Catherine S. Diefenbach, MD, Talks Future of CAR T-cell Therapy Following Liso-Cel Approval in Second-Line LBCL – Cancer Network

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Catherine S. Diefenbach, MD, spoke about refining understanding of CAR T-cell therapies after the approval of lisocabtagene maraleucel for patients with relapsed/refractory large B-cell lymphoma.

Lisocabtagene maraleucel (liso-cel; Breyanzi) was recently approved for the second-line treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma not otherwise specified; high-grade B-cell lymphoma; primary mediastinal LBCL; and grade 3B follicular lymphoma.1 CancerNetwork spoke with Catherine S. Diefenbach, MD, director of both Hematology and Translational Research and the Clinical Lymphoma Program of Perlmutter Cancer Center at NYU Langone Health, about data from the phase 3 TRANSFORM trial (NCT03575351) that led to the approval and how the indication for this and other similar therapies may be expanded in the future with better understand regarding how to tailor the therapy.2

There are a couple of steps that are going to be important. One is to get a better idea of who benefits so we can tailor this therapy to the patients who are going to benefit the most. We need to get better at understanding the mechanisms of relapse and nonresponse to CAR T-cell therapy so that we [avoid subjecting] patients to this toxic therapy who are unlikely to benefit and/or design a next-generation CAR T-cell treatment that is going to allow more patients to have a durable response and be cured than what is currently approved. We need to get better at managing the toxicity of CAR T cells because this is still a fairly toxic therapy, and design next-generation CAR T cells that are less toxic. We need to get better about improving access so more patients can have access to CAR T cells. There are still many issues around insurance and payments for commercial CAR T cells. From a drug development, a clinical, and a public health standpoint, theres still much work that we can do to optimize this therapy.

This is an exciting time in lymphoma. We have a new therapy that was approved initially in the third line thats now moving to the second line and other exciting therapies that are nearing approval. We have more ways than ever to cure patients with lymphoma or extend the lives of people with incurable lymphoma. The challenge going forward is going to understand who benefits from which therapy and understand how to optimize response for all patients with these exciting therapies that we now have. This is an absolutely wonderful and transformative development.

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Catherine S. Diefenbach, MD, Talks Future of CAR T-cell Therapy Following Liso-Cel Approval in Second-Line LBCL - Cancer Network

Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal…

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Preclinical evaluation of FasT CAR-T cellsFasT CAR-T (F-CAR-T) proliferation in vitro

To characterize the in vitro proliferative capacity of F-CAR-T cells, F-CAR-T and C-CAR-T cells were manufactured in parallel (Supplementary Methods, and Fig. S1) using T-cells from 6 B-ALL patients. To investigate the ex vivo proliferation of F-CAR-T, frozen CD19 F-CAR-T and C-CAR-T cells from each patient were thawed and stimulated with irradiated CD19-expressing K562 cells. The number of CD19-targeting CAR-T cells was then determined during the course of cell expansion in vitro. As shown in Fig. 1A, upon CD19 antigen stimulation, F-CAR-T proliferation was much more robust compared to C-CAR-T proliferation. On day 17 post co-culture, F-CAR-T expanded 1205.61226.3 fold (MeanSD), while C-CAR-T expanded only 116.437.2 fold (MeanSD), (p=0.001). To characterize the mechanism underlying the superior proliferative ability of F-CAR-T, we purified CD19+ CAR-T cells from both F-CAR-T and C-CAR-T. The expression of genes involved in cell proliferation, cell cycle, and apoptosis was analyzed using Nanostring (detailed gene sets are in Table S2). Gene expression profiles showed higher F-CAR-T expression scores for genes associated with cell cycle regulation (F-CAR-T vs. C-CAR-T, p<0.01) and lower expression scores for apoptosis-related genes (F-CAR-T vs. C-CAR-T, p<0.05) in F-CAR-T cells (Fig. S2A).

A Ex vivo cell proliferation of F-CAR-T and C-CAR-T derived from B-ALL patients (n=6) (***P=0.001, F-CAR-T vs. C-CAR-T, d17, unpaired student two-tailed t-test). B Tscm, Tcm, and Tem were characterized by surface staining of CD45RO and CD62L and analyzed with flow cytometry (***P<0.001 comparing F-CAR-T and C-CAR-T). C T-cell exhaustion was characterized by PD-1, LAG3, and TIM-3 staining; Statistical analyses of the percentage of PD1+ LAG3+ Tim3+ (***P<0.001, comparing F-CAR-T and C-CAR-T), unpaired student two-tailed t-test). D RTCA assay was used to examine the specific killing of HeLa-CD19 cells. Growth of target HeLa-CD19 or HeLa cells were monitored dynamically. E CD19+ target Nalm6-Luc cells or F Raji-Luc cells were co-cultured with either F-CAR-T or C-CAR-T for 6h. Target cell killing efficacy was calculated by luciferase activity. NS, P>0.05 F-CAR-T vs. C-CAR-T (unpaired student t-test, two-tailed). F-CAR-T FasT CAR-T, C-CAR-T conventional CAR-T, Tcm (CD45RO+CD62L+) T central memory cells, Tem (CD45RO+CD62L) T effector memory cells, Tscm (CD45ROCD62L+) T stem cell memory, PD1 programmed cell death protein 1, TIM-3 T cell immunoglobulin and mucin domain containing-3, LAG3 lymphocyte-activation gene 3, RTCA real-time cell analyzer, E:T effector cells: target cells, NT normal T-cell.

Phenotypes of unstimulated F-CAR-T from three healthy donors were analyzed by flow cytometry. The CD45ROCD62L+ population was 45.7%2.2% which was comparable to the un-transduced T-cells (data not shown). Upon stimulation with CD19+ tumor cells for 9 days, C-CAR-T central memory cells (Tcm, CD45RO+CD62L+ and effector memory cells (Tem, CD45RO+CD62L) were 56.62%11.97% and 40.48%9.70%, respectively, among the C-CAR-T cells (Fig. 1B and Figs. S2B and S2). In contrast, Tcm cells (87.92%4.36%) was predominant in F-CAR-T, with only a small fraction of Tem (7.84%3.79%). In addition, F-CAR-T cells demonstrated more abundant T stem cell memory (Tscm) (3.841.22% vs 2.342.48%, p<0.05) than C-CAR-T cells. We also examined the exhaustion status of the stimulated CAR-T cells. A higher percentage of PD-1+LAG3+Tim3+T-cells were detected in the C-CAR-T (11.19%2.54%) compared to F-CAR-T (3.59%2.51%, p<0.001) (Fig. 1C). Together these data indicated that the F-CAR-T exhibited a younger phenotype and was less exhausted compared to C-CAR-T.

We used a real-time cell analyzer (RTCA) assay to measure the cytotoxicity of F-CAR-T and C-CAR-T against CD19+ cells in vitro. F-CAR-T and C-CAR-T killing of Hela-CD19 target cells were comparable using this assay (Fig. 1D). Similar levels of IFN- and IL-2 production were also observed (Fig. S2D). In a luciferase-based cytotoxicity assay, CD19+ B leukemia cell lines, Raji and Nalm6, were both effectively killed to similar or better levels at different E:T ratios (Fig. 1E, F).

To compare the in vivo cytotoxicity of F-CAR-T and C-CAR-T, severe immunodeficient NOG mice were engrafted with Raji-luciferase cells. One week after the tumor grafts were established, F-CAR-T and C-CAR-T were intravenously injected at various doses. The engrafted tumors progressed aggressively in control groups with either vehicle alone or control T-cells (Fig. 2A). In contrast, F-CAR-T or C-CAR-T treatment greatly suppressed tumor growth in a dose-dependent manner (Fig. 2A). In the high dose group (2106/mice), both F-CAR-T and C-CAR-T eliminated the tumor rapidly. However, in the low dose group (5105/mice), F-CAR-T showed more effective tumor-killing compared to C-CAR-T. On day 20, mice in the low dose F-CAR-T group became tumor-free, while C-CAR-T treated mice exhibited tumor relapse (Fig. 2A). We examined the CAR-T cell expansion in vivo after infusion. As shown in Fig. 2B, both F-CAR-T and C-CAR-T began to expand in the peripheral blood 7 days after infusion. C-CAR-T cell numbers reached their peak on day 14 and receded on day 21. In contrast, the F-CAR-T cell number peaked on day 21 and declined to a baseline level on day 28. F-CAR-T not only persisted longer but also underwent 26 folds greater expansion than C-CAR-T (Fig. 2B).

A Raji-Luc cell engraftment NOG mice were given high dose (2106/mice, n=3) and low dose (5105/mice, n=3) F-CAR-T/C-CAR-T along with control groups. Tumor growth was monitored with IVIS scan once every 3 days; B CAR-T expansion in peripheral blood of mice was analyzed by flow cytometry (n=6). ***P<0.001 for F-CAR-T HD vs. C-CAR-T HD; F-CAR-T LD vs. C-CAR-T LD; F-CAR-T HD vs. F-CAR-T LD; C-CAR-T HD vs. C-CAR-T LD (two-way ANOVA statistical analysis); C Schematic of the Nalm6 (1106) xenograft model, CAR-T (2106) infused 1 day after cyclophosphamide (20mg/kg) treatment. Bone marrow infiltration of F-CAR-T was analyzed 10 days after CAR-T infusion (n=3); D CD45+CD2 F-CAR-T vs. C-CAR-T in peripheral blood of mice were analyzed by flow cytometry; *P<0.05 (unpaired student two-tailed t-test). IVIS in vivo imaging system, PB peripheral blood, i.v. intravenous, HD high dose, LD low dose, Cy cyclophosphamide; *p<0.05; #: number.

We examined the BM infiltration of F-CAR-T cells after infusion into Nalm6-bearing mice (Fig. 2C). A larger population of CAR-T cells was observed 10 days after infusion in BM in F-CAR-T infused group than that in the C-CAR-T group (p<0.05) (Fig. 2D), suggesting F-CAR-T cells possessed a better BM homing capability than C-CAR-T.

The chemokine receptor CXCR4 is known to be critical for BM homing of T-cells [25, 26]. Indeed, a higher percentage of CXCR4+ T cells were detected in F-CAR-T than in the C-CAR-T. Interestingly, this phenotype was more pronounced for CD4+ T cells than CD8+ T cells (Fig. S3A). In a two-chamber system, more F-CAR-T cells could be detected in the lower chamber than their C-CAR-T counterparts (Fig. S3B).

Between Jan. 2019 and Oct. 2019, 25 pediatric and adult patients with CD19+R/R B-ALL were enrolled onto our phase 1 trial, including two patients who had relapsed following a prior allo-HSCT. Patient characteristics are detailed in Table 1. The median age of patients was 20 (range: 344) years old. Twenty patients were >14 years old, and five were 14 years old. The median percentage of pre-treatment BM blasts was 9.05% (range: 0.1982.9%). As our pre-clinical studies demonstrated that F-CAR-T cells had a superior expansion capability as compared to C-CAR-T, we infused a relatively low doses of F-CAR-T cells, ranging from 104105 cells/kg: 3.0104 cells/kg (n=2), 6.5 (5.867.43)104 cells/kg (n=9), 1.01 (1.01.16)105 cells/kg (n=12), 1.52(1.471.56)105 cells/kg (n=2), (Fig. S4). The median time from apheresis to the infusion of CD19+F-CAR-T cells was 14 days (range: 1220). Although the manufacturing time of F-CAR-T was next day, the quality control time and detailed final product releases including sterility testing require a minimum of 710 days to complete. In addition, transportation of cell products requires approximately two days. Of the 25 patients who received CD19 F-CAR-T infusion, 22 (88%) received bridging chemotherapy between apheresis and lymphodepleting chemotherapy to control rapid disease progression (Table S3).

F-CAR-T cells were manufactured successfully for all patients. The mean transduction efficiency of F-CAR-T was 35.4% (range: 13.170.3%) (Fig. S5A). Both CD4+/CAR+ (mean, 49.6%; range: 13.673.2%) and CD8+/CAR+ (mean, 41.5%; range: 20.677.7%) subsets were present in the CD3+CAR+ T cell subsets of all products. The mean proportion of Tscm, Tem, and Tcm cells in the CD3+CAR+ T cell subsets of all products was 23.3% (range: 3.5545.3%), 33.2% (range: 17.267.9%), and 36.1% (range: 20.758.1%), respectively (Fig. S5B). F-CAR-T products exerted significant IFN- release and cytotoxic effects against the CD19+ cell line HELA-CD19 (Fig. S5, C, D).

All 25 infused patients experienced adverse events (AEs) of any grade, with 25 (100%) experiencing grade 3 or higher adverse events. No grade 5 events related to F-CAR-T treatment were observed (Table 2).

CRS occurred in 24 (96%) patients with 18 (72%) grade 12 CRS,6 (24%) of grade 3, and no grade 4 or higher CRS (Fig. S6). In the >14 years old group, 16/20 (80%) patients developed mild CRS, and only 2/20 (10%) developed grade 3 CRS. For 14 years old patients, 2/5 (40%) had mild CRS, yet 3/5 (60%) experienced grade 3 CRS (Table S4). ICANS was observed in 7 (28%) patients, with 2 (8%) grade 3 ICANS occurring in patients >14 years old and 5 (20%) grade 4 ICANS all occurring in patients 14 years old. No grade 5 ICANS was developed (Fig. S7 and Table S4). The most frequent presentation of CRS was fever, particularly a high fever of >39C. The first onset of CRS symptoms occurred between day 3 and 8 post-CAR-T infusion with a median onset at day 4 (range: 110 days). The most common symptoms of ICANS were seizure (5/7) and depressed consciousness (5/7). The median time to ICANS onset from CAR-T cell infusion was 7 days (range: 58), and the median time to resolution was 2 days (Fig. S7). All CRS and ICANS events were managed including early intervention when fever of 39C persisted for 24h. Sixteen (64%) patients received tocilizumab with a median total dose of 160mg (range: 160320mg). Twenty-one (84%) patients received corticosteroids including dexamethasone (median total dose, 43mg; range: 4127mg) and or methylprednisolone (median total dose, 190mg; range: 401070mg). The vast majority of these patients discontinued corticosteroids within 2 weeks. The change in IL-6, IFN-, IL-10, and GM-CSF levels after infusion are selectively shown in Fig. S8. The peak levels of these four cytokines were observed between day 710. Among all 21 cytokines examined, only post-infusion IL-6 levels were associated with moderate to severe CRS and/or ICANS (Figs. S9 and S10).

Superior in vivo proliferation and persistence of F-CAR-T compared to C-CAR-T cells were observed regardless of dose levels. The median peak level was reached on day 10 (range: 714 days) with 1.9105 transgene copies/g of genomic DNA (range: 0.225.2105 transgene copies/g of genomic DNA) by qPCR and 83 F-CAR-T cells per l blood (range: 42102 F-CAR-T cells per l blood) by FCM (Fig. 3A, B). No significant differences were observed among the different dose groups in the mean F-CAR-T copies peak (Fig. 3C). Importantly, there was no significant difference in the mean F-CAR-T copies peak between patients who received corticosteroids compared to those who did not (Fig. 3D).

A F-CAR-T cells in peripheral blood by qPCR. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; B F-CAR-T cells in peripheral blood by flow cytometry. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; C Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood at each dose level. Statistical significance was determined by the MannWhitney test. D Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood with or without steroids. Statistical significance was determined by the MannWhitney test.

Fourteen days after F-CAR-T cell infusion, all patients achieved morphologic CR including 2/25 with CR and 23/25 CR with incomplete hematologic recovery (CRi), which further improved to 11/25 CR and 14/25 CRi 28 days post F-CAR-T (Table 1 and Fig. 4). More importantly, 23/25 (92%) had the minimal residual disease (MRD)-negative remission on day 14 and day 28 after F-CAR-T treatment. Patients achieving remission through CAR-T were given the option to proceed to allo-HSCT. With a median time of 54 days (range: 4581 days) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status decided to pursue consolidative allo-HSCT including one patient who received a 2nd transplant. As of 18 October 2021, with a median follow-up duration of 693 days (range: 84973 days) among the 20 patients who had received allo-HSCT, one patient relapsed on day 172 and died 3 months after relapse, and four patients died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The other 15 patients remained in MRD-negative CR with a median remission duration of 734 days (range: 208973) except for one who became MRD-positive on day 294 with CD19+ disease. Among the other three patients (F05, F06, F16), one remained in MRD-negative CR on day 304, one remained in MRD-negative CR until day 303, received allo-HSCT but died from an infection on day 505, and one was lost to follow-up after day 114. Two patients who had MRD-positive CR after infusion withdrew from the study on day 42 and day 44, respectively, to seek other studies.

Clinical outcomes and consolidative allo-HSCT for the 25 patients who were treated with F-CAR-T therapy are shown. On day 28, 23/25 patients achieved MRD-negative CR/CRi. With a median time of 54 days (range: 4581) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status received consolidative allo-HSCT. Among the 20 patients, 1 patient (F23) relapsed on day 172 and died 3 months after relapse. Four patients (F04, F09, F11, F12) died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The remaining 15 patients were in MRD-negative CR except for one (F18) who became MRD-positive on day 294. Among the other 3 patients (F05, F06, F16), 1 remained MRD-negative CR on day 304, 1 remained in MRD-negative CR until day 303, received allo-HSCT, and subsequently died from an infection on day 505. One patient was lost to follow-up after day 114. MRD minimal residual disease, CR complete remission, Allo-HSCT allogeneic hematopoietic stem cell transplantation.

F-CAR-T/T ratio in cerebrospinal fluid (CSF) was evaluated by FCM in 13/25 patients with available samples (Table S5). Between days 10 and 32, 9 patients were found to have considerable F-CAR-T penetration in their CSF, ranging from 40.65 to 79.2%, including 4 who developed severe ICANS. Among the other 4 patients, F-CAR-T cell abundance in the CSF ranged from 1.29% to 3.57%, and none experienced severe ICANS. Patients with higher levels of CAR-T in PB on day 10 consistently had higher levels of CAR-T in CSF with the exception of patient F15. Notably, CAR-T cells were still detectable in the CSF on day 101 with a 2.36% CAR-T/T ratio in patient F06, who also had undetectable circulating CAR-T cells at the same time.

In addition, concentrations of seven cytokines (IL-1b, IL-6, IL-10, IFN-, TNF-, MCP-1, and GM-CSF) in CSF samples from the above 10 of 13 patients were measured. Specifically, IL-1b was not detected in any of the 10 patients, and only one patient had detectable GM-CSF. For the other five cytokines, patients with severe ICANS had higher IL-6 levels in contrast to patients without severe ICANS, and the difference between the median level of IL-6 among these two groups of patients was statistically significant (Fig. S11). We did not observe significant differences among the other 4 cytokines between the two groups of patients. No clear relation between the CSF cytokine levels and the F-CAR-T/T % was observed.

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Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal...

Jasper Therapeutics to Participate in the William Blair 42nd Annual Growth Stock Conference – GuruFocus.com

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REDWOOD CITY, Calif., June 07, 2022 (GLOBE NEWSWIRE) -- Jasper Therapeutics, Inc. ( JSPR), a biotechnology company focused on enabling cures with stem cell therapies, today announced that the Company is participating in the William Blair 42nd Annual Growth Stock Conference, to be held in Chicago from June 6-9, 2022.

Ronald Martell, Jaspers Chief Executive Officer, is scheduled to present on Thursday, June 9th at 8:00AM CT, with a breakout session to follow at 8:40AM CT. A live webcast of the presentation will be available at https://wsw.com/webcast/blair66/jasp/1933236 and at the Companys Investor Events webpage.

About Jasper TherapeuticsJasper Therapeutics, Inc. is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The company is advancing two potentially groundbreaking programs. JSP191, an anti-CD117 monoclonal antibody, is in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow in patients undergoing hematopoietic cell transplantation. It is designed to enable safer and more effective, and potentially curative, allogeneic hematopoietic cell transplants and gene therapies. A clinical study of JSP191 as a novel, disease-modifying, therapeutic for patients with lower risk MDS is also planned to begin in 2022. In parallel, Jasper Therapeutics, Inc. is advancing its preclinical mRNA hematopoietic stem cell grafts platform, which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts. Both innovative programs have the potential to transform the field and expand hematopoietic stem cell therapy cures to a greater number of patients with life-threatening cancers, genetic diseases and autoimmune diseases than is possible today. For more information, please visit us at jaspertherapeutics.com.

Forward-Looking StatementsCertain statements included in this press release that are not historical facts are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements are sometimes accompanied by words such as believe, may, will, estimate, continue, anticipate, intend, expect, should, would, plan, predict, potential, seem, seek, future, outlook and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding the potential of the Companys JSP191 and mRNA engineered stem cell graft programs. These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of Jasper and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, an assurance, a prediction or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Jasper. These forward-looking statements are subject to a number of risks and uncertainties, including general economic, political and business conditions; the risk that the potential product candidates that Jasper develops may not progress through clinical development or receive required regulatory approvals within expected timelines or at all; risks relating to uncertainty regarding the regulatory pathway for Jaspers product candidates; the risk that prior study results may not be replicated; the risk that clinical trials may not confirm any safety, potency or other product characteristics described or assumed in this press release; the risk that Jasper will be unable to successfully market or gain market acceptance of its product candidates; the risk that Jaspers product candidates may not be beneficial to patients or successfully commercialized; patients willingness to try new therapies and the willingness of physicians to prescribe these therapies; the effects of competition on Jaspers business; the risk that third parties on which Jasper depends for laboratory, clinical development, manufacturing and other critical services will fail to perform satisfactorily; the risk that Jaspers business, operations, clinical development plans and timelines, and supply chain could be adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic; the risk that Jasper will be unable to obtain and maintain sufficient intellectual property protection for its investigational products or will infringe the intellectual property protection of others; and other risks and uncertainties indicated from time to time in Jaspers filings with the SEC. If any of these risks materialize or Jaspers assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. While Jasper may elect to update these forward-looking statements at some point in the future, Jasper specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Jaspers assessments of any date subsequent to the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements.

Contacts:

John Mullaly (investors)LifeSci Advisors617-429-3548[emailprotected]

Jeet Mahal (investors)Jasper Therapeutics650-549-1403[emailprotected]

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Jasper Therapeutics to Participate in the William Blair 42nd Annual Growth Stock Conference - GuruFocus.com

Orthobiologics Market is Predicted to Expand at a CAGR of 4.7% during the Forecast Period, notes TMR Study – GlobeNewswire

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Wilmington, Delaware, United States, July 04, 2022 (GLOBE NEWSWIRE) -- Transparency Market Research Inc.: The value of the global orthobiologics market was clocked at US$ 5.01 Bn in 2021. The orthobiologics marketoutlook predicts the market to rise at a CAGR of 4.7% during the forecast period, from 2022 to 2031. The global orthobiologics market is expected to attain a value surpassing US$ 7.4 Bn by 2031. Until afew years ago, orthobiologics have been a common practice in sports medicine andorthopedic surgeries. Demand analysis of orthobiologics estimates that developments in regenerative medicine, an increasing number of sports andsports-relatedinjuries, rising demand for less invasive procedures, andconstant infusion of innovative products and treatmentsare all expected to propel the global orthobiologics market.

Musculoskeletal tissue engineering and regenerative medicineresearch, however, have slowed down as a result of the COVID-19 outbreak. However,strong development potential in developing nations and a rise in demand for cutting-edge therapies are expected to create considerable prospects for companies in the growth of the orthobiologics market.

The global orthobiologics market is being driven by the increase in orthobiologics product and usage oforthopedic device. In addition to that, there is increasingincorporation of biochemistry andbiology in the treatment of soft tissue andbone injuries. Orthobiologic drugs help natural healing mechanism of the bodyto workmore quickly. They can hasten the healing of injured ligaments, tendons, andmuscles. It alsoassistsin repairing osteoarthritis damage. The materials used to develop orthobiologics are those that are normally present in the human body.

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Global Orthobiologics Market: Growth Drivers

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Global Orthobiologics Market: Segmentation

Product Type

Modernization of healthcare in terms of both infrastructure and services have pushed the healthcare industry to new heights, Stay Updated with Latest Healthcare Industry Research Reports by Transparency Market Research:

Stem Cells Market: The global stem cells market is expected to reach the value of US$ 25.68 Bn by the end of 2028.It is estimated to expand at a CAGR of 10.4% from 2021 to 2028.

Placental Stem Cell Therapy Market: The placental stem cell therapy market stood at US$ 0.5 Bn in 2019 and is expected to cross a revenue of US$ 4.4 Bn by the end of 2030.

Platelet Rich Plasma and Stem Cell Alopecia Treatment Market: The global platelet rich plasma & stem cell alopecia treatment market is expected to reach a value of approximately US$ 450.5 Mn by the end of 2026, expanding at a high single digit CAGR during the forecast period.

Soft Tissue Allografts Market: The global soft tissue allografts market was valued at US$ 3.55 Bn in 2018, and is projected to reach ~ US$ 6.2 Bn by 2027, expanding at a CAGR of ~ 6.5% from 2019 to 2027.

Bone Growth Stimulators Market: The global bone growth stimulators market is anticipated to reach more than US$ 2 Bn by the end of 2031. The global market is projected to grow at a CAGR of 5.8% from 2022 to 2031.

Small Bone and Joint Orthopedic Devices Market: The global small bone and joint orthopedic devices market was valued at US$ 5.5 Bn in 2018 and is anticipated to expand at a CAGR of 6.3% from 2019 to 2027.

Metastatic Bone Disease Market: The global metastatic bone disease market was valued at US$ 12,450.0 Mn in 2017 and is anticipated to reach US$ 24,886.8 Mn by 2026, expanding at a CAGR of 8.1% from 2018 to 2026.

Bone Grafts and Substitutes Market: The global bone grafts and substitutes market is expected to cross the value of US$ 4.4 Bn by the end of 2028. It is estimated to expand at a CAGR of 4.9% from 2021 to 2028.

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Orthobiologics Market is Predicted to Expand at a CAGR of 4.7% during the Forecast Period, notes TMR Study - GlobeNewswire

Akari Therapeutics Announces First Patient to Complete Course of Treatment in the Phase III Part A Clinical Trial of Investigational Nomacopan in…

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NEW YORK and LONDON, July 07, 2022 (GLOBE NEWSWIRE) -- Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biotechnology company focused on developing advanced therapies for autoimmune and inflammatory diseases, today announced that a patient has completed the course of investigational nomacopan treatmentin the open-label, multi-center Phase IIIPart Aclinical trial in pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA). Nomacopan is a bispecific recombinant inhibitor of complement C5 and leukotriene B4 (LTB4).

Three patients with severe (nephrotic range proteinuria and elevated soluble C5b-9) HSCT-TMA have been enrolled in the clinical trial. One patient completed more than 60 days of nomacopan treatment and subsequently was discharged from the hospital. Another patient died from multi-organ failureunrelated to nomacopan treatment.Dosing has begun in the third patient.

This is promising news for children and families facing hematopoietic stem cell transplant-related TMAs who have unmet needs that are significant and urgent because there are no approved treatment options, said Rachelle Jacques, President and CEO of Akari Therapeutics. Recruitment into a study of treatment for a rare and emergent complication of stem cell transplants in children has inherent challenges, and it is testament to the passion and commitment of everyone involved that this important Phase III clinical trial is progressing on behalf of patients and their families.

Nomacopan was granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA) for pediatric HSCT-TMA. Data from the Phase III Part A study of nomacopan in HSCT-TMA will inform the pivotal Phase III Part B study that will be the basis for potential regulatory submissions in the U.S. and Europe.

The six-year-old patient who was discharged wastreated at a clinical trial site in Manchester, England by investigator Rob Wynn, M.D. Thrombotic microangiopathy following a stem cell transplant procedure is a rare but devastating complication made even more tragic because there are currently no approved treatments, said Professor Rob Wynn, of Royal Manchester Childrens Hospital, part of Manchester University NHS Foundation Trust. As we advance this important clinical trial and offer treatment to children in Manchester where formerly there was none, we are bringing new hope to families who are in desperate need, and to other clinicians who very much want to offer a treatment option.

Thrombotic microangiopathy following a stem cell transplant procedure is a rare but serious complication of HSCT that appears to involve complement activation, inflammation, tissue hypoxia and blood clots, leading to progressive organ damage and death. The mortality rate in patients who develop severe transplant-related TMAs is 80%.1 Currently, there are no approved treatment options in the U.S. or Europe.

Sites are open and recruiting in the U.S, U.K., and Poland for the Phase III Part A clinical trial of investigational nomacopan in pediatric patients who have undergone allogeneic or autologous HSCT and develop HSCT-TMA within a year of transplant. Patient dosing is underway in the multi-center, open-label study that has a recruitment goal of seven pediatric patients over six months old.

The primary study endpoints are either independence of red blood cell transfusion or urine protein creatinine ratio of 2 mg/mg maintained over 28 days immediately prior to any scheduled clinical visit up to Week 24. According to the study protocol, patients may discontinue therapy sooner than 24 weeks, if one, or both, of the primary endpoint components has been met and the treating clinician determines there is no longer a need for continued treatment with nomacopan. Patients who have achieved the primary endpoint and are no longer receiving nomacopan will have a follow-up clinic visit 30 days after the last dose, at 24 weeks and for long-term follow-up at one and two years.

References

About Akari Therapeutics

Akari Therapeutics, plc (Nasdaq: AKTX) is a biotechnology company focused on developing advanced therapies for autoimmune and inflammatory diseases. Akari's lead asset, investigational nomacopan, is a bispecific recombinant inhibitor of C5 complement activation and leukotriene B4 (LTB4) activity. The Akaripipeline includes two late-stage programs for bullous pemphigoid (BP) and thrombotic microangiopathy (TMA), as well as earlier stage research and development programs in eye and lung diseases with significant unmet need. For more information about Akari, please visit akaritx.com.

Cautionary Note Regarding Forward-Looking Statements

Certain statements in this press release constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward- looking statements reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward- looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control. Such risks and uncertainties for our company include, but are not limited to: needs for additional capital to fund our operations, our ability to continue as a going concern; uncertainties of cash flows and inability to meet working capital needs; an inability or delay in obtaining required regulatory approvals for nomacopan and any other product candidates, which may result in unexpected cost expenditures; our ability to obtain orphan drug designation in additional indications; risks inherent in drug development in general; uncertainties in obtaining successful clinical results for nomacopan and any other product candidates and unexpected costs that may result there; difficulties enrolling patients in our clinical trials; failure to realize any value of nomacopan and any other product candidates developed and being developed in light of inherent risks and difficulties involved in successfully bringing product candidates to market; inability to develop new product candidates and support existing product candidates; the approval by the FDA and EMA and any other similar foreign regulatory authorities of other competing or superior products brought to market; risks resulting from unforeseen side effects; risk that the market for nomacopan may not be as large as expected risks associated with the impact of the COVID-19 pandemic; inability to obtain, maintain and enforce patents and other intellectual property rights or the unexpected costs associated with such enforcement or litigation; inability to obtain and maintain commercial manufacturing arrangements with third- party manufacturers or establish commercial scale manufacturing capabilities; the inability to timely source adequate supply of our active pharmaceutical ingredients from third party manufacturers on whom the company depends; unexpected cost increases and pricing pressures and risks and other risk factors detailed in our public filings with the U.S. Securities and Exchange Commission, including our most recently filed Annual Report on Form 20-F filed with the SEC. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release and we undertake no obligation to update or revise any of these statements to reflect events or circumstances occurring after this press release. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release.

For more information

Investor Contact:Mike MoyerLifeSci Advisors(617) 308-4306mmoyer@lifesciadvisors.com

Media Contact:Eliza SchleifsteinSchleifstein PR (917) 763-8106eliza@schleifsteinpr.com

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Akari Therapeutics Announces First Patient to Complete Course of Treatment in the Phase III Part A Clinical Trial of Investigational Nomacopan in...

Global Lupus Market is Expected to Reach USD 4.3 Billion With CAGR of 12.41% By Forecast 2027 Says Maximize Market Research (MMR) – Digital Journal

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The Global Lupus Market Is Estimated To Grow To USD 4.3 Billion With A CAGR Of 12.41 Percent By 2027.

TheGlobal Lupus Markethas gained traction in the last decade, and from 2022 to 2027, it is expected to grow at a compound annual growth rate (CAGR) of 4.3 percent. Market revenue will have increased to USD 4.3 billion by the end of 2027, up from USD 1.88 billion in 2020.

Global Lupus Market Scope and Dynamics:

Due to factors such rising healthcare costs, a growing female population, rapid urbanisation, supportive government measures, rising rates of SLE disease, etc., the industry has been expanding over the past few years. Different groups and the government are doing a number of actions to educate people about SLE. Several research institutions are offering medicines and treatments to SLE patients with government funding. Government-funded trials for several novel medications are now underway. The Centers for Disease Control and Prevention (CDC) in the US frequently publish SLE disease statistics and alert the public to the diseases serious side effects, particularly in the female population.

The market is anticipated to expand quickly over the forecast period as a result of a number of current trends, including an increase in clinical trials, the use of stem cell therapy, increased public awareness, etc. One of the most promising emerging areas of medicine for the treatment of Global Lupus, particularly for patients who do not respond well to more conventional forms of treatment, may be stem cell therapy. Stem cell therapy is becoming more popular since it is a cutting-edge method for treating Global Lupus, which will boost the growth of the Global Lupus market.

One of the key elements anticipated to restrain the growth of the global Global Lupus therapeutic market over the forecast period is the negative effects of medications used to treat the disease. For instance, almost all patients receiving treatment for SLE report one or more side effects such nausea, vomiting, bone toxicity, and other symptoms, according to a paper published in the peer-reviewed, open access journal Global Lupus Science and Medicine in March 2018.

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Global Lupus Market Region Insights:

Geographically, the North America are expected to lead the Global Lupus market due to the growing need for better treatment choices, the diseases increasing prevalence, government initiatives for it, and the availability of reimbursement. In addition, the regions developed healthcare system and easy access to biologics are anticipated to support market growth.

The Global Lupus market is expected to place Europe in second place. The growth of R&D initiatives and the increased incidence of Global Lupus in the area are both credited with driving the market in this region.

China, Japan, South Korea, India, Australia, and the rest of Asia-Pacific make up the Asia-Pacific Global Lupus market. Due to the rising Global Lupus prevalence, the growing healthcare industry, and the increasing geographical development of major market participants, the Asia-Pacific region is anticipated to have the quickest growth.

Global Lupus Market Segmentation:

By Technique:

By Product:

By End-User:

By Region:

Key Players in Global Lupus Market:

To Get a Detailed Report Summary and Research Scope of the Global Lupus Market Click here:@https://www.maximizemarketresearch.com/market-report/global-lupus-market/65753/

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Maximize Market Research provides syndicated and custom B2B and B2C business and market research on high-growth emerging technologies, opportunities, and threats for companies in the chemical, internet of things, food and beverage, healthcare, pharmaceuticals, electronics and communications, aerospace, and defense. Maximize Market Research is best positioned to assess, estimate, and anticipate market size along with the competitive landscape of industries as businesses across the globe are battling to keep up with the pace of changing market, along with changing industrial, and technical conditions.

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Global Lupus Market is Expected to Reach USD 4.3 Billion With CAGR of 12.41% By Forecast 2027 Says Maximize Market Research (MMR) - Digital Journal

TC BioPharm Announces Formation of Scientific Advisory Board with Renowned Cell Therapy Experts – GuruFocus.com

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EDINBURGH, Scotland, May 18, 2022 /PRNewswire/ -- TC Biopharm (Holdings) PLC ("TC Biopharm" or the "Company") (NASDAQ: TCBP) (NASDAQ: TCBPW), a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and viral indications, announced today announced the formation of a scientific advisory board (SAB) to advance its gamma-delta T cell therapy, OmnImmune, for the treatment of Acute Myeloid Leukemia (AML).

"We are honored to have these remarkable and accomplished cell therapeutics and scientific leaders join TC BioPharm's Scientific Advisory Board," said Bryan Kobel, CEO of TC BioPharm. "These individuals have made significant contributions and pioneered breakthroughs in cell therapy research and therapeutics, and together, they bring a wealth of knowledge and experience for TC BioPharm, as we work to develop our proprietary therapies to treat blood cancers and develop our platform into other oncological areas. We wil continue to expand our SAB to bring other expertise in cell therapy modalities to reflect our ongoing R&D efforts as well. TCBP looks forward to the input of these outstanding individuals as we advance our platform technology in allogeneic gamma deltas and their contribution to our ongoing research and development efforts in a number of project areas."

Members of the TC BioPharm Scientific Advisory include;

Mark Bonyhadi, Ph D., will lead the SAB. He is a senior advisor to Qiming Venture Partners USA and former Vice President of Research at Juno Therapeautics (acquired by Celgene). Dr. Bonyhadi has more than 30 years of experience in biopharmaceutical leadership roles in the US, specifically in the research and development of commercially viable approaches to take cell and gene therapies, as well as regenerative medicines, from the lab to the clinic and for subsequent commercial development. Prior to his role as vice president of Research at Juno Therapeutics Inc (acquired by Celgene Corporation), he was Director of Global Business Development for Cell Therapy at Invitrogen (which merged to become Life Technologies and was subsequently acquired by Thermo-Fisher) and prior to that, Vice President ofResearch at Xycte Therapies and a Senior Scientist at SyStemix, Inc. He was formerly the chair of the Industry Liaison Committee for the American Society for Gene and Cell Therapy (2015-2016). He is also the inventor on 11 patents and an author on 40 publications. He currently is a member of the scientific advisory board for Akron Biotech and also serves as a Non-executive Director at TCBP and as a Non-executive Director at Integra Therapeutics.

Uma Lakshmipathy, Ph D., has two decades of experience in cell biology, stem cells and translational research. She is currently the Director of R&D in Science and Technology and Head of Patheon Translation Services in Pharma Services Group at Thermo Fisher Scientific. Her work is focused on developing end-to-end, standardized processes and analytics for cell therapy and support translational services destined towards cGMP manufacturing. She has a strong foundation in development of clinical-grade reagents and processes, viral and non-viral methods of cell modification and, analytical platforms for comprehensive cell therapy product characterization. As a junior faculty at the Stem Cell Institute, University of Minnesota, she was involved in ex vivo gene repair of disease mutations in adult stem cells. She has a doctoral degree in Molecular Biophysics from the Center for Cellular and Molecular Biology in India, postdoctoral experience in DNA double strand break repair from University of Minnesota Medical School and has authored several scientific publications, books and patents.

Erin Adams, Ph D., is the Joseph Regenstein Professor of Biochemistry and Molecular Biology at the University of Chicago and an expert in molecular immunology. She explores the molecular cues that the human immune system uses to distinguish between healthy and diseased tissue. Her primary focus is on unconventional, tissue resident effector cells in the human immune system including T cells, MR1-restricted and CD1-restricted T cells. Her laboratory research seeks to understand the role of these cells types in the immune response process and what signals regulate their activity in tissue homeostasis and disease. She has received multiple honors, including being named a Searle Scholar, a Kavli Fellow and awarded a Cancer Research Foundation Junior Investigator Award.

About TC BioPharm (Holdings) PLCTC BioPharm is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of gamma-delta T cell therapies for the treatment of cancer and viral infections with human efficacy data in acute myeloid leukemia. Gamma-delta T cells are naturally occurring immune cells that embody properties of both the innate and adaptive immune systems and can intrinsically differentiate between healthy and diseased tissue. TC BioPharm uses an allogeneic approach in both unmodified and CAR modified gamma delta t-cells to effectively identify, target and eradicate both liquid and solid tumors in cancer.

TC BioPharm is the leader in developing gamma-delta T cell therapies, and the first company to conduct phase II/pivotal clinical studies in oncology. The Company is conducting two investigator-initiated clinical trials for its unmodified gamma-delta T cell product line - Phase 2b/3 pivotal trial for OmnImmune in treatment of acute myeloid leukemia and Phase I trial for ImmuniStim in treatment of Covid patients using the Company's proprietary allogenic CryoTC technology to provide frozen product to clinics worldwide. TC BioPharm also maintains a robust pipeline for future indications in solid tumors and other aggressive viral infections as well as a significant IP/patent portfolio in the use of CARs with gamma delta t-cells and owns our manufacturing facility to maintain cost and product quality controls.

Forward Looking StatementsThis press release may contain statements of a forward-looking nature relating to future events. These forward-looking statements are subject to the inherent uncertainties in predicting future results and conditions. These statements reflect our current beliefs, and a number of important factors could cause actual results to differ materially from those expressed in this press release. We undertake no obligation to revise or update any forward-looking statements, whether as a result of new information, future events or otherwise. The reference to the website of TC BioPharm has been provided as a convenience, and the information contained on such website is not incorporated by reference into this press release.

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SOURCE TC BioPharm

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TC BioPharm Announces Formation of Scientific Advisory Board with Renowned Cell Therapy Experts - GuruFocus.com

Global Adrenoleukodystrophy Treatment Market Trends, Growth, Opportunities and Forecast to 2029 Designer Women – Designer Women

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Theadrenoleukodystrophy treatment marketis expected to witness market growth at a rate of 10.25% in the forecast period of 2022 to 2029. Data Bridge Market Research report on adrenoleukodystrophy treatment market provides analysis and insights regarding the various factors expected to be prevalent throughout the forecast period while providing their impacts on the markets growth. The rise in the prevalence of chronic diseases globally is escalating the growth of adrenoleukodystrophy treatment market.

Adrenoleukodystrophy refers to a rare genetic condition that causes the buildup of long chain fatty acids (VLCFAs) in the brain. ALD is led by a mutation in the ABCD1 gene on the X chromosome. The three types of adrenoleukodystrophy including Adrenomyelopathy, Childhood cerebral ALD and Addisons disease. Childhood cerebral ALD is known to progress rapidly in children between the ages of 3 and 10.

Get Sample PDF of the Report https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-adrenoleukodystrophy-treatment-market

This adrenoleukodystrophy treatment market report provides details of new recent developments, trade regulations, import export analysis, production analysis, value chain optimization, market share, impact of domestic and localized market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, strategic market growth analysis, market size, category market growths, application niches and dominance, product approvals, product launches, geographic expansions, technological innovations in the market. To gain more info adrenoleukodystrophy treatment market contact Data Bridge Market Research for anAnalyst Brief, our team will help you take an informed market decision to achieve market growth.

Global Adrenoleukodystrophy Treatment Market Scope and Market Size

The adrenoleukodystrophy treatment market is segmented on the basis of types, treatment, route of administration, end-users and distribution channel. The growth among segments helps you analyze niche pockets of growth and strategies to approach the market and determine your core application areas and the difference in your target markets.

To get more insights into the market analysis, browse the research report summary @- https://www.databridgemarketresearch.com/reports/global-adrenoleukodystrophy-treatment-market

Adrenoleukodystrophy Treatment Market Country Level Analysis

The adrenoleukodystrophy treatment market is analyzed and market size information is provided by country, types, treatment, route of administration, end-users and distribution channel as referenced above. The countries covered in the global adrenoleukodystrophy treatment market report are U.S., Canada and Mexico in North America, Peru, Brazil, Argentina and Rest of South America as part of South America, Germany, Italy, U.K., France, Spain, Netherlands, Belgium, Switzerland, Turkey, Russia, Hungary, Lithuania, Austria, Ireland, Norway, Poland, Rest of Europe in Europe, Japan, China, India, South Korea, Australia, Singapore, Malaysia, Thailand, Indonesia, Philippines, Vietnam, Rest of Asia-Pacific (APAC) in Asia-Pacific (APAC), South Africa, Saudi Arabia, U.A.E, Kuwait, Israel, Egypt, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA).

North America dominates the adrenoleukodystrophy treatment market due to the well-established healthcare infrastructure and presence of key market players within the region. Asia-Pacific is expected to witness high growth during the forecast period of 2022 to 2029 because of the rise in awareness about rare diseases in the region.

The country section of the report also provides individual market impacting factors and changes in regulation in the market domestically that impacts the current and future trends of the market. Data points such as new sales, replacement sales, country demographics, disease epidemiology and import-export tariffs are some of the major pointers used to forecast the market scenario for individual countries. Also, presence and availability of global brands and their challenges faced due to large or scarce competition from local and domestic brands, impact of sales channels are considered while providing forecast analysis of the country data.

Competitive Landscape and Adrenoleukodystrophy Treatment Market Share Analysis

The adrenoleukodystrophy treatment market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, production capacities, company strengths and weaknesses, product launch, product width and breadth, application dominance. The above data points provided are only related to the companies focus related adrenoleukodystrophy treatment market.

Some of the major players operating in the adrenoleukodystrophy treatment market report are bluebird bio, Inc., Orpheris, Inc., MedDay Pharmaceuticals, MINORYX THERAPEUTICS SL, Pfizer Inc., Amgen Inc., AstraZeneca, Abbott, agtc, ReceptoPharm, Inc., The Myelin Project, SOM Biotech SL, Viking Therapeutics, Nutra Pharma Corporation, Genetix Biotech Asia Pvt. Ltd., Magenta Therapeutics, NeuroVia, Inc., Novartis AG, CELGENE CORPORATION, Jazz Pharmaceuticals, Inc., and Sanofi among others.

Browse Complete TOC athttps://www.databridgemarketresearch.com/toc/?dbmr=global-adrenoleukodystrophy-treatment-market

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Data Bridge Market Research has over 500 analysts working across different industries.We have served over 40% of Fortune 500 companies globally and have a network of over 5,000 clients worldwide.Data Bridge knows how to create satisfied customers who rely on our services and rely on our hard work with certainty.We are pleased with our glorious 99.9% customer satisfaction rating.

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Global Adrenoleukodystrophy Treatment Market Trends, Growth, Opportunities and Forecast to 2029 Designer Women - Designer Women

Litecoin Block Reward Halving Countdown

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Reward-Drop ETA date: 04 Aug 2023 19:05:03 UTC

As part of Litecoin's coin issuance, miners are rewarded a certain amount of litecoins whenever a block is produced (approximately every 2.5 minutes). When Litecoin first started, 50 litecoins per block were given as a reward to miners. After every 840,000 blocks are mined (approximately every 4 years), the blockreward halves and will keep on halving until the block reward per block becomes 0 (approximately by year 2142). As of now, the block reward is 12.5 coins per block and will decrease to6.25 coins per block post halving.

Litecoin was designed as a deflationary currency. Like gold, the premise is that over time, the issuance of litecoins will decrease and thus become scarcer over time. As litecoins become scarcer and if demand for them increases over time, Litecoin can be used as a hedge against inflation as the price, guided by price equilibrium is bound to increase. On the flip side, fiat currencies (like the US dollar), inflate over time as its monetary supply increases, leading to a decrease in purchasing power. This is known as monetary debasement by inflation. A simple example would beto compare housing prices decades ago to now and you'll notice that they've increased over time!

Since we know Litecoin's issuance over time, people can rely on programmed/controlled supply. This is helpful to understand what the current inflation rate of Litecoin is, what the future inflation rate will be at a specific point in time, how many litecoins are in circulation and how many remain left to be mined.

The network itself controls the issuance of litecoins, derived by consensus through all Litecoin participants. Ever since Litecoin was first designed, the following consensus rules exist to this day:

The first halving event occurred on the 25th of August, 2015 at block height 840,000.The second halving event occurred on the 5th of August, 2019 at block height 1,680,000.

It is always a debate on what Litecoin will do in terms of pricing for a halving event. Some people believe that the halving is already priced in by the market and thus there's no expectationfor the price to do anything. Others believe that due to price equilibrium, a halving of supply should cause an increase in price if demand for litecoins is equal or greater than what it was beforethe halving event. Below is a chart showing past price performance of the two halving events:

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Litecoin Block Reward Halving Countdown

Litecoin shoots up by 4620% – Not price, but… – AMBCrypto News

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One of the biggest disadvantages of Litecoin is its lack of demand, when compared to other altcoins in the market. At the same time, one of its biggest advantages also happens to be the lack of demand. That, in a weird way, is worth a milestone in itself.

Understandably, the silver to Bitcoins gold blew up on social media channels on the back of its achievement. In fact, its mentions increased by 4,620% within a matter of hours today.

This is the reason its lack of demand is an advantage since the rate of development on the blockchain is appropriate to its usage.

When either of the two factors exceeds or falls back, the network faces some sort of outage or downtime.

However, it isnt so that LTC has no demand at all. As one of the worlds most popular cryptos for payments, the altcoin is widely accepted. Just recently, for instance, it added Swiss luxury watchmaker Breitling to its list.

Worth pointing out, however, that these developments have meant zilch for LTCs price. The altcoin is still stuck in a downtrend, losing more than 15% of its value this week.Trading at $49 at press time, the crypto slipped back into the bearish zone, having barely escaped it after being stuck in it for almost three months.

At the moment, apart from utility, LTC isnt of much use for investors since it isnt bringing much profit to its holders. The return on investment over the last 12 months has declined significantly, with the same in the negatives right now.

Furthermore, only a few hundred thousand investors out of the millions that own LTC are still in profit. These investors bought their supply at a price lower than the alts current trading price. These investors make up just 13% of all LTC holders.

Given that Litecoins market value is also at its lowest in forever, it wouldnt be surprising if new investors refrain from putting their money into the asset. Even so, LTCs existing community will continue supporting it regardless.

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Litecoin shoots up by 4620% - Not price, but... - AMBCrypto News

Can Big Eyes (BIG), Litecoin (LTC), and Cardano (ADA) contribute to the internets transition into Web 3? – wknd.

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By Emily Milton

Published: Thu 7 Jul 2022, 4:54 PM

As blockchain technology continues to rapidly develop, the cryptocurrency ecosystem continues to expand and gather popularity. In a time in which the internet has a significant impact on the way we as a society communicate, create, interact and engage with one another, blockchain technology is looking to transition the internet into the iteration of web 3. This iteration describes the third generation of the evolution of web technologies. The likes of cryptocurrencies, NFTs, and decentralised finances (DeFi) being completely integrated into society thus replacing traditional centralised banking institutions.

This article will explore how three particular crypto tokens can help the transition of the internet into its new iteration.

Can BIG have an impact on crypto?

If there is one way to aid the transition into web 3, it is by being distinct and authentic, which is exactly what the community-driven coin BIG is. BIG stands out from other meme coins through its choice of mascot, which is a large-eyed cat designed in the popular Japanese computer-generated animation known as anime. This contrasts with the traditional branding of popular meme tokens such as Dogleon Mars, Shiba Inu, and Dogecoin which all characterise themselves as dog coins. With Big Eyes having an anime-style cat as their mascot, it instantly gives them a unique selling point, an area not significantly explored in the meme sector of crypto.

Moreover, Big Eyes is also a community-governed token that plans to protect a vital part of the worlds environment by transferring prosperity into the decentralised finance ecosystem. It wants to give more to crypto by building a blockchain ecosystem that self-propagates for hyper-growth. Itll do this using NFTs to offer access to more events and content that make the blockchain hype-ship worth boarding.

Additionally, BIG aims to give 5 per cent of its earnings to ocean-based charities an aspect that should entice people and aptly links to the theme of cats with their stereotypical enjoyment of fish. Big Eyes plans to have 90 per cent of its 200,000,000,000 tokens available at launch - conveying its increased availability to the average crypto buyer. An anti elitist stance is most welcome by most in the community.

The fast and secure network Litecoin (LTC)

If there is any crypto coin that can contribute to the gradual internet transition it is LTC, a blockchain network that is designed to provide users with secure, fast, and inexpensive payments by leveraging the unique properties of blockchain technology.

Essentially, LTC is a peer-to-peer cryptocurrency that is an open-source, global payment network that is fully decentralised without any focused authority.

LTC is the second most popular pure cryptocurrency behind Bitcoin due to its substantial industry support, liquidity and trade volume. Its primary features are improved storage efficiency and rapid transaction confirmation times. For these reasons, Litecoin has the potential to further elevate crypto since it enhances blockchain technology by exhibiting quick speed and cost-effectiveness.

The proof-of-stake network Cardano (ADA)

Cardano (ADA) is known for being a proof-of-stake cryptocurrency that aims to provide innovators, visionaries and changemakers to bring positive evolution internationally. The proof-of-stake consensus mechanism is used to create new blocks in blockchains and process transactions. Cardanos derivation is a 16th-century Italian polymath Gerolamo Cardano. It is also the first blockchain network to be founded on peer-reviewed research as well as being developed through evidence-based procedures.

Essentially, the ADA currency exists to redistribute control from unaccountable structures to the margins while propelling progress and positive change. With a current market capitalisation of $14,871,746,454 and ranking eighth on CoinMarketCap, Cardano has shown that it has the potential to advance the internet through its efficient blockchain technology.

More information on Big Eyes:

Website: http://www.bigeyes.space/

Telegram: //t.me/BIGEYESOFFICIAL

Emily Milton is the communications head at New Age Digital.

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Can Big Eyes (BIG), Litecoin (LTC), and Cardano (ADA) contribute to the internets transition into Web 3? - wknd.

How Gnox (GNOX) Could Potentially Allow You To Quit Your Day Job The Same Way Early Bitcoin (BTC) And Litecoin (LTC) Investors Did – The Coin Republic

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The vast majority of people getting involved in cryptos often have dreams of quitting their day job. After all, true financial freedom and the ability to just chill while you earn a living is the ultimate dream for nearly everyone. And with some cryptocurrencies in the past, most notably Bitcoin (and Litecoin), this dream has been more than realized for many. But if youre newer to crypto, you probably cant make retiring-early money from Bitcoin anymore. Even if prices do surge back up to something near all-time highs, youll still only be roughly doubling your money on current prices. Thats not retirement money. You need something thatll go bigger. Like those people who bought a thousand BTC when it was still only a few cents each. Now THATS quitting your day job money. So what options do you have? And how did people get rich with BTC and LTC? Lets have a look

The great thing about the Gnox protocol is that it gives you two ways to potentially quit your day job: price gains and long-term passive income. It isnt one or the other (unlike many other projects).

Gnox is up massively in just a few short weeks, at a time when the wider crypto market has seen huge losses. But this isnt a hedge, some analysts predict prices could surge even more if the wider market was in a healthier position. It has thrived despite market conditions, not because of them. And Gnox is still available in pre-sale at a discount, with more token burns planned to limit supply even more, the sky could be the limitand so could quitting your day job.

But its Gnoxs long-term passive income potential thats really got people talking. And GNOX investors are given an easy way to earn passive income, and potentially quit their day jobs, without many of the complications that are often associated with DeFi. Things like staking and liquidity pooling. Theyre hard to understand, and hard to manageespecially if youre new to crypto. And its things like that which put off newcomers to crypto rather than attract them. GNOX solves this issue with Yield Farming as a Service, a truly passive way to simply earn good yields from your holdings that anyone can enjoy, not just the tech-savvy or those well-versed in crypto.

Youve probably already heard some stories like this before, but theres a new generation of crypto millionaires thanks to BTC and to a lesser extent LTC. These coins saw massive gains, and those who got in early were more than able to quit their day jobs. But newcomers to crypto need new options for such gains, rather than simply relying on the established big coin. While BTC might pump back in price, it isnt going to see 100,000% gains like it once did.

You could still quit your day job if you invest in the right crypto. And many experts think GNOX could be that crypto.

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How Gnox (GNOX) Could Potentially Allow You To Quit Your Day Job The Same Way Early Bitcoin (BTC) And Litecoin (LTC) Investors Did - The Coin Republic

Elon Musk Reportedly Had Twins With a Company Exec Last Year – Rolling …

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Elon Musk is just doing his part to help populate Earth, according to his tweet following news that he secretly had twins with one of his companys executives last year. Doing my best to help the underpopulation crisis, he tweeted on Thursday, July 7. A collapsing birth rate is the biggest danger civilization faces by far. He added: Mark my words, they are sadly true.

Musk welcomed twins with Neuralinks Shivon Zilis in 2021, bringing his child tally up to nine known children, according to court documents obtained by Insider.

In April, the Tesla CEO and Zilis filed a petition to change the two childrens names to have their fathers last name and contain their mothers last name as part of their middle name, according to the outlet.

The two babies arrived just before he and Grimes had a child via surrogate in December. The mother of the twins currently works as director of operations and special projects for Neuralink, where Musk is co-CEO.

The news about the richest man alives two children comes days after his 18-year-old child Vivian Jenna Wilson was granted a name and gender change in California, removing Musk from her legal name and selecting a first name reflective of her gender identity.

Wilson told the court she wanted the name change due to the fact that I no longer live with or wish to be related to my biological father [Musk] in any way, shape or form, NBC reports.

Last month, the Tesla CEO was accused of exposing his penis to a flight attendant for SpaceX, his aerospace company, during a flight. The attendant was paid $250,000 to settle the case in 2018.

In March, Grimes revealed she had welcomed a second baby with Musk, named Exa Dark Siderl. They call her Y, following her older brother nicknamed X.

Asked byVanity Fair whether the two were still together, Grimes said at the time, Theres no real word for it I would probably refer to him as my boyfriend, but were very fluid. We live in separate houses. Were best friends. We see each other all the time We just have our own thing going on, and I dont expect other people to understand it.

Grimes added that they planned on having more kids as well. Weve always wanted at least three or four, she said.

She later sent out a series of tweets stating that the two had broken up, but that Musk was still the love of my life.

According toInsider, Musk and Amber Heard, who briefly dated in 2016, may also have frozen embryos together. During the Depp-Heard trial, the boss of Heards sister testified that she heard from Heards mother that the actress was in a legal battle with him over the rights to embryos they had created together. She added: He wanted to destroy them, and Amber tried to keep them to have a baby.

Perhaps Musks next mission isnt heading to space, but shooting babies out to singlehandedly change the United States fertility rate: After all, he has a chart of the countrys falling birth rate pinned to his Twitter profile. USA birth rate has been below min sustainable levels for ~50 years, reads the tweet.

This story was updated to include Elon Musks July 7 tweets about underpopulation.

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Elon Musk Reportedly Had Twins With a Company Exec Last Year - Rolling ...

Elon Musk – Biography – IMDb

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Overview (3) Mini Bio (1) Family (4) Trivia (19)

CEO & Product Architect of Tesla Motors and CEO & CTO SpaceX.

Co-founder, PayPal.

Chairman, Solar City.

Inducted into the International Space Hall of Fame in 2014.

Inducted into the Entrepreneur Hall of Fame.

8 books that he credits to his success are: 1.Structures: Or Why Things Don't Fall Down" by J.E. Gordon, 2. Benjamin Franklin: An American Life" by Walter Isaacson, 3. Einstein: His Life and Universe" by Walter Isaacson, 4. Superintelligence: Paths, Dangers, Strategies" by Nick Bostrom, 5. Merchants of Doubt" by Erik M. Conway and Naomi Oreskes, 6. Lord of the Flies" by William Golding, 7. Zero to One: Notes on Startups, or How to Build the Future" by Peter Thiel, 8. Foundation" trilogy by Isaac Asimov.

Read the entire Encyclopedia Britannica at age nine.

Read science fiction novels for more than 10 hours a day.

His SpaceX company made history, successfully completing the first commercial rocket launch from the NASA launch pad.[February 2017].

When asked if he believed religion and science could co-exist, Musk replied "Probably Not".

He does not pray or worship before rocket ship launch.

On April 2022, he bought the social platform Twitter, for the amount of 44 billion dollars.

The problem is that at a lot of big companies, process becomes a substitute for thinking. You're encouraged to behave like a little gear in a complex machine. Frankly, it allows you to keep people who aren't that smart, who aren't that creative.

I do love email. Wherever possible I try to communicate asynchronously. I'm really good at email.

Brand is just a perception, and perception will match reality over time. Sometimes it will be ahead, other times it will be behind. But brand is simply a collective impression some have about a product.

I think that's the single best piece of advice: constantly think about how you could be doing things better and questioning yourself.

I think it's very important to have a feedback loop, where you're constantly thinking about what you've done and how you could be doing it better.

The path to the CEO's office should not be through the CFO's office, and it should not be through the marketing department. It needs to be through engineering and design.

When something is important enough, you do it even if the odds are not in your favor.

I think it's very important to have a feedback loop, where you're constantly thinking about what you've done and how you could be doing it better. I think that's the single best piece of advice: constantly think about how you could be doing things better and questioning yourself.

If you go back back a few hundred years, what we take for granted today would seem like magic - being able to talk to people over long distances, to transmit images, flying, accessing vast amounts of data like an oracle. These are all things that would have been considered magic a few hundred years ago.

When Henry Ford made cheap, reliable cars people said, 'Nah, what's wrong with a horse?' That was a huge bet he made, and it worked.

I've actually made a prediction that within 30 years a majority of new cars made in the United States will be electric. And I don't mean hybrid, I mean fully electric.

I would like to die on Mars. Just not on impact.

If you're trying to create a company, it's like baking a cake. You have to have all the ingredients in the right proportion.

When I was in college, I wanted to be involved in things that would change the world.

There have only been about a half dozen genuinely important events in the four-billion-year saga of life on Earth: single-celled life, multicelled life, differentiation into plants and animals, movement of animals from water to land, and the advent of mammals and consciousness.

The reality is gas prices should be much more expensive then they are because we're not incorporating the true damage to the environment and the hidden costs of mining oil and transporting it to the U.S. Whenever you have an unpriced externality, you have a bit of a market failure, to the degree that externality remains unpriced.

Yeah, well I think anyone who likes fast cars will love the Tesla. And it has fantastic handling by the way. I mean this car will crush a Porsche on the track, just crush it. So if you like fast cars, you'll love this car. And then oh, by the way, it happens to be electric and it's twice the efficiency of a Prius.

I don't spend my time pontificating about high-concept things; I spend my time solving engineering and manufacturing problems.

Patience is a virtue, and I'm learning patience. It's a tough lesson.

It's OK to have your eggs in one basket as long as you control what happens to that basket.

Life is too short for long-term grudges.

The fuel cell is just a fundamentally inferior way of delivering electrical energy to an electric motor than batteries.

My background educationally is physics and economics, and I grew up in sort of an engineering environment - my father is an electromechanical engineer. And so there were lots of engineery things around me.

I've actually not read any books on time management.

We're running the most dangerous experiment in history right now, which is to see how much carbon dioxide the atmosphere... can handle before there is an environmental catastrophe.

I do think there is a lot of potential if you have a compelling product and people are willing to pay a premium for that. I think that is what Apple has shown. You can buy a much cheaper cell phone or laptop, but Apple's product is so much better than the alternative, and people are willing to pay that premium.

Really, the only thing that makes sense is to strive for greater collective enlightenment.

There are some important differences between me and Tony Stark, like I have five kids, so I spend more time going to Disneyland than parties.

I think life on Earth must be about more than just solving problems... It's got to be something inspiring, even if it is vicarious.

I think it matters whether someone has a good heart.

Silicon Valley has evolved a critical mass of engineers and venture capitalists and all the support structure - the law firms, the real estate, all that - that are all actually geared toward being accepting of startups.

It's obviously tricky to convert cellulose to a useful biofuel. I think actually the most efficient way to use cellulose is to burn it in a co-generation power plant. That will yield the most energy and that is something you can do today.

An asteroid or a supervolcano could certainly destroy us, but we also face risks the dinosaurs never saw: An engineered virus, nuclear war, inadvertent creation of a micro black hole, or some as-yet-unknown technology could spell the end of us.

My vision is for a fully reusable rocket transport system between Earth and Mars that is able to re-fuel on Mars - this is very important - so you don't have to carry the return fuel when you go there.

I really do encourage other manufacturers to bring electric cars to market. It's a good thing, and they need to bring it to market and keep iterating and improving and make better and better electric cars, and that's what going to result in humanity achieving a sustainable transport future. I wish it was growing faster than it is.

I tend to approach things from a physics framework. And physics teaches you to reason from first principles rather than by analogy.

Silicon Valley has some of the smartest engineers and technology business people in the world.

I feel very strongly that SpaceX would not have been able to get started, nor would we have made the progress that we have, without the help of NASA.

You could warm Mars up, over time, with greenhouse gases.

It would take six months to get to Mars if you go there slowly, with optimal energy cost. Then it would take eighteen months for the planets to realign. Then it would take six months to get back, though I can see getting the travel time down to three months pretty quickly if America has the will.

If humanity doesn't land on Mars in my lifetime, I would be very disappointed.

I would like to fly in space. Absolutely. That would be cool. I used to just do personally risky things, but now I've got kids and responsibilities, so I can't be my own test pilot. That wouldn't be a good idea. But I definitely want to fly as soon as it's a sensible thing to do.

Any product that needs a manual to work is broken.

The reason we should do a carbon tax is because it's the right thing to do. It's economics 101, elementary stuff.

America is the spirit of human exploration distilled.

The rumours of the demise of the U.S. manufacturing industry are greatly exaggerated.

It is definitely true that the fundamental enabling technology for electric cars is lithium-ion as a cell chemistry technology. In the absence of that, I don't think it's possible to make an electric car that is competitive with a gasoline car.

I think most of the important stuff on the Internet has been built. There will be continued innovation, for sure, but the great problems of the Internet have essentially been solved.

Automotive franchise laws were put in place decades ago to prevent a manufacturer from unfairly opening stores in direct competition with an existing franchise dealer that had already invested time, money and effort to open and promote their business.

I'm anti-tax, but I'm pro-carbon tax.

The odds of me coming into the rocket business, not knowing anything about rockets, not having ever built anything, I mean, I would have to be insane if I thought the odds were in my favor.

There's nothing - I've bought everything I want. I don't like yachts or anything; you know, I'm not a yacht person, and I've got pretty much the nicest plane I'd want to have.

For all the supporters of Tesla over the years, and it's been several years now and there have been some very tough times, I'd just like to say thank you very much. I deeply appreciate the support, particularly through the darkest times.

There are really two things that have to occur in order for a new technology to be affordable to the mass market. One is you need economies of scale. The other is you need to iterate on the design. You need to go through a few versions.

In the case of Apple, they did originally do production internally, but then along came unbelievably good outsourced manufacturing from companies like Foxconn. We don't have that in the rocket business. There's no Foxconn in the rocket business.

I was born in Africa. I came to California because it's really where new technologies can be brought to fruition, and I don't see a viable competitor.

I think the high-tech industry is used to developing new things very quickly. It's the Silicon Valley way of doing business: You either move very quickly and you work hard to improve your product technology, or you get destroyed by some other company.

You need to live in a dome initially, but over time you could terraform Mars to look like Earth and eventually walk around outside without anything on... So it's a fixer-upper of a planet.

Some people don't like change, but you need to embrace change if the alternative is disaster.

The future of humanity is going to bifurcate in two directions: Either it's going to become multiplanetary, or it's going to remain confined to one planet and eventually there's going to be an extinction event.

Facebook is quite entrenched and has a network effect. It's hard to break into a network once it's formed.

You need to be in the position where it is the cost of the fuel that actually matters and not the cost of building the rocket in the first place.

I just want to retire before I go senile because if I don't retire before I go senile, then I'll do more damage than good at that point.

People work better when they know what the goal is and why. It is important that people look forward to coming to work in the morning and enjoy working.

I wouldn't say I have a lack of fear. In fact, I'd like my fear emotion to be less because it's very distracting and fries my nervous system.

If anyone thinks they'd rather be in a different part of history, they're probably not a very good student of history. Life sucked in the old days. People knew very little, and you were likely to die at a young age of some horrible disease. You'd probably have no teeth by now. It would be particularly awful if you were a woman.

If anyone has a vested interest in space solar power, it would have to be me.

The space shuttle was often used as an example of why you shouldn't even attempt to make something reusable. But one failed experiment does not invalidate the greater goal. If that was the case, we'd never have had the light bulb.

I always invest my own money in the companies that I create. I don't believe in the whole thing of just using other people's money. I don't think that's right. I'm not going to ask other people to invest in something if I'm not prepared to do so myself.

I think there are more politicians in favor of electric cars than against. There are still some that are against, and I think the reasoning for that varies depending on the person, but in some cases, they just don't believe in climate change - they think oil will last forever.

The lessons of history would suggest that civilisations move in cycles. You can track that back quite far - the Babylonians, the Sumerians, followed by the Egyptians, the Romans, China. We're obviously in a very upward cycle right now, and hopefully that remains the case. But it may not.

Land on Mars, a round-trip ticket - half a million dollars. It can be done.

My opinion is it's a bridge too far to go to fully autonomous cars.

If we drive down the cost of transportation in space, we can do great things.

In order for us to have a future that's exciting and inspiring, it has to be one where we're a space-bearing civilization.

The United States is definitely ahead in culture of innovation. If someone wants to accomplish great things, there is no better place than the U.S.

As you heat the planet up, it's just like boiling a pot.

I've been to Disneyland, like, 10 times. I'm getting really tired of Disneyland.

I don't create companies for the sake of creating companies, but to get things done.

A Prius is not a true hybrid, really. The current Prius is, like, 2 percent electric. It's a gasoline car with slightly better mileage.

Physics is really figuring out how to discover new things that are counterintuitive, like quantum mechanics. It's really counterintuitive.

Great companies are built on great products.

Mars is the only place in the solar system where it's possible for life to become multi-planetarian.

I think long term you can see Tesla establishing factories in Europe, in other parts of the U.S. and in Asia.

I'm personally a moderate and a registered independent, so I'm not strongly Democratic or strongly Republican.

In order to have your voice be heard in Washington, you have to make some little contribution.

I'm glad to see that BMW is bringing an electric car to market. That's cool.

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Elon Musk - Biography - IMDb

A Guide to Elon Musks Many Children | Vanity Fair

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As you may have already heard against your will, Elon Musk has done more procreating. As Insider reports, he had twins with Shivon Zilis, the director of operations and special projects at his dystopian-lite brain implant company, Neuralink. The two children would bring his total to nine across three mothers.

What is he after? A baseball team? A full rocket ship to Mars and then also the first population of Mars? A cheer team that will win finals this year, so help me, God? A full kitchen in the brigade lineage? A nonet? Maybe none of the above. Hes said quite clearly in the past that intelligent people should procreate, and hes doing his part (are you itching to make the joke Im itching to make? Hehe).

Contrary to what many think, the richer someone is, the fewer kids they have, Musk said once on Twitter. I am a rare exception. Most people I know have zero or one kid.

Some may say its none of your business what the makeup of his three families are. Others may say, Please help me understand who these children are and who their mothers are and also the timeline on which he had these kiddos! To those I say, here is a short guide.

He had his first children with his first wife, Justine Musk, after they were married in 2000. Musk, whos an author, wrote an essay for Marie Claire in which she said he told her during their first dance at their wedding that he was the alpha in the relationship, and said that if she was his employee, he would fire her.

Whatever red flags might have arisen, they still had five children together, twins in 2004 and then triplets in 2006 (the couple had a child who died of sudden infant death syndrome at 10 weeks old, which she also writes about in the Marie Claire essay). One of the twins is named Griffin, and the triplets are Kai, Saxon, and Damian.

The other eldest twin, Vivian, 18, recently filed paperwork to change her first name, to reflect her gender, and her last name, to signal that she doesnt want to be related to my biological father in any way. Musk hasnt commented on his daughters request.

These kids have a special place in our hearts because in a Vanity Fair profile of Grimes, writer Devin Gordon discovered Grimes and Musks second child, their daughter Exa Dark Siderl Musk, when she made baby noises in her Austin home during an interview. Here is the explanation of her name, via Grimes:

Exa is a reference to the supercomputing term exaFLOPS (the ability to perform 1 quintillion floating-point operations per second). Dark, meanwhile, is the unknown. People fear it but truly its the absence of photons. Dark matter is the beautiful mystery of our universe. She texts me a voice memo with the pronunciation of Siderlsigh-deer-ee-elwhich she calls a more elven spelling of sidereal, the true time of the universe, star time, deep space time, not our relative earth time. Its also a nod to her favorite Lord of the Rings character, the powerful Galadriel, who chooses to abdicate the ring.

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A Guide to Elon Musks Many Children | Vanity Fair

Elon Musk secretly fathered twins with company exec last year, report says

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Bloomberg News,Bloomberg

July 7, 2022

FILE - Elon Musk speaks at the SATELLITE Conference and Exhibition March 9, 2020, in Washington.

(Bloomberg) -- Billionaire Elon Musk is the father of eight-month-old twins born to a senior executive at his artificial intelligence startup Neuralink, Insider reported, citing a court document.

Musk and the executive asked a Texas judge in April to change the childrens names to reflect both their surnames, Insider said. The request was granted, according to the report.

The two babies would bring Musks total known children to nine. He has advocated for increasing the population as part of his vision for colonizing other planets.

Neuralink, a closely held company controlled by Musk, and Musk didnt immediately respond to emailed inquiries, and Bloomberg couldnt immediately obtain a copy of the court document.

2022 Bloomberg L.P.

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Bloomberg News

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Elon Musk secretly fathered twins with company exec last year, report says

Elon Musk Reportedly Had Twins With One of His Executives

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Elon Musk and one of his top executives secretly had twins in November, according to a report Wednesday by Insider. The revelation came in court documents petitioning to have the children's last name changed to Musk.

The petition, signed by Musk, the CEO of both Tesla and SpaceX, and Shivon Zilis, director of operations and special projects at Musk's private neurotech startup, Neuralink, was approved by a judge in Austin, Texas, in May. The 36-year-old Zilis previously worked as project director in the CEO's office at Tesla.

The nature of their relationship wasn't immediately clear. Zilis formerly lived in San Francisco, but she bought a house in Austin about three months before the twins were born, Insider reported. The heavily redacted name-change petition lists that address for both Musk and Zilis, Insider reported.

Musk didn't immediately respond to a request for comment. Zilis couldn't immediately be reached for comment.

News that Musk, 51, had children with one of his direct reports comes less than two months after Insider reported that SpaceX had paid a flight attendant $250,000 to settle allegations that the billionaire exposed himself to her during a flight. Musk later denied the allegations, calling them "utterly untrue."

Musk, an outspoken advocate for population growth, now has nine children. Musk tweeted about declining birth rates in 2017, saying "The world's population is accelerating towards collapse, but few seem to notice or care."

In May, Musk tweeted a Wall Street Journal graphic tracking a "fertility slump" in the US since 1940.

"Contrary to what many think, the richer someone is, the fewer kids they have. I am a rare exception," Musk tweeted, adding later in the thread, "I mean, I'm doing my part haha."

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Elon Musk Reportedly Had Twins With One of His Executives

Elon Musk and girlfriend Natasha Bassett have lunch in St. Tropez

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Elon Musk and Natasha Bassett enjoyed a romantic getaway in St. Tropez over the weekend in celebration of Memorial Day.

The richest man in the world, 50, and the Australian actress, 27, were photographed having a leisurely lunch at the ritzy Cheval Blanc hotel Sunday afternoon.

The two were spotted gazing at nearby pool-goers and sunbathers as they sipped ros and shared a basket of French fries in the coastal town on the French Riviera.

Musk and Bassett sat close to each other and engaged in animated conversation throughout the meal. At one point, they were even seen belly-laughing as Musk made a grand gesture with his hands.

For the outdoor soire, the ever-casual Tesla CEO opted for a dark gray T-shirt, black jeans and matching boots.

Bassett kept her ensemble lighter and more colorful, sporting a patterned strapless sundress in a dark green hue, which she paired with strappy sandals.

Upon getting up from the table, the two held hands as they made their way out of the expensive eatery and onto the packed beach.

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"I want to show the world that were not submissive,...

One day prior, Musk and Bassett attended the star-studded wedding of Ari Emanuel who is said to have inspired the fictional Hollywood agent in Entourage and fashion designer Sarah Staudinger.

As Page Six previously reported, the affluent couples St. Tropez nuptials convenientlycoincided with the 2022 Cannes Film Festival, which concluded Saturday after an almost two-week run.

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"I want to show the world that were not submissive,...

Musk and Bassett attended multiple festival-related events together, including the premiere of the biographical musical drama Elvis.

In the biopic, which stars Austin Butler as the King of Rock n Roll, the Sydney native plays Elvis Presleys first girlfriend, Dixie Locke.

Musk and Bassett have been sparking romance rumors for a while now. A sourceclaimed to HollywoodLife in February the two had been dating for a couple of months and that they were already in a monogamous relationship.

Prior to Bassett, Musk was dating musician Grimes. The former couple share two kids: X A-Xii and Exa Dark Siderl.

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Elon Musk and girlfriend Natasha Bassett have lunch in St. Tropez

Elon Musk has new twins with Neuralink exec TechCrunch

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Last month, Insider published an explosive report about a former SpaceX flight attendant who accused SpaceX founder and CEO Elon Musk of propositioning her for sex in 2016 and to whom the company paid $250,000 to keep quiet. Musk called the story a politically motivated hit piece, while SpaceX president and COO Gwynne Shotwell came to Musks defense in a companywide email, writing: Personally, I believe the allegations to be false; not because I work for Elon, but because I have worked closely with him for 20 years and never seen nor heard anything resembling these allegations.

Alas, a new and far more damaging Insider report is putting Shotwell and every other executive insider Musks various companies in an even more uncomfortable position.

According to the story, court documents obtained by Insider show that the tech mogul Elon Musk quietly had twins last November with one of his top executives, Shivon Zilis. In April, Musk, 51, and Zilis, 36, filed a petition to change the twins names in order to have their fathers last name and contain their mothers last name as part of their middle name.'

The order was approved by a judge in Austin in May, adds the report, and the twins were born weeks before Musk and Claire Boucher, the musician who performs as Grimes, had their second child via surrogate in December.

Zilis is a Yale graduate who began her career at IBM, then invested on behalf of the Bloomberg-backed venture outfit Bloomberg Beta until early 2016 before moving on to OpenAI, then Tesla, then Neuralink.

All three, of course, have deep ties to Musk, who founded Neuralink, cofounded OpenAI and assumed leadership of Tesla back in 2008.

Specifically, says Insider, Zilis first met Musk in 2016 while a director at OpenAI, where she is now the youngest member on its board of directors. In 2017, she reportedly joined Tesla as a project director. Today, Zilis holds the title of director of operations and special projects for Neuralink, where Musk is a co-CEO.

Insider further reports that Zilis has recently been floated as one of the people Musk could tap to run Twitter if his proposed $44 billion acquisition of the company goes forward as expected.

Musk, who is typically highly active on Twitter, did not respond to requests for comment from Insider (neither did Zilis), though he last month tweeted that falling birth rates in the U.S. are a demographic disaster, adding, I mean, Im doing my part haha. [Update: Musk has since tweeted in response to the story: Doing my best to help the underpopulation crisis. A collapsing birth rate is the biggest danger civilization faces by far.]

The biggest question the story raises, beyond how many children Musk plans to father he has at least nine with various partners is whether any of these companies have fraternization policies that prohibit romantic relationships between a manager and a reporting staff member.

While most companies the size of Tesla and SpaceX prohibit dating relationships between employees who are separated by two levels in the chain of command, Musk is known for flouting traditional rules. (A Tesla employee handbook from 2020 isnt exactly standard fare, warning that Our assumption will be that if you dont call and dont show up for work, youre a jerk. You better have a really good reason for not letting us know why you didnt come in or youre out of here.)

Even if Neuralink, Tesla and OpenAI where Musk disassociated himself in 2019 do not have customary policies in place preventing fraternization, this new report is hugely problematic. Musk having secret children with a direct report will surely prove a huge distraction to other staffers. (You can imagine the water cooler conversation.) Its bad for morale, which is the last thing that Tesla in particular would seem to need right now given its many other employee battles. It could also open up Musks companies to massive lawsuits from Zilis if at some point down the road, she decides he abused the power he wielded as CEO.

Not last, though likely least concerning, the development will probably not be looked on kindly by the U.S. government, which has already been chilly toward Tesla under the Biden administration. (The government is a separately a large customer of SpaceX, where Zilis has not been an employee.)

We dont have anything against children, of course, but in running a business, not everything goes, and this newest development raises a lot of questions about the boards of directors at Musks companies. It also puts execs like Shotwell in the position of having to reassure employees that Musk has the same good judgment, self-control and laser-like focus on his companies success as he says he expects of them. We dont envy her the job.

[Update/correction: The original version of our story reported that a LinkedIn page for Zilis appeared to have been taken offline, but its now available to view here.]

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Elon Musk reportedly fathered twins with executive at one of his …

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FILE - Tesla CEO Elon Musk attends the opening of the Tesla factory Berlin Brandenburg in Gruenheide, Germany, on March 22, 2022.

Elon Musk, the Tesla and SpaceX CEO and world's richest man, welcomed twins last year with an executive at one of his other companies, Neuralink, Business Insiderreportedon Wednesday.

Musk, who posted atweeton May 24 saying "USA birth rate has been below min sustainable levels for ~50 years" and pinned it to the top of his more than 100 million-follower Twitter account, quietly fathered the children with Shivon Zilis, who works for Musk at the company which hopes to develop an implantable computer chip for the human brain, according to documents obtained by Business Insider.

Keep scrolling for photos of Elon Musk through the years

The outlet obtained court filings pertaining to changing the children's legal names to incorporate the Musk last name, and Zilis' as part of the middle names. CNN Business could not independently confirm the contents of the documents, but a Travis County, Texas court docket obtained by CNN Business indicated that the name change petition was initially filed in April 2022 and granted in early May matching the dates on the documents published by Business Insider. Those documents contain the court's stamp as well as Musk's signature, listing him as the father and Zilis as the mother.

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Musk did not immediately respond to requests for comment sent to representatives at Tesla, SpaceX and Neuralink.

Zilis' professional ties to Musk date back to at least April 2016, according to herLinkedIn profile, when she became an advisor to OpenAI. Musk is one of thecofoundersof OpenAI, a nonprofit research laboratory with a stated mission to "ensure that artificial general intelligence benefits all of humanity."

In August 2020, Musk held alive-streamed eventintended to showcase the progress of Neuralink's technology, which it had implanted in a pig. Nearly a year later, Neuralinkclaimed monkeyscould play Pong after the company's chips were inserted into their brains. But, more recently, Neuralink has had to address concerns about its testing practices, denying allegations of animal cruelty while confirming earlier this year that monkeys have died as part of the testing.

According to Zilis' LinkedIn, she worked for both Tesla and Neuralink beginning in May 2017; and currently works as a director of operations and special projects at Neuralink. In 2020, Zilis became a board member at OpenAI. Prior to working at Musk-helmed companies, Zilis worked for a Bloomberg venture capital fund (whichlanded heron the Forbes 30 under 30 list for venture capital in 2015), as well as IBM. She's also served on the boards of at least two other artificial intelligence-related organizations. Zilis did not immediately respond to a request for comment.

This is the second set of twins Musk is currently believed to have fathered. Musk and his first wife, Justine, had twins in 2004 before welcoming triplets two years later. (The two, who were married from 2000 to 2008, lost their first child; Justine, an author, famously wrote about what it was like to be married to, and divorce, Musk forMarie Claire magazinein 2010.) Musk subsequently had two children with musician Claire Boucher, who is better known as Grimes. Theirsecond child was bornin December 2021 through a surrogate.

FILE - In this Oct. 20, 2000 file photo, PayPal Chief Executive Officer Peter Thiel, left, and founder Elon Musk, right, pose with the PayPal logo at corporate headquarters in Palo Alto, Calif. (AP Photo/Paul Sakuma, File)

FILE - In this Dec. 9, 2008 file photo, Tesla Motors CEO Elon Musk stands in front a Tesla sports car at a Tesla showroom in Menlo Park, Calif. (AP Photo/Paul Sakuma, file)

FILE - In this March 26, 2009 file photo, Tesla Motors CEO, Chairman and Product Architect Elon Musk speaks at the unveiling of the Tesla Model S all-electric 5-door sedan, in Hawthorne, Calif., Thursday, March 26, 2009. (AP Photo/Reed Saxon, File)

In this July 21, 2009 photo, shows Tesla CEO Elon Musk talking about the lawsuit at Tesla headquarters in San Carlos, Calif., Tuesday, July 21, 2009. (AP Photo/Paul Sakuma)

In this Tuesday, July 21, 2009 photo, Tesla CEO Elon Musk poses at Tesla headquarters in San Carlos, Calif. (AP Photo/Paul Sakuma)

President Barack Obama walks to look at the Flacon 9 launch vehicle with SpaceX CEO Elon Musk at Kennedy Space Center Thursday, April 15, 2010.(AP Photo/Alex Brandon)

Calif. Gov., Arnold Schwarzenegger, right, Toyota CEO Akio Toyoda, left, and Tesla CEO Elon Musk, center, at Tesla headquarters in Palo Alto, Calif., Thursday, May 20, 2010. Tesla and Toyota officials announce partnership. (AP Photo/Paul Sakuma)

Elon Musk, CEO of Tesla Motors, poses with a Tesla car in front of Nasdaq following the electric automakers initial public offering, Tuesday, June, 29, 2010, in New York. The company plans to trade on the Nasdaq stock exchange under the ticker "TSLA." (AP Photo/Mark Lennihan)

Elon Musk, center, CEO of Tesla Motors, raises his hand at the Nasdaq opening bell to celebrate the electric automakers initial public offering, Tuesday, June, 29, 2010 in New York. (AP Photo/Mark Lennihan)

Elon Musk, co-founder, chief executive and product architect of Tesla Motors, poses at the premiere of the documentary film "Revenge of the Electric Car," Friday, Oct. 21, 2011, at Tesla Motors in Los Angeles. The film is director Chris Paine's follow-up to his 2006 documentary, "Who Killed the Electric Car?" (AP Photo/Chris Pizzello)

SpaceX CEO and Chief Designer Elon Musk walks in a procession after delivering the commencement speech for Caltech graduates in Pasadena, Calif. Friday, June 15, 2012. (AP Photo/Damian Dovarganes)

SpaceX CEO Elon Musk gives the opening keynote at the SXSW Interactive Festival on Saturday, March 9, 2013 in Austin, Texas. (AP Photo/Jack Plunkett)

FILE - In this May 29, 2014 file photo, Elon Musk, CEO and CTO of SpaceX, introduces the SpaceX Dragon V2 spaceship at the SpaceX headquarters in Hawthorne, Calif. (AP Photo/Jae C. Hong, File)

Elon Musk, CEO of Tesla Motors Inc., introduces the Model X car at the company's headquarters Tuesday, Sept. 29, 2015, in Fremont, Calif. Musk said the Model X sets a new bar for automotive engineering, with unique features like rear falcon-wing doors, which open upward, and a driver's door that opens on approach and closes itself when the driver is inside. (AP Photo/Marcio Jose Sanchez)

Elon Musk, CEO & Chief Product Architect of Tesla Moters, attends the premiere of "Racing Extinction" during the 2015 Sundance Film Festival on Saturday, Jan. 24, 2015, in Park City, Utah. (Photo by Arthur Mola/Invision/AP)

SpaceX founder Elon Musk speaks during the 67th International Astronautical Congress in Guadalajara, Mexico, Tuesday, Sept. 27, 2016. In a receptive audience full of space buffs, Musk said he envisions 1,000 passenger ships flying en masse to Mars, 'Battlestar Galactica' style. He calls it the Mars Colonial fleet, and he says it could become reality within a century. Musk's goal is to establish a full-fledged city on Mars and thereby make humans a multi-planetary species. (AP Photo/Refugio Ruiz)

President Donald Trump talks with Tesla and SpaceX CEO Elon Musk, center, and White House chief strategist Steve Bannon during a meeting with business leaders in the State Dining Room of the White House in Washington, Friday, Feb. 3, 2017. (AP Photo/Evan Vucci)

Grimes, left, and Elon Musk attend The Metropolitan Museum of Art's Costume Institute benefit gala celebrating the opening of the Heavenly Bodies: Fashion and the Catholic Imagination exhibition on Monday, May 7, 2018, in New York. (Photo by Charles Sykes/Invision/AP)

SpaceX founder and chief executive Elon Musk speaks after announcing Japanese billionaire Yusaku Maezawa as the first private passenger on a trip around the moon, Monday, Sept. 17, 2018, in Hawthorne, Calif. (AP Photo/Chris Carlson)

Elon Musk, co-founder and chief executive officer of Tesla Inc., speaks during an unveiling event for the Boring Co. Hawthorne test tunnel in Hawthorne, Calif., on Tuesday, Dec. 18, 2018. Musk has unveiled his underground transportation tunnel, allowing invited guests to take some of the first rides ever on the tech entrepreneur's solution to "soul-destroying traffic." (Robyn Beck/Pool Photo via AP)

Tesla CEO Elon Musk jokingly motions to kick before introducing the Model Y at Tesla's design studio Thursday, March 14, 2019, in Hawthorne, Calif. The Model Y may be Tesla's most important product yet as it attempts to expand into the mainstream and generate enough cash to repay massive debts that threaten to topple the Palo Alto, Calif., company. (AP Photo/Jae C. Hong)

NASA Administrator Jim Bridenstine, left, talks with SpaceX chief engineer Elon Musk, second from left, and NASA astronauts crew Doug Hurley and Bob Behnken, right, in front of the Crew Dragon spacecraft, about the progress to fly astronauts to and from the International Space Station, from American soil, as part of the agency's commercial crew program at SpaceX headquarters, in Hawthorne, Calif., Thursday, Oct. 10, 2019. (AP Photo/Alex Gallardo)

Tesla CEO Elon Musk introduces the Cybertruck at Tesla's design studio Thursday, Nov. 21, 2019, in Hawthorne, Calif. Musk is taking on the workhorse heavy pickup truck market with his latest electric vehicle. (AP Photo/Ringo H.W. Chiu)

Elon Musk, founder, CEO, and chief engineer/designer of SpaceX speaks during a news conference after a Falcon 9 SpaceX rocket test flight to demonstrate the capsule's emergency escape system at the Kennedy Space Center in Cape Canaveral, Fla., Sunday, Jan. 19, 2020. (AP Photo/John Raoux)

Tesla and SpaceX Chief Executive Officer Elon Musk speaks during a round table discussion with President Donald Trump at Kennedy Space Center, Wednesday, May 27, 2020, in Cape Canaveral, Fla. (AP Photo/Evan Vucci)

Tesla and SpaceX Chief Executive Officer Elon Musk jumps in the air as people applaud during an event at the Vehicle Assembly Building on Saturday, May 23, 2020, at NASA's Kennedy Space Center in Cape Canaveral, Fla. The event occurred after a rocket ship designed and built by SpaceX lifted off on Saturday with two Americans on a history-making flight to the International Space Station. NASA Administrator Jim Bridenstine looks on at left. (AP Photo/Alex Brandon)

SpaceX owner and Tesla CEO Elon Musk arrives on the red carpet for the Axel Springer media award, in Berlin, Germany, Tuesday, Dec. 1, 2020. (Hannibal Hanschke/Pool via AP)

Elon Musk walks from the justice center in Wilmington, Del., Monday, July 12, 2021. Musk took to a witness stand Monday to defend his company's 2016 acquisition of a troubled company called SolarCity against a shareholder lawsuit that claims he's to blame for a deal that was rife with conflicts of interest and never delivered the profits he had promised. (AP Photo/Matt Rourke)

Elon Musk, Tesla CEO, attends the opening of the Tesla factory Berlin Brandenburg in Gruenheide, Germany, Tuesday, March 22, 2022. The first European factory in Gruenheide, designed for 500,000 vehicles per year, is an important pillar of Tesla's future strategy. (Patrick Pleul/Pool via AP)

-- CNN's Rachel Metz contributed reporting

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Originally posted here:

Elon Musk reportedly fathered twins with executive at one of his ...