3- or 4-drug combinations, with or without an autologous stem cell transplant (ASCT), can result in a complete remission, ideally with no residual disease. For patients who are elderly or fragile, 2-drug or 3-drug regimens are the standard.

For the standard-risk patient, a regimen of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) plus a CD38 monoclonal antibody such as daratumumab (Darzalex) or isatuximab (Sarclisa) is the norm. As a whole, these combinatorial approaches are needed because multiple myeloma is a heterogenous disease whose optimal treatment takes advantage of multiple mechanisms of action. These regimens can result in first remissions that range from 4 to 5 years.

Although these outcomes are promising, there is still an unmet need for patients with relapsed or refractory disease. Innovative approaches in multiple myeloma that focus on cellular therapies offer hope to these patients.

In a presentation during the 39th Annual CFS Innovative Cancer Therapy for Tomorrow, Shambavi Richard, MD, an assistant professor in medicine, hematology, and medical oncology at The Mount Sinai Hospital in New York, New York, addressed the emerging therapeutic frontiers in multiple myeloma with a focus on chimeric antigen receptor (CAR) approaches and bispecific antibodies.1 Richard explored updated results from the KarMMa trial (NCT03361748), which enrolled 149 patients with relapsed/refractory multiple myeloma (RRMM) and who were previously exposed to immunomodulatory agents, proteasome inhibitors (PIs), and CD38 antibodies (mAbs) and reported poor outcomes. Evaluable patients received idecabtagene vicleucel (ide-cel; n = 128).2,3

At a median follow-up of 15.4 months, the objective response rate (ORR) was 73% and median progression-free survival (PFS) was 8.8 months for all treated patients (TABLE3 ). Investigators reported that at the highest targeted dose of 450 106 CAR T cells, the overall response rate (ORR) was 81%, the complete response (CR) rate was 39%, and the median PFS increased by 12.2 months with longer follow-up. In a subgroup analysis of difficult-to-treat patients, the ORR for patients with extramedullary disease was 70%; patients with high-tumor burden, 71%; and patients with R-ISS stage III disease, 48%.

Regarding safety, 97% of patients had cytopenia and 89% had grade 3/4 neutropenia; 52% experienced thrombocytopenia and 60% developed anemia. Cytokine release syndrome (CRS) had a median onset of 1 day, with a median duration of 5 days. CRS was seen in 84% of patients but grade 3/4 was observed in only 6% of patients. Neurologic toxicity was observed in 18% of patients and 4% were grade 3/4.

Updated results from the CARTITUDE-1 trial (NCT03548207)4 showed that ciltacabtagene autoleucel (cilta-cel) yielded early, deep, and durable responses in heavily pretreated patients with multiple myeloma, with a manageable safety profile at the recommended phase 2 dose.

In the study, 97 patients with a median of 6 prior lines received cilta-cel. The overall response rate per independent review committee (primary end point) was 97% (95% CI, 91%-99%), with 67% of patients achieving stringent CR (sCR). The median time to first response was 1 month (range, 1-9), and median time to CR or better was 2 months (range, 1-15). Responses deepened over time, and the median duration of response was not reached. Of 57 patients evaluable for minimal residual disease (MRD) assessment, 93% were MRD-negative at 10-5. The 12-month PFS and overall survival (OS) rates (95% CI) were 77% (66%-84%) and 89% (80%-94%), respectively; the median PFS was not reached.

In terms of adverse events, neutropenia was 94.8% grade 3/4, and 60.8% of patients had grade 3/4 anemia, said Richard. CRS was almost universal, with any-grade CRS seen in 94.8% of patients. This was a little different compared with ido-cel in terms of time of onset, which was 7 days with this product vs 1 day with the ido-cell product, she said. In both of these trials, early death within the first 2 to 3 months was 2% or less.

When comparing ide-cel to conventional treatment, according to findings presented by Shah et al,5 the investigators observed that ide-cel was associated with a significantly higher ORR compared with conventional treatment (OR, 5.11; 95% CI, 2.92-8.94; P < .001). Similarly, ide-cel significantly extended PFS (HR, 0.55; 95% CI, 0.42-0.73; P < .001) and OS (HR, 0.36; 95% CI, 0.24-0.54; P < .001) vs conventional treatment. Richard said this analysis aimed to compare efficacy outcomes observed with ide-cel treatment in KarMMa and conventional treatment in the Monoclonal Antibodies in Multiple Myeloma: Outcomes After Therapy Failure (MAMMOTH) study.6 Investigators analyzed outcomes of 275 patients with multiple myeloma with disease refractory to CD38 monoclonal antibodies at 14 academic centers.

Turning to the challenge of resistance to therapies in multiple myeloma, Richard noted that there are 3 main strategies in play: multiple myelomacell directed, T-cell directed; and CAR construct.

Possible strategies employed that use multiple myeloma celldirected treatments involve pooling CAR T products with different antigens; using dual CAR products that are constructed using 2 antigen specifi cities, such as B-cell maturation antigen (BCMA)/CD19; or taking a tandem CAR approach. Investigators also can focus on alternate antigens including SLAMF7, CD138, or integrin beta7.

Strategies that are T-cell directed can focus on those that are enriched for central or stem cell memory T cells or use combination approaches with checkpoint inhibitors or immunomodulatory imide drugs and cereblon E3 ligase modulators (CelMoD).

Efforts that tweak the CAR construct are also undergoing evaluation. These include FasTCAR, in which manufacturing takes 24 to 36 hours; next-generation CARs, which are armored CAR T cells that prevent T-cell exhaustion; CARs that use a safety switch to mitigate adverse effects; and allogeneic CARS.

Richard highlighted results from a study evaluating teclistamab, a bispecific antibody that binds to BCMA and CD3 to redirect T cells to attack multiple myeloma cells.

Findings from MajesTEC-1 (NCT03145181) demonstrated that the ORR in response-evaluable patients treated at the recommended phase 2 dose (n = 40) was 65% (95% CI, 48%-79%); 58% achieved a very good partial response or better.7 At the recommended phase 2 dose, the median duration of response was not reached. After 7.1 months median follow-up, 22 (85%) of 26 responders were alive and continuing treatment. During the 2021 American Society of Clinical Oncology Annual Meeting, Krishnan et al presented updated findings showing 58% of evaluable patients had achieved a very good partial response or better and 30% had achieved a CR or better; the median time to first confirmed response was 1.0 month (range, 0.2-3.1).8

Another bispecific antibody, talquetamab, has continued to show promising clinical activity in patients with RRMM. Updated findings from a phase 1 trial (NCT03399799)9 showed the ORR at the recommended phase 2 dose (RP2D) in response-evaluable patients (n = 24) was 63%, with 50% reaching very good partial response or better; 9/17 (53%) evaluable patients with triple-class refractory disease and 3/3 (100%) patients who were penta-refractory had a response. Median time to first confirmed response at the RP2D was 1.0 month (range, 0.2-3.8). Overall, responses were durable and deepened over time (median follow-up, 6.2 months [range, 2.7-9.7+] for responders at the RP2D).

When comparing CAR T-cell therapy to bispecific antibodies, Richard noted that patients undergo CAR T-cell therapy once with no further therapy indicated. Additionally, patients can enjoy a long chemotherapy holiday, whereas bispecific antibodies require more frequent doses. Toxicities are similar for the 2 approaches, although Richard said that CRS can be slightly more profound and at a somewhat higher grade with the CAR T-cell approach compared with that of bispecific antibodies.

In conclusion, Richard also noted that the costs associated with both these approaches will have an impact, especially in high up-front costs. Bispecific c antibodies, however, due to their chronic recurrent administration, may also come with a long-term financial burden.

REFERENCES:

1. Richard S. New therapeutic frontiers for RRMM: CAR T and bispecifi c antibodies. Presented at: 39th Annual CFS. Chemotherapy Foundation Symposium. Innovative Cancer Therapy for Tomorrow. November 3-5, 2021; New York, NY.

2. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850

3. Anderson LD, Munshi NC, Shah N, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: Updated KarMMa results. J Clin Oncol. 2021;39(suppl 15):8016-8016. doi: 10.1200/JCO.2021.39.15_suppl.8016

4. Usmani SZ, Berdeja JG, Madduri D, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy, in relapsed/refractory multiple myeloma: updated results from CARTITUDE-1. J Clin Oncol. 2021;39(suppl 15; abstr 8005). doi: 10.1200/JCO.2021.39.15_suppl.8005

5. Shah N, Ayers D, Davies FE, et al. A matching-adjusted indirect comparison of efficacy outcomes for idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy versus conventional care in triple-class-exposed relapsed and refractory multiple myeloma. Presented at: 62nd American Society of Hematology Meeting and Exposition, December 5-8, 2020. Abstract 1653. https://bit.ly/3nQb458

6. Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33(9):2266-2275. doi:10.1038/ s41375-019-0435-7

7. Usmani SZ, Garfall AL, van de Donk NWCJ, et al. Teclistamab, a B-cell maturation antigen CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021;398(10301):665- 674. doi:10.1016/S0140-6736(21)01338-6

8. Krishnan AY, Garfall Al, Mateos M-V, et al. J Clinical Oncol. 2021;39(suppl 15):8007-8007. doi: 10.1200/JCO.2021.39.15_suppl.8007

9. Berdeja JG, Krishnan AY, Oriol A, et al. Updated results of a phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM). J Clin Oncol. 2021;39(suppl 15):8008. doi: 10.1200/JCO.2021.39.15_suppl.8008

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Cellular Therapies Fill Unmet Needs in R/R Multiple Myeloma - Targeted Oncology

Some of the most anticipated presentations at the 63rd Annual American Society of Hematology (ASH) Meeting and Exposition involve phase 3 results for chimeric antigen receptor (CAR) T-cell therapy in second-line treatment.

In 2017, FDA approved the first chimeric antigen receptor (CAR) T-cell therapies, tisangenlecleucel (tisa-cel), sold as Kymriah, and axicabtagene cilocleucel (axi-cel), sold as Yescarta, for patients with B-cell lymphomas treated with at least 2 prior therapies.

Not long after the question arose: would patients have better responses if they received CAR T-cell therapy earlier?

Its a question that will get some answers during the 63rd Annual American Society of Hematology Meeting and Exposition, which takes place December 11-14 in Atlanta and online. Some of the most anticipated presentations at ASH involve phase 3 results for CAR T-cell therapy in second-line treatment, and there are also phase 2 results for axi-cel in the first-line setting coming Monday.

Given the cost of CAR T-cell therapy, which lists for $373,000 to $475,000, depending on the indication, the answer is important to payers, who want to know if these expensive processes are more likely to succeed if patients are treated when their immune systems are less depleted. CAR T-cell therapy works by harnessing the patients own immune system to fight cancer cells.

Theres also the issue of avoiding the cost of prior treatments. However, Peter Marks, MD, PhD, director of FDAs Center for Biologics Evaluation and Research,said during a keynote address in October that widespread use of CAR T-cell therapy at earlier stages might only come if the cost of these treatments came down significantly.

Second-line treatment in LBCL. Two presentations will address this, led by the primary analysis of ZUMA-7, the phase 3 randomized trial that examines the use of axi-cel vs second-line standard of care in relapsed/refractory large B-cell lymphoma (LBCL). Gilead Sciences, which sells axi-cel as Yescarta, announced in June that results showed axi-cel offered a 62% event-free survival benefit over chemotherapy and stem-cell transplant. Results will be presented in Sundays plenary session by Frederick Locke, MD, of Moffitt Cancer Center. Axi-cel is currently approved for LBCL or follicular lymphoma when patients have received at least 2 other therapies.

The race is already on for use of axi-cel in the first-line stage, with phase 2 results from ZUMA-12 to be presented by Sattva S. Neelapu, MD, of MD Anderson Cancer Center.

Getting a jump on ZUMA-7 will be a Saturday morning presentation on interim findings from the phase 3 TRANSFORM study involving lisocabtagene maraleucel (liso-cel), which was approved earlier this year for patients with certain types of LBCL who have received at least 2 treatments. Sold as Breyanzi, liso-cel has a different manufacturing process that investigators say results in less toxicity than earlier CAR T-cell therapies. Officials from Bristol Myers Squibb also announced a significant benefit based on early results; the prespecified interim analysis to be presented at ASH shows event-free survival of 10.1 months, while overall survival data are immature.

Results for tisa-cel in the second-line setting will be presented in the late-breaking session Tuesday, but Novartis announced in August that the BELINDA study did not meet its end point.

Biomarkers and CAR T-cell therapy. Payers will be interested in the effort by 12 academic institutions to track molecular features for 121 patients with diffuse LBCL and assess which biomarkers had effects on clinical outcomes after the patients were later treated with tisa-cel or axi-cel. This study promises to identify possible targetable pathways to bring better responses to CAR T-cell therapy and identify which patients will have the best outcomes.

MCL in real-world settings. FDA approved brexucabtagene autoleucel (brexu-cel) in mantle cell lymphoma (MCL) in July 2020, based on results from the ZUMA-2 trial that showed a 90% objective response rate (ORR) and a 67% complete response rate (CR). A study to be presented by the US Lymphoma Consortium leverages the use of real-world data to show that patients with MCL who fell outside the ZUMA-2 criteria have reported high safety and efficacy rates when treated with brexu-cel.

Beyond R-CHOP. For patients with previously untreated LBCL, there will still be choices beyond CAR T-cell therapy. Results from Tuesday mornings late-breaking abstracts will start with the phase 3 POLARIX study, which examines the use of polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone, or pola-R-CHP, vs the well-known combination of rituxiumab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated diffuse LBCL.

A discussion, Novel Findings in CAR T-Cell Therapies for Hematologic Malignancies, with a live question and answer session, will take place Monday from 4:30 to 5:15 pm. The session chair will be Marcela V. Maus, MD, Massachusetts General Hospital and Harvard Medical School; panelists will be Maus; David Baker, PhD, University of Washington; and Marco Ruella, MD, University of Pennsylvania.

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Use of CAR T-Cell Therapy in LBCL Could Come Earlier After ASH 2021 - AJMC.com Managed Markets Network

DUBLIN--(BUSINESS WIRE)--The "Global Stem Cell Partnering Terms and Agreements 2010-2021" report has been added to ResearchAndMarkets.com's offering.

This report provides comprehensive understanding and unprecedented access to the stem cell partnering deals and agreements entered into by the worlds leading healthcare companies.

The report provides a detailed understanding and analysis of how and why companies enter Stem Cell partnering deals. These deals tend to be multicomponent, starting with collaborative R&D, and proceed to commercialization of outcomes.

This report provides details of the latest Stem Cell agreements announced in the life sciences since 2010.

One of the key highlights of the report is that over 650 online deal records of actual Stem Cell deals, as disclosed by the deal parties, are included towards the end of the report in a directory format - by company A-Z, stage of development, deal type, therapy focus, and technology type - that is easy to reference. Each deal record in the report links via Weblink to an online version of the deal.

In addition, where available, records include contract documents as submitted to the Securities Exchange Commission by companies and their partners. Whilst many companies will be seeking details of the payment clauses, the devil is in the detail in terms of how payments are triggered - contract documents provide this insight where press releases and databases do not.

A comprehensive series of appendices is provided organized by Stem Cell partnering company A-Z, stage of development, deal type, and therapy focus. Each deal title links via Weblink to an online version of the deal record and where available, the contract document, providing easy access to each deal on demand.

The report also includes numerous tables and figures that illustrate the trends and activities in Stem Cell partnering and dealmaking since 2010.

In conclusion, this report provides everything a prospective dealmaker needs to know about partnering in the research, development and commercialization of Stem Cell technologies and products.

Key benefits

Global Stem Cell Partnering Terms and Agreements 2010-2021 provides the reader with the following key benefits:

Companies Mentioned

Key Topics Covered:

Executive Summary

Chapter 1 - Introduction

Chapter 2 - Trends in Stem Cell dealmaking

2.1. Introduction

2.2. Stem Cell partnering over the years

2.3. Most active Stem Cell dealmakers

2.4. Stem Cell partnering by deal type

2.5. Stem Cell partnering by therapy area

2.6. Deal terms for Stem Cell partnering

2.6.1 Stem Cell partnering headline values

2.6.2 Stem Cell deal upfront payments

2.6.3 Stem Cell deal milestone payments

2.6.4 Stem Cell royalty rates

Chapter 3 - Leading Stem Cell deals

3.1. Introduction

3.2. Top Stem Cell deals by value

Chapter 4 - Most active Stem Cell dealmakers

4.1. Introduction

4.2. Most active Stem Cell dealmakers

4.3. Most active Stem Cell partnering company profiles

Chapter 5 - Stem Cell contracts dealmaking directory

5.1. Introduction

5.2. Stem Cell contracts dealmaking directory

Chapter 6 - Stem Cell dealmaking by technology type

Chapter 7 - Partnering resource center

7.1. Online partnering

7.2. Partnering events

7.3. Further reading on dealmaking

For more information about this report visit https://www.researchandmarkets.com/r/ti6e58

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Global Stem Cell Partnering Terms and Agreements 2021 Report - Featuring Regenetech, Stempeutics and Arthrex Among Others - ResearchAndMarkets.com -...

Stem cell therapy, sometimes called regenerative medicine, is one of the most exciting areas of the life sciences sector right now.

Since the pandemic, the sector has emerged into the publics spotlight with new developments in mRNA-based vaccines and therapies.

Nasdaq is the obvious breeding ground for world-class stem cell companies with the likes of Moderna and BioNTech, and lesser known names like Anavex and Enochian.

In Australia, Mesoblast (ASX:MSB) has long been the local poster child for the regenerative medicine industry.

Mesoblast has developed a platform of innovative cellular medicines, but the company has struggled since the FDA rejected its drug in October last year.

Now, other ASX companies like Cynata Therapeutics (ASX:CYP)are making rapid progress to take over the mantle from MSB in this hot field.

Cynata is developing a mesenchymal stem cells (or MSC) technology, which it says has huge therapeutic potential for numerous unmet medical needs.

This includes asthma, heart attack, sepsis, and acute respiratory distress syndrome (ARDS), which all add up to a market opportunity worth $46bn, says the company.

According to CEO Dr Ross Macdonald, who spoke to Stockhead today, MSC is the hottest segment of stem cell therapy at the moment, and has gained a lot of attention recently.

There is a huge interest, and theres been more than 1000 clinical trials conducted around the world using MSC, Dr Macdonald told Stockhead.

He explains that the humans immune system controls many of the bodys functions responsible for repairing tissue after injury or disease, and defending against invading germs like viruses or bacteria.

And just like an orchestral conductor, MSC seems to be playing a central role in that coordination within our immune system.

We now have a firm understanding of how those cells coordinate the bodys responses, and can use that knowledge to enhance those processes that they control, Dr Macdonald explained.

In short, MSC therapies work by expressing a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation.

And because MSCs play that co-ordination role within the immune system, they can be used to treat different diseases.

However theres one big problem with cell-based therapies, and its not to do with the safety and efficacy.

Its how to manufacture these products on a mass scale, that is the greatest challenge right now, says Dr Macdonald.

Unlike aspirin where it can be synthesised in a chemical lab and produced in bulk, manufacturing a living drug like a cell is a whole lot more complicated.

But that big challenge is the exact area of strength and competitive advantage that Cynata has, Dr Macdonald told Stockhead.

He says Cynata has a technology platform which allows it to manufacture essentially limitless quantities of MSCs, consistently and economically.

Dr Macdonald explains there are two approaches to using cell therapy, the autologous and the allogeneic approach.

The autologous approach is where the patient themselves serves as their own donor.

This is obviously bespoke and inefficient, because the drug can only be manufactured for that one patient, and is obviously not an industrialised process, he said.

But by taking an allogeneic approach, Cynata has the ability to start with a one time donation of cells from one single donor.

Well never have to go back to that human donor ever again, so our process of producing cells has become a very much more typical industrialised process.

The company has a patent for this, with two clinical trials underway and two more under preparation.

A Phase 3 clinical trial for osteoarthritis which is funded by a NHMRC grant has progressed the furthest, while a Phase 2 trial in COVID-19 is ongoing.

Meanwhile a Phase 1 study in GvHD, which was published in prestigious journal Nature Medicine, is probably the closest to commercialisation according to Dr Macdonald.

GvHD is a challenging disease which occurs in patients who have had a bone marrow transplant as part of their chemotherapy treatment for cancer.

Chemo is still very much a sledgehammer therapy where you use very toxic drugs that do kill the cancer cells, but they also kill the surrounding healthy cells that grow hair and bone marrow.

Unfortunately for many patients, the bone marrow transplant reacts against their body and starts to attack all of the tissues in the body, and its ultimately fatal.

Its a horrible death, destroying the lungs, liver, intestines and the skin, Macdonald explains.

Cynatas MSC therapy has been shown to reset that reaction, so the patient can recover from the GvHD, and also recover from their underlying cancer.

With all these clinical trials concurrently under way, Macdonald believes there is a clear significant upside potential for Cynata, particularly given its small market cap of $70m compared to other similar plays like Mesoblast ($1 billion market cap).

Osteopore (ASX:OSX) focuses in bones and specialises in the production of 3D printed bioresorbable implants that are used in surgical procedures to assist with the natural stages of bone healing.

The 3D bio-printer makes a scaffold that mimics bone, with a patented micro-architecture which traps the patients own stem cells.

Orthocell (ASX:OCC) develops collagen medical devices and cellular therapies for the repair and regeneration of human tendons, bone, nerve and cartilage defects.

Its flagship product, the CelGro, is a naturally derived collagen medical device for tissue repair.

Aroa Biosurgery (ASX:ARX) develops FDA-approved medical devices for wounds and tissue repair using its extracellular matrix (ECM) technology, mainly in the United States.

Recent study shows 100% success rates from the use of its Myriad product when patients underwent surgical reconstruction of exposed vital structures such as bone and tendon.

Regeneus (ASX:RGS) Progenza is a cellular therapy targeting pain and inflammation which uses Secretome to improve not only the resident tissue, but the MSCs themselves.

It fills a gap in the current treatment market for osteoarthritis, by providing disease modification and pain relief to address patient symptoms.

Anteris Technologies (ASX:AVR) claims that its Adapt Technology is the first and only bio-scaffold technology that completely re-engineers xenograft tissue into a pure collagen scaffold.

A recent study indicated that Adapt-treated tissue has superior anti-calcification attributes compared with tissues used in competitor valves.

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Mesoblast has long been the one poster child for stem cell therapy. Now Cynata and other ASX stocks have e ... - Stockhead