CytoDyn’s Phase 2 Study of Leronlimab for Mild-to-Moderate COVID-19 Selected for Oral Presentation at the Special isirv-AVG Virtual Conference on…

VANCOUVER, Washington, Sept. 22, 2020 (GLOBE NEWSWIRE) CytoDyn Inc. (OTC.QB: CYDY), (CytoDyn or the Company), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today the Phase 2 study of leronlimab for mild-to-moderate COVID-19 patients has been selected for an oral presentation at the upcoming Special isirv-Antiviral Group Conference on Therapeutics for COVID-19. The Conference is sponsored by the International Society for Influenza and other Respiratory Virus Diseases, an independent and international scientific professional society promoting the prevention, detection, treatment, and control of influenza and other respiratory virus disease.

Details of the presentation are as follows:

Abstract Title:A Phase 2 Study of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19). Abstract Confirmation Number:AAVGV0010 Presenter:Harish Seethamraju, M.D., Medical Director, Advanced Lung Failure and Lung Transplant, Montefiore Medical Center, Bronx, New York. Presentation Date and Time:October 6-8, 2020 12.00-4.00pm GMT and will be available on demand.

Additional details can be found on the conference web sitehere

The acceptance of this oral abstract by this highly regarded scientific organization is very rewarding for all of the medical professionals who provided care and treatment to the COVID-19 patients during our Phase 2 trial. We also view this acceptance as a validation of leronlimab as a potential therapeutic for this disease and we look forward to the upcoming interim analysis from our Phase 3 trial for severe-to-critical COVID-19 patients, said Nader Pourhassan, Ph.D., President and Chief Executive Officer of CytoDyn.

About Coronavirus Disease 2019 CytoDyn completed its Phase 2 clinical trial (CD10) for COVID-19, a double-blinded, randomized clinical trial for mild-to-moderate patients in the U.S. which produced statistically significant results for NEWS2. Enrollment continues in its Phase 3 randomized clinical trial for the severe-to-critically ill COVID-19 population in several hospitals throughout the U.S.; an interim analysis on the first 195 patients will be announced by mid-October.

About Leronlimab (PRO 140) The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for critical illnesses. The first indication is a combination therapy with HAART for HIV-infected patients and the second is for metastatic triple-negative breast cancer. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH.Leronlimab has completed nine clinical trials in over 800 people and met its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).

In the setting of HIV/AIDS, leronlimab is a viral-entry inhibitor; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab has been the subject of nine clinical trials, each of which demonstrated that leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn is, therefore, conducting a Phase 1b/2 human clinical trial in metastatic triple-negative breast cancer and was granted Fast Track designation in May 2019.

The CCR5 receptor appears to play a central role in modulating immune cell trafficking to sites of inflammation. It may be crucial in the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others further support the concept that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells.CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to support further the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD, blocking the CCR5 receptor from recognizing specific immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of GvHD.

About CytoDyn CytoDyn is a late-stage biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a critical role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and immune-mediated illnesses, such as GvHD and NASH.

CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients. The FDA met telephonically with Company key personnel and its clinical research organization and provided written responses to the Companys questions concerning its recent Biologics License Application (BLA) for this HIV combination therapy in order to expedite the resubmission of its BLA filing for this indication.

CytoDyn has completed a Phase 3 investigative trial with leronlimab as a once-weekly monotherapy for HIV-infected patients. CytoDyn plans to initiate a registration-directed study of leronlimab monotherapy indication. If successful, it could support a label extension. Clinical results to date from multiple trials have shown that leronlimab can significantly reduce viral burden in people infected with HIV. No drug-related serious site injection reactions reported in about 800 patients treated with leronlimab and no drug-related SAEs reported in patients treated with 700 mg dose of leronlimab. Moreover, a Phase 2b clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients; some patients on leronlimab monotherapy have remained virally suppressed for more than six years.

CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and a Phase 1b/2 clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is atwww.cytodyn.com.

Forward-Looking Statements This press release contains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. Forward-looking statements specifically include statements about leronlimab, its ability to have positive health outcomes, the possible results of clinical trials, studies or other programs or ability to continue those programs, the ability to obtain regulatory approval for commercial sales, and the market for actual commercial sales. The Companys forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i) the sufficiency of the Companys cash position, (ii) the Companys ability to raise additional capital to fund its operations, (iii) the Companys ability to meet its debt obligations, if any, (iv) the Companys ability to enter into partnership or licensing arrangements with third parties, (v) the Companys ability to identify patients to enroll in its clinical trials in a timely fashion, (vi) the Companys ability to achieve approval of a marketable product, (vii) the design, implementation and conduct of the Companys clinical trials, (viii) the results of the Companys clinical trials, including the possibility of unfavorable clinical trial results, (ix) the market for, and marketability of, any product that is approved, (x) the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companys products, (xi) regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii) general economic and business conditions, (xiii) changes in foreign, political, and social conditions, and (xiv) various other matters, many of which are beyond the Companys control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form 10-K, and any risk factors or cautionary statements included in any subsequent Form 10-Q or Form 8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CYTODYN CONTACTS Investors: Michael Mulholland Office: 360.980.8524, ext. 102 mmulholland@cytodyn.com

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CytoDyn's Phase 2 Study of Leronlimab for Mild-to-Moderate COVID-19 Selected for Oral Presentation at the Special isirv-AVG Virtual Conference on...

Advances in the Treatment of Mantle Cell Lymphoma are Greatly Improving the Long-Term Outlook for Patients – Curetoday.com

When James Landon received a mantle cell lymphoma (MCL) diagnosis in 2017, he was told his disease was indolent, meaning it was slow growing and didnt need to be treated right away, especially since he was feeling fine.

But that changed in 2019. Landon, 50, an attorney in Tucson, Arizona, started to feel tired all the time. His physicians discovered that his white blood cell count was sky-high and his spleen was enlarged.

The first-line treatment for MCL has long been high doses of chemotherapy, often followed by a stem cell transplant. But when Landon traveled to The University of Texas MD Anderson Cancer Center in Houston to explore his options, he was offered an alternative: an experimental regimen combining the drugs Imbruvica (ibrutinib) and Rituxan (rituximab). Imbruvica blocks a protein called Bruton tyrosine kinase (BTK), which is a driver of MCL, and Rituxan is an antibody that targets overactive B cells of the immune system that have been implicated in the disease.

Five months after starting the combination four Imbruvica pills every morning and once-weekly infusions of Rituxan Landons positron emission tomography (PET) scan showed no evidence of disease. If he stays clear, hell undergo a short course of chemotherapy and then move to a maintenance therapy of one year of Ibrutinib and two of Rituxan.

Having this option has been fantastic, in my opinion, because the drugs so far have worked well for me, with no toxicity, says Landon, who adds that he has plenty of energy to work full time and play with his 10-year-old son.

BTK inhibitors and immunotherapy are among the newer therapeutic options for patients with MCL that are greatly improving the outlook for long-term survival. In addition to these targeted drugs, Tecartus (brexucabtagene autoleucel) the first cell-based gene therapy for MCL in patients who havent responded to or who have relapsed following other kinds of treatment was approved by the Food and Drug Administration (FDA) in July and is a one-time personalized treatment made from patients own immune cells.

We now have several good nonchemotherapy options for treating MCL, says Dr. Anthony Nguyen, a professor at the University of Nevada, Las Vegas School of Medicine and a medical oncologist at Comprehensive Cancer Centers of Nevada. We may be able to tell patients we can treat them without toxic chemotherapy, which can be reassuring, particularly for older patients.

MCL is a subtype of non-Hodgkin lymphoma (NHL) thats characterized by the overproduction of a protein called cyclin D1. In about 85% of patients, that overproduction is caused by a genetic abnormality called reciprocal chromosomal translocation, which can be detected with diagnostic testing of tumor samples. MCL accounts for about 6% of all NHL diagnoses and is more common in men than in women, according to the Leukemia & Lymphoma Society.

The standard first-line treatment for MCL is high-dose chemotherapy, often with a four-medicine regimen called hyper-CVAD, followed by a stem cell transplant with a patients own cells or with those from a donor. The regimen often puts patients into long-term remissions, but the side effects including nausea, mouth ulcers and kidney damage can be difficult or even dangerous, particularly for patients with other illnesses.

The newer medicines and cell therapy were approved by the FDA to treat patients with MCL who dont respond to chemotherapy and transplants or who relapse. But as physicians gain more experience with these therapies, theres a growing interest in using them earlier in the treatment process to not only improve the chances of long-term remissions, but also to improve the quality of life for patients by sparing them from harsh side effects.

The FDA approved the first BTK inhibitor to treat MCL, Imbruvica, in 2013, based on a study showing an overall response rate (meaning the disease responded to treatment) of 68% and a complete response rate (the disappearance of all signs of cancer) of 21%. The average period that patients lived without their disease progressing was more than a year, and side effects were mild stomach upset and fatigue.

The more recently approved BTK inhibitors Calquence (acalabrutinib) and Brukinsa (zanubrutinib) have improved on those response rates. Patients receiving Brukinsa in a late-stage trial, for example, had an overall response rate of 89% and a complete response rate of 59%.

Another targeted treatment, Venclexta (venetoclax) is also being studied in MCL. Venclexta targets the protein BCL2, which promotes cell survival and is abnormally elevated in MCL helping to drive progression of the disease. In a small trial of Venclexta, 75% of patients with relapsed MCL responded to the drug, 21% of whom had complete responses. Theres even more interest in studying BCL2 inhibition in combination with BTK blockers. In a recent study of Venclexta combined with Imbruvica, the median progression-free survival time was 29 months.

This is an extremely promising combination, says Dr. Abhijeet Kumar, assistant professor in the division of hematology and oncology at the University of Arizona College of Medicine. Kumar is an investigator in an ongoing trial of Venclexta and Imbruvica in MCL.

There is, however, a risk of increased side effects when targeted treatments are combined. Imbruvica can cause bleeding, for example, and both drugs can lower neutrophil (a type of white blood cell) counts. Venclexta is also known to cause tumor lysis syndrome, a rapid release of tumor cells into the bloodstream that can endanger the kidneys and other organs. Still, so far, the combination seems to be well-tolerated, Kumar says.

Another two-drug treatment for MCL that has generated enthusiasm among oncologists treating the disease is dubbed R-squared because it combines Rituxan with Revlimid (lenalidomide), a drug that works by boosting the immune systems T cells and natural killer cells, which work together to attack cancer.

In a study of R-squared in 38 patients with newly diagnosed MCL, the progression-free survival rate after three years was 80% and overall survival reached 90%. The response is durable, says Dr. Bijal Shah, an associate member in the department of malignant hematology at Moffitt Cancer Center and one of the study investigators. During the R-squared trial, patients typically stayed on the combination for three years and then took Revlimid alone as long as the disease remained stable.

Similar benefits have been seen with a combination of Velcade (bortezomib), Revlimid and chemotherapy, a regimen called VR-CAP. Velcade is a targeted drug that works by disrupting the growth of MCL cells and prompting them to die.

In a trial of patients with untreated MCL, adding Velcade to Revlimid and chemotherapy extended progression-free survival by 37%. The addition of Velcade more than doubled the median duration of response to 41 months.

Both R-squared and VR-CAP have moved into the frontline treatment setting, Shah says. With that, were able to see really pronounced clinical benefits. Weve seen very long remissions, he says.

Several other combination strategies also are being investigated for MCL, including some that incorporate the drug Treanda (bendamustine), which works by causing DNA damage to cancer cells. In one study, combining Treanda with Rituxan improved progression-free survival rates over chemotherapy in patients with MCL or indolent NHL. More than 15 studies are now underway combining Treanda with Rituxan and other MCL treatments.

Even though targeted and combination treatments have extended survival times in MCL, most patients eventually relapse. Now theres a new option for those patients: Tecartus, a personalized therapy made from a patients own immune cells. The one-time treatment was approved by the FDA to treat patients who have not responded or have relapsed following other kinds of treatment.

Tecartus is a chimeric antigen receptor (CAR)-T cell therapy similar to Yescarta (axicabtagene ciloleucel), a CAR-T cell therapy approved by the FDA in 2017 to treat some types of large B-cell lymphomas. Like Yescarta, Tecartus targets CD19, a protein thats prevalent in cancerous B cells. Tecartus is made by extracting T cells from the blood of the patient with MCL and genetically modifying those cells to recognize and attack the cancer. In addition, the cells are put through an enrichment process designed to prevent them from wearing down before they are infused back into the patient.

In the clinical trial that led up to the approval, 87% of patients responded to Tecartus and 62% went into remission. Side effects, which included the immune overreaction known as cytokine release syndrome and neurological events, were manageable during the clinical trial, says Dr. Michael Wang, a professor in the department of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center and one of the clinical trial investigators.

Experience with previously approved CAR-T cell treatments led to the widespread use of anti-inflammatory medications such as interleuken-6 inhibitors and steroids to treat cytokine release syndrome, Wang says. We have a variety of supportive measures to manage the side effects, he says.

With the approval of Tecartus, Wang says oncologists can envision a flattening of the survival curve in MCL. Its an option for people who become resistant to targeted therapies and chemotherapy, he says. Its very possible we will be able to put some people into long- term remissions.

Bob Brixner, a 20-year survivor of MCL, has been watching all the new developments with interest. When he received an MCL diagnosis in 2000, he had no choice but to endure chemotherapy followed by a stem cell transplant with his own cells. When he relapsed in 2004, he was prescribed a more intense chemotherapy regimen, followed by a stem cell transplant from an unrelated donor.

Hes grateful the second treatment put him in a long-term remission, but he still remembers the brutal side effects, which included extreme fatigue and a bout with pneumonia. And with the transplants, my immune system didnt come back 100%, says Brixner, 70, a retired Chicago public schoolteacher. Nowadays if I catch a cold, instead of lasting a week, it will last three.

Brixner advises all newly diagnosed patients to ask a lot of questions about their treatment choices and to get a second opinion. I think its really important to be an informed patient, he says, especially since there are so many new choices. Some patients may not have to go through what I did, he says. Im delighted.

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Advances in the Treatment of Mantle Cell Lymphoma are Greatly Improving the Long-Term Outlook for Patients - Curetoday.com

Opdivo (nivolumab) Demonstrated Superior Disease-Free Survival in Patients with Resected Esophageal or Gastroesophageal Junction Cancer Compared to…

Details Category: Antibodies Published on Tuesday, 22 September 2020 10:41 Hits: 601

Adjuvant Opdivo doubled disease-free survival; is the first therapeutic option to show statistically significant and clinically meaningful disease-free survival benefit in these patients, regardless of tumor histology, following chemoradiation therapy and resection

Results from Phase 3 CheckMate -577 trial selected for presentation during a Presidential Symposium at the European Society for Medical Oncology Virtual Congress 2020

PRINCETON, NJ, USA I September 21, 2020 I Bristol Myers Squibb (NYSE: BMY) today announced first results from the Phase 3 CheckMate -577 trial in which adjuvant treatment with Opdivo (nivolumab) showed a statistically significant and clinically meaningful improvement in disease-free survival (DFS), the trials primary endpoint, compared to placebo in patients with esophageal or gastroesophageal junction (GEJ) cancer following neoadjuvant chemoradiation therapy (CRT) and tumor resection. The current standard of care for patients with esophageal or GEJ cancer following neoadjuvant CRT and tumor resection is surveillance. These results signify the first time an adjuvant therapeutic option has significantly prolonged DFS for patients in this setting.

Median DFS was doubled in patients receiving Opdivo [22.4 months; (95% Confidence Interval [CI]: 16.6 to 34.0)] compared to those receiving placebo after surgery [11.0 months; (95% CI: 8.3 to 14.3)] (Hazard Ratio [HR] 0.69; 96.4% CI: 0.56 to 0.86; p=0.0003). The median duration of treatment for patients in the Opdivo arm was just over 10 months [10.1 months (<0.1 to 14.2)] versus nine months for patients in the placebo arm [9.0 months (<0.1 to 15)]. The safety profile of Opdivo in CheckMate -577 was consistent with previously reported studies of Opdivo monotherapy.

While about 25% to 30% of patients with esophageal or gastroesophageal junction cancer achieve a complete response following chemoradiation therapy and surgery, the remaining 70% to 75% do not, and there is currently no adjuvant treatment option available for these patients with the potential to improve their outcomes, said Ronan J. Kelly M.D., MBA, Director, Charles A. Sammons Cancer Center at Baylor University Medical Center. Adjuvant treatment with nivolumab in the CheckMate -577 trial doubled patients time without disease recurrence, representing the first adjuvant treatment advancement for these patients with esophageal or gastroesophageal junction cancer.

Opdivo was well tolerated with an acceptable safety profile relative to placebo. The majority of patients in the Opdivo arm (89%) were able to receive a relative dose intensity of 90%. The incidence of any treatment-related adverse events (TRAEs), including any grade and Grade 3-4, was 71% and 13% among patients treated with Opdivo compared to 46% and 6% among patients receiving placebo. Serious TRAEs of any grade and Grade 3-4 occurred in less than 10% of patients treated with Opdivo (any grade in 8%, Grade 3-4 in 5%) compared to 3% and 1% of patients receiving placebo, with a low rate of any grade treatment-related discontinuations in both arms (9% for Opdivo vs. 3% in placebo).

These results make esophageal and gastroesophageal junction cancer the second cancer type following melanoma where Opdivo has demonstrated a benefit in the adjuvant setting, indicating the potential for Opdivo to become a new standard of care for these patients, said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol Myers Squibb. This advancement showcases our commitment to evaluating our therapies in earlier stages of disease where we may be able to have a greater impact on preventing disease recurrence and improving patient outcomes. We look forward to discussing these encouraging results from CheckMate -577 with global health authorities in the coming months.

These data (Presentation #LBA9) will be featured in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 on September 21 from 19:31-19:43 CEST.

About CheckMate -577

CheckMate -577 is a Phase 3 randomized, multi-center, double-blind study evaluating Opdivo as an adjuvant therapy in patients with resected esophageal or GEJ cancer who have received neoadjuvant CRT therapy and have not achieved a pathological complete response. The primary endpoint of the trial is DFS and the secondary endpoint is overall survival (OS). Following neoadjuvant CRT therapy and complete tumor surgical resection (also known as trimodality therapy), a total of 794 patients were randomized to receive placebo (n=262) or Opdivo (n=532) 240 mg by intravenous infusion every two weeks for 16 weeks followed by Opdivo 480 mg every four weeks until disease recurrence, unacceptable toxicity or withdrawal of consent, with a maximum of one year total treatment duration.

About Esophageal Cancer

Esophageal cancer is the seventh most common cancer and the sixth leading cause of death from cancer worldwide, with approximately 572,000 new cases and over 508,000 deaths in 2018. The two most common types of esophageal cancer are squamous cell carcinoma and adenocarcinoma, which account for approximately 85% and 15% of all esophageal cancers, respectively, though esophageal tumor histology can vary by region with the highest rate of esophageal adenocarcinoma occurring in North America (65%). The majority of cases are diagnosed in the advanced setting and impact a patients daily life, including their ability to eat and drink.

About Gastric Cancer

Gastric cancer, also known as stomach cancer, is the fifth most common cancer and the third leading cause of cancer death worldwide, with over 1,000,000 new cases and approximately 783,000 deaths in 2018. There are several cancers that can be classified as gastric cancer, including certain types of cancers that form in the GEJ, the area of the digestive tract where the esophagus and stomach connect. While GEJ cancer has a lower prevalence than gastric cancer, it continues to rise.

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational CAR T cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early- to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering potential new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the bodys own immune system to help restore anti-tumor immune response. By harnessing the bodys own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivos leading global development program is based on Bristol Myers Squibbs scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Companys Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

INDICATIONS

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with intermediate or poor risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

CheckMate Trials and Patient Populations

Checkmate 037previously treated metastatic melanoma; Checkmate 066previously untreated metastatic melanoma; Checkmate 067previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LApreviously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 017second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 032small cell lung cancer; Checkmate 025previously treated renal cell carcinoma; Checkmate 214previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039classical Hodgkin lymphoma; Checkmate 141recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275urothelial carcinoma; Checkmate 142MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040hepatocellular carcinoma, as a single agent or in combination with YERVOY; Checkmate 238adjuvant treatment of melanoma; Attraction-3esophageal squamous cell carcinoma

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens for patients with cancer in Japan, South Korea and Taiwan.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.

SOURCE: Bristol-Myers Squibb

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Opdivo (nivolumab) Demonstrated Superior Disease-Free Survival in Patients with Resected Esophageal or Gastroesophageal Junction Cancer Compared to...

Coronavirus Researchers Discover How COVID-19 May Trigger Fatal Levels of Lung Inflammation – SciTechDaily

CT scan of patients lungs showing COVID-19 damage in red. Credit: Gerlig Widmann and team, Department of Radiology, Medical University of Innsbruck

Responding to the COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2, requires models that can duplicate disease development in humans, identify potential targets and enable drug testing. Specifically, access to primary human lung in vitro model systems is a priority since a variety of respiratory epithelial cells are the proposed targets of viral entry.

Now, a team of infectious disease, pulmonary and regenerative medicine researchers at Boston University, studying human stem cell-derived lung cells called type 2 pneumocytes, infected with SARS-CoV-2, have shown that the virus initially suppresses the lung cells ability to call in the help of the immune system with interferons to fight off the viral invaders and instead activates an inflammatory pathway called NFkB. The infected lung cells pour out inflammatory proteins. In the body of an infected person, those proteins drive up levels of inflammation in the lungs, explains corresponding author Darrell Kotton, MD, the David C. Seldin Professor of Medicine at BUSM and Director of the BU/BMC Center for Regenerative Medicine (CReM).

According to the researchers, the inflammatory signals initiated by the infected pneumocytes attract an army of immune cells into lung tissue laden with infected and already dead and dying cells. Our data confirms that SARS-CoV-2 blocks cells from activating one of the anti-viral branches of the immune system early on after infection has set in. The signal the cells would typically send out, a tiny protein called interferon that they exude under threat of disease, are instead delayed for several days, giving SARS-CoV-2 plenty of time to spread and kill cells, triggering a buildup of dead cell debris and other inflammation, added Kotton.

The data is based on experiments the research team performed in the laboratory of co-senior author Elke Mhlberger, PhD, associate professor of microbiology at BUSM and a researcher at BUs National Emerging Infectious Diseases Laboratories (NEIDL). Kotton and other members of the CReM have developed sophisticated models of human lung tissuethree-dimensional structures of lung cells, called lung organoids, grown from human stem cellswhich theyve used at BU and with collaborators elsewhere to study a range of chronic and acute lung diseases.

The research team, led by co-first authors, Jessie Huang, PhD, Kristy Abo, BA, Rhiannon Werder, PhD and Adam Hume, PhD, adapted an experimental model previously used to study the effects of smoking cigarettes to study the coronavirus in lung tissue. Droplets of live coronavirus were then added on top of the lung cells, infecting them from the air the way the virus infects cells lining the inside of the lungs when air containing the virus is breathed into the body. This adaptation of human stem cell-derived pneumocytes to air, known as an air-liquid interface cell culture was a key advance that allowed us to simulate how SARS-CoV-2 enters cells deep in the lungs of the most severely affected patients, said co-senior author Andrew Wilson, MD, associate professor of medicine at BUSM. Type 2 pneumocytes are also infected and injured in patients with COVID-19, making this a clinically meaningful system to understand how the disease injures patient lungs.

Wilson and Kotton, are also pulmonary and critical care physicians taking care of patients with COVID-19 pneumonia at Boston Medical Center, while also leading their laboratories to produce the human lung cells that were then transported into the NEIDL. There Hume, a senior research scientist in the Mhlbergers lab, worked in a BSL-4 suit to perform the infections of the cells that the three collaborating teams then analyzed together through weekly zoom calls.

These cells are an amazing platform to study SARS-CoV-2 infection, adds Mhlberger. They likely reflect what is going on in the lung cells of COVID-19 patients. If you look at the damage SARS-CoV-2 inflicts on these cells, you definitely dont want to get the disease.

These findings appear online in the journal Cell Stem Cell.

Reference: SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response by Jessie Huang, Adam J. Hume, Kristine M. Abo, Rhiannon B. Werder, Carlos Villacorta-Martin, Konstantinos-Dionysios Alysandratos, Mary Lou Beermann, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Judith Olejnik, Ellen L. Suder, Esther Bullitt, Anne Hinds, Arjun Sharma, Markus Bosmann, Ruobing Wang, Finn Hawkins, Eric J. Burks, Mohsan Saeed, Andrew A. Wilson, Elke Mhlberger and Darrell N. Kotton, 18 September 2020, Cell Stem Cell. DOI: 10.1016/j.stem.2020.09.013

Funding for this study was provided by Evergrande MassCPR awards, the National Institutes of Health, a CJ Martin Early Career Fellowship from the Australian National Health and Medical Research Council, an I. M. Rosenzweig Junior Investigator Award from the Pulmonary Fibrosis Foundation, a Harry Shwachman Cystic Fibrosis Clinical Investigator Award, the Gilead Sciences Research Scholars Program, Gilda and Alfred Slifka and Gail and Adam Slifka funds, a Cystic Fibrosis Foundation grant, and a Fast Grants award.

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Coronavirus Researchers Discover How COVID-19 May Trigger Fatal Levels of Lung Inflammation - SciTechDaily

City of Hope Enters Licensing Agreement With Chimeric to Develop Its Pioneering Chlorotoxin CAR T Cell Therapy – Business Wire

DUARTE, Calif.--(BUSINESS WIRE)--City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, today announced that it has licensed intellectual property relating to its pioneering chlorotoxin chimeric antigen receptor (CLTX-CAR) T cell therapy to Chimeric Therapeutics Limited, an Australian biotechnology company.

The therapy is currently being used in a phase 1 clinical trial at City of Hope to treat glioblastoma (GBM), a type of brain tumor. The first patient in the trial was recently dosed; Behnam Badie, M.D., chief of City of Hopes Division of Neurosurgery and The Heritage Provider Network Professor in Gene Therapy, is leading this innovative, first-of-its-kind trial.

Chimeric has acquired the exclusive worldwide rights to develop and commercialize certain patents relating to City of Hopes CLTX-CAR T cells, as well as to further develop the therapy for other cancers.

City of Hope is excited to enter into this agreement with Chimeric as it supports our innovative research in CAR T cell therapy and our commitment to extend these therapies to more patients, particularly those with GBM and other solid tumors that are difficult to treat, said Christine Brown, Ph.D., The Heritage Provider Network Professor in Immunotherapy and deputy director of City of Hopes T Cell Therapeutics Research Laboratory. Chimeric shares our goal of providing effective CAR T cell therapies to more patients with current unmet medical needs.

Led by Brown and Michael Barish, Ph.D., chair of City of Hopes Department of Developmental and Stem Cell Biology, and Dongrui Wang, Ph.D., a recent graduate of City of Hopes Irell & Manella Graduate School of Biological Sciences, the team developed and tested the first CAR T cell therapy using CLTX, a component of scorpion venom, to direct T cells to target brain tumor cells. The research was published this past March in Science Translational Medicine.

Chimeric is excited to join City of Hope in its quest to find more effective cancer therapies. This is an exceedingly rare opportunity to acquire a promising technology in one of the most exciting areas of immuno-oncology today, said Paul Hopper, executive chairman of Chimeric. Furthermore, the CLTX-CAR T cell therapy has completed years of preclinical research and development, and recently enrolled its first patient in a phase 1 clinical trial for brain cancer.

CARs commonly incorporate a monoclonal antibody sequence in their targeting domain, enabling CAR T cells to recognize antigens and kill tumor cells. In contrast, the CLTX-CAR uses a synthetic 36-amino acid peptide sequence first isolated from death stalker scorpion venom and now engineered to serve as the CAR recognition domain.

In this recent study, City of Hope researchers used tumor cells in resection samples from a cohort of patients with GBM to compare CLTX binding with expression of antigens currently under investigation as CAR T cell targets. They found that CLTX bound to a greater proportion of patient tumors, and cells within these tumors.

CLTX binding included the GBM stem-like cells thought to seed tumor recurrence. Consistent with these observations, CLTX-CAR T cells recognized and killed broad populations of GBM cells while ignoring nontumor cells in the brain and other organs. The study team demonstrated that CLTX-directed CAR T cells are highly effective at selectively killing human GBM cells without off-tumor targeting and toxicity in cell-based assays and in animal models.

City of Hope, a recognized leader in CAR T cell therapies for GBM and other cancers, has treated more than 500 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world it currently has 30 ongoing CAR T cell clinical trials, including CAR T cell trials for HER-2 positive breast cancer that has spread to the brain, and PSCA-positive bone metastatic prostate cancer. It was the first and only cancer center to treat GBM patients with CAR T cells targeting IL13R2, and the first to administer CAR T cell therapy locally in the brain, either by direct injection at the tumor site, through intraventricular infusion into the cerebrospinal fluid, or both. In late 2019, City of Hope opened a first-in-human clinical trial for patients with recurrent GBM, combining IL13R2-CAR T cells with checkpoint inhibitors nivolumab, an anti-PD1 antibody, and ipilimumab, blocking the CTLA-4 protein.

Both an academic medical center and a drug development powerhouse, City of Hope is known for creating the technology used in the development of human synthetic insulin and numerous breakthrough cancer drugs. Its unique research and development hybrid of the academic and commercial creates an infrastructure that enables City of Hope researchers to submit an average of 50 investigational new drug applications to the U.S. Food and Drug Administration each year. The institution currently holds more than 450 patent families.

"City of Hope is delighted to license this technology to Chimeric, said Sangeeta Bardhan Cook, Ph.D., City of Hope director of the Office of Technology Licensing. We are impressed with the ability of their executive team to push and bring therapies to market expeditiously. At City of Hope, our mission is to transform the future of health care. We believe Chimeric has the vision to offer innovative therapies to cancer patients.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nations Best Hospitals in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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City of Hope Enters Licensing Agreement With Chimeric to Develop Its Pioneering Chlorotoxin CAR T Cell Therapy - Business Wire

The Holistic Sanctuary Announces Exciting Plans to Expand Over Next 4 Years and Save More Lives – PRNewswire

BEVERLY HILLS, Calif., Sept. 19, 2020 /PRNewswire/ -- The Holistic Sanctuary is proud to announce its exciting plans to grow the number of cutting-edge luxury centers it has over the next four years, allowing it to help even more patients in need of its pioneering treatments.

After a decade of revolutionizing the holistic health field and saving lives, The Holistic Sanctuary, which currently has a state-of-the-art facility in Baja California (Mexico), plans to open another center in Tulum, Mexico, as well as an additional three centers in several other locations around the world.

Holistic Sanctuary Tulum is well on its way to opening its doors in 2021, which will be followed by plans to open other centers in Tulum (2021), Malibu (2022), London (2023) and Dubai (2024).

The Holistic Sanctuary is a world-class holistic medical spa that uses cutting-edge technology and advanced therapies from around the world to cure, heal, and reverse illnesses and diseases that Western medical professionals have said are incurable. By using a combination of natural therapies, they help people to recover from a variety of different conditions such as depression, addiction, PTSD, stress, anxiety, and more.

Johnny Tabaie, CEO and Founder of The Holistic Sanctuary, said:"We are incredibly excited that we will soon be able to help even more patients around the world. We've taken holistic healing to a whole different level, and our intention has always been to heal patients using natural, effective, holistic and other alternative therapies that give results in real-time, without having to medicate people with addictive drugs.

"We simplytransform people's lives; we give them a fighting chance at a good quality oflife. We get people off prescribed medications, heal the underlying cause of PTSD, depression, trauma and even addiction, then send them back home healthy, thriving, happy and whole again."

More information on The Holistic Sanctuary's luxury drug rehab centers can be found at https://www.theholisticsanctuary.com/luxury-rehab-centers/

In addition to its growth plans, the organization has also announced that by the end of 2020 it will have the first AIDS and cancer research center that will strive to cure diseases like this using revolutionary stem cell technology. It will also be able to treat other autoimmune conditions such as lupus, rheumatoid arthritis, Lyme disease, neuropathy, multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).

This kind of cutting technology has been around for the last 30 years, revolutionizing how illnesses like these are treated through the discovery of isolated stem cell genes that have been proven clinically to showit has cured two patients suffering from AIDS and cancer. One has been clear for 10 years now, with the other being cured last year. This is a new, paradigm-shifting approach that is pushing western medication treatment to the side.

To learn about how stem cell technology is used by the centers, more information can be found here: https://www.theholisticsanctuary.com/stem-cell-therapy/

Learn more about The Holistic Sanctuary's Mexico stem cell center here: https://www.theholisticsanctuary.com/stem-cell-therapy/mexico/

The Holistic Sanctuary has an 80% success rate at healing patients that are either on medications, alcohol, street drugs, or suffer from mental health disorders such as PTSD, depression, anxiety and trauma. See more information on what treatments are used for these:

"We've incorporated holistic medicine and methodically weaved it with sacred plant medicine to have a better synergistic never before seen outcome. In the last 10 years, we have therapeutically, safely and humanely given people sacred plant medicines like Ibogaine, DMT, Changa, 5-MEO, Kambo, Psilocybin, mushrooms, and much more,"added Tabaie.

The organization is looking for investors and partners to help finance and push this revolutionary vision forward. For more information about The Holistic Sanctuary and investor relations, please send an email or call +1-310-601-7805 or visit their website at http://www.theholisticsanctuary.com.

About The Holistic Sanctuary

The Holistic Sanctuary is a world-class holistic medical spa that uses cutting-edge and advanced therapies from around the world. It uses powerful modalities to cure, heal, and reverse illnesses and diseases that Western medical professionals have said are incurable. It is not a drug rehab, more along the lines of a luxury treatment center that transforms lives. It helps people to recover from depression, any type of addiction, PTSD, stress, anxiety, as well as other mental health problems. The centers use a combination of natural therapies to help people recover mentally, physically and emotionally. Unlike mainstream doctors, rehabs, and treatment centers, The Holistic Sanctuary avoids the use of outdated theories, ineffective therapies and addiction to toxic medications and drugs. Instead, it addresses the root causes of these illnesses, improves physical and mental health and alleviates the illnesses.

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Company Name: The Holistic Sanctuary

Contact Person: Investor Relations

Email: [emailprotected]

Phone: +1-310-601-7805

Address: 1212 Wilshire Blvd.

City:Beverly Hills

State:California

Website: http://www.theholisticsanctuary.com

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Robert E. Windsor, MD, is being recognized by Continental Who’s Who – PRNewswire

ALPHARETTA,Ga., Sept. 21, 2020 /PRNewswire/ --Robert E. Windsor, MD, is being recognized by Continental Who's Who as a Distinguished Leader for his remarkable contributions in the field of Medicine and for his dedication and commitment as the President, Medical Director, and Regenerative Medicine Specialist at Georgia RegenRX.

Located in the greater Atlanta area at 5755 North Point Pkwy, Suite #72, Alpharetta, Georgia, Georgia RegenRX offers expert, caring pain management and regenerative medical services to the Atlanta metropolitan area. Dr. Windsor plans to expand his practice into all aspects of regenerative medicine to include aesthetics and life extension. He believes that people do not need to age physiologically nearly as rapidly as they traditionally have and that they should remain mentally and physically vital and continue to look good while they age. An acclaimed physician, he has helped thousands of patients recover from the pain and improve their quality of life.

Backed by more than three decades of experience, Dr. Windsor is a top physician in Fulton County and will be expanding his practice into Forsyth and Gwinnett counties in 2021. His areas of expertise include interventional pain medicine, interventional orthopedics, regenerative medicine (e.g., stem cell therapy), integrative medicine, longevity medicine, and pain management for arthritis, chronic spinal pain, and sports injuries. In addition to his administrative and clinical experience, he has held numerous faculty positions. He has been a Pain Management Fellowship Director at Emory University, a leader at the American Academy of Physical Medicine, and a Visiting Professor at the University of Pennsylvania and Temple University among others.

Pursuing a pain/rehabilitative/physical medicine career to help others, Dr. Windsor always keeps, "the patient first and foremost." He has been highly successful because he continues to learn and develops new and improved skill sets. He advises new doctors to, "Stay up to date on emerging technologies in the biological field (i.e.: Stem cells)". He loves his field, remaining in his career for so many years because of his fervor for improving the function and quality of life of injured, ill, and/or elderly people.

In preparation for his career, Dr. Windsor earned a medical degree from the Texas A&M University College of Medicine at the age of twenty-three. He went on to complete a competitive residency program in physical medicine and rehabilitation at the University of Texas Health Sciences Center at San Antonio. Then, he earned board certification in Physical Medicine, Electrodiagnostic Medicine, Pain Medicine, Pain Management, Age Management Medicine, and Regenerative Medicine and he is currently completing a fellowship in Aesthetic Medicine.

A frontrunner in his field, Dr. Windsor has been board certified by the American Board of Physical Medicine, American Board of Pain Medicine, American Board of Pain Management, American Board of Electrodiagnostic Medicine, American Board of Age Management Medicine, and the American Board of Regenerative Medicine. In appreciation of his service, Dr. Windsor was honored as America's Top Physician by the Consumers Research Council of America in 2014. The President of PASSOR, he has received the following PASSOR awards: Distinguished Clinician, Distinguished Committee, and Distinguished Member. He has been active in his field throughout his career, having previously served as the past-Executive Board Member of the AAPM&R.

A lifelong athlete, Dr. Windsor enjoys staying active. He likes lifting weights, snow skiing, scuba diving, boating, and skydiving. He is heavily involved with his family. He has many offspring, several of whom are engaged in the medical field.

Dr. Windsor dedicates this recognition to Stanley Herring, MD, Richard Derby, MD, Charles April, MD, and Daniel Dumitru, MD, Ph.D. For more information, please visit https://www.garegenrx.com

Contact: Katherine Green, 516-825-5634 [emailprotected]

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Emerging immunotherapies in multiple myeloma – The BMJ

Immunotherapies that are currently being studied in multiple myeloma are discussed in this section under four headings: checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody drug conjugates (fig 2).

Malignant plasma cells in most patients with multiple myeloma express the checkpoint programmed death-ligand 1, which is upregulated especially when exposed to inflammatory mediators such as interferon . Interaction of this checkpoint molecule with programmed cell death protein 1 on T cells limits their proliferation and cytotoxic activity.6869

The first study evaluating single agent nivolumab for relapsed multiple myeloma showed a response in only one of 27 patients.7071 Despite a lack of single agent activity, single arm trials combining checkpoint inhibitors with immunomodulatory imide drugs and dexamethasone because of the potential synergy72 look promising.7374

With these clinical data, three large randomized phase III trials were halted by the FDA in 2017 because of increased serious adverse events and deaths as well as decreased overall survival in the checkpoint inhibitor arm (pomalidomide and dexamethasone with and without pembrolizumab) in relapsed and refractory multiple myeloma (hazard ratio 1.61, 95% confidence interval 0.91 to 2.85),75 pomalidomide and dexamethasone with and without nivolumab in relapsed and refractory multiple myeloma (1.19, 0.64 to 2.20),76 and lenalidomide and dexamethasone with and without pembrolizumab in transplant ineligible patients with newly diagnosed multiple myeloma (2.06, 0.93 to 4.55)77).

These trials encourage caution with expedited timelines for future combination studies for drugs with limited single agent activity.7879 Future trials in multiple myeloma will need to be based on sound preclinical and clinical rationale with other partners and be conducted in heavily treated patients (with limited standard options) initially.

CAR T cells are human T cells that have been genetically modified and expanded in the laboratory before they are infused back into patients to target the tumor. The receptor on the surface of CAR T cells that targets the tumor antigens consists of several parts (fig 3): an extracellular, non-major histocompatibility complex restricted, targeting domain, usually derived from a single chain variable fragment of a monoclonal antibody; a spacer region; a transmembrane domain; an intracellular signaling domain including the CD3 activation domain; and a costimulatory domain (eg, CD28 or 4-1BB). The single chain variable fragment was originally derived from mice (hence the term chimeric), but many of the newer constructs are fully human.8081

Chimeric antigen receptor (CAR) T cell structure

CD3 positive T cells are obtained from patients (for autologous CAR T cells) or healthy donors (for allogeneic CAR T cells) via a process called leukapheresis. These T cells are expanded manifold in culture and activated using beads coated with anti-CD3 or anti-CD28 monoclonal antibodies or cell based artificial antigen presenting cells.82 The T cells are then transduced with a vector (usually either lentiviral or retroviral) that carries the gene encoding a receptor to an antigen present on the surface of tumor cells. This manufacturing process takes up to four weeks at a good manufacturing practices facility, and the CAR T cells can then be stored until needed by the patient. This delay means that the disease must not be rapidly progressing, so that the patient is able to wait until the CAR T product is ready; otherwise the patient will need bridging chemotherapy. Two to seven days before CAR T cell infusion, a patient receives lymphodepleting chemotherapy to make way for the CAR T cells that are subsequently given as an intravenous infusion. Once infused into patients, the CAR T cells encounter the antigen, proliferate, and kill the tumor cells (fig 4). These cells, therefore, combine the target specificity of a monoclonal antibody with the enhanced cytotoxicity of T cells without requiring human leucocyte antigen presentation of the target antigen.83

Chimeric antigen receptor (CAR) T cell treatment for multiple myelomasequence of events. CRS=cytokine release syndrome; ICANS=immune effector cell associated neurotoxicity syndrome

An ideal antigen is one that is widely and exclusively expressed on cancer cells but not on normal cells to enhance efficacy and reduce toxicity.8485 In multiple myeloma, most emerging immunotherapies (including CAR T cells) target B cell maturation antigen (BCMA), a type III transmembrane receptor, which is a promising target antigen.8687 BCMA is also known as tumor necrosis factor receptor superfamily member 17 or CD269. It is expressed in nearly all plasma cells (normal and malignant) although its expression is variable.88 BCMA promotes plasma cell survival and is induced during plasma cell differentiation89 by binding to ligands (a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF)) that are produced by osteoclasts.90 Increased levels of soluble BCMA are associated with high tumor burden in multiple myeloma and thus worse outcomes.91

CAR T cells targeting CD19 were approved by the FDA in 2017 for refractory large B cell lymphoma9293 and acute lymphoblastic leukemia,94 and are being used in clinical practice. The first study on CAR T cell treatment directed by BCMA opened in 2014 at the US National Cancer Institute.879596 Since then, about a dozen of different early phase clinical trials have been conducted on BCMA CAR T treatment for advanced multiple myeloma.9798 A detailed review outlining the differences in the construct, manufacturing, and clinical efficacy of these different products has been published previously.8186

This review focuses on four BCMA CAR T cell products that are currently being evaluated in registration (that is, for regulatory approval) phase I/II clinical trials for patients with relapsed and refractory multiple myeloma. These products include bb2121 (now known as idecabtagene vicleucel or ide-cel), JCARH125 (now known as orvacabtagene autoleucel or orva-cel), LCAR-B38M (now known as JNJ-4528), and P-Bcma-101. FDA approvals for some of these agents are anticipated in 2020-21 for relapsed and refractory multiple myeloma (fig 5; table 2). The high overall response rates of 60-100% seen in these trials in a highly refractory population is unprecedented, although the durability of these responses is still in question.

Four major constructs of chimeric antigen receptor (CAR) T cells targeting B cell maturation antigens (BCMA), currently in multicenter clinical trials investigating multiple myeloma. This figure does not include all BCMA constructs in multiple myeloma. ScFv=single chain variable fragment; VH only=variable-heavy chain only fragments

Summary of major multicenter clinical trials investigating multiple myeloma treatments*

The most advanced CAR T cell treatment targeting a BCMA is ide-cel (bb2121), which uses a lentiviral vector for CAR insertion and includes a 4-1BB costimulatory domain as well as a murine single chain variable fragment.114 In a phase I non-randomized, open label, multicenter trial in relapsed and refractory multiple myeloma (3 prior lines of treatment) for 33 patients treated at various doses,115 researchers found an overall response rate of 85% with a median progression free survival of 11.8 months. A higher overall response rate was seen at the higher dose levels and doses of 150-450106 CAR T cells were defined as the active dose.115 This dose is being tested currently in a multicenter, single arm, open label trial to evaluate bb2121 CAR T cells further in relapsed and refractory multiple myeloma; the trial has completed enrolment of 149 patients worldwide. Preliminary results show an overall response rate of 73% (complete response rate 33%) and median progression free survival of 8.8 months in 128 patients treated at doses of 150-450106 cells (table 2).99 Fifty four patients treated at the highest dose level of 450106 cells had an overall response rate of 82% and a median progression free survival of 12.1 months.99 These results have been submitted to regulatory agencies including the FDA and European Medicines Agency for treatment for advanced multiple myeloma.

Orva-cel (JCARH125) is another second generation CAR product with a fully human B cell derived single chain variable fragment, a 4-1BB costimulatory domain, and optimized manufacturing (predefined CD4:CD8 ratio) that is derived from preclinical work at Memorial Sloan Kettering Cancer Center. The preliminary data for the multicenter phase I/II EVOLVE study were presented at the American Society of Clinical Oncology meeting in 2020. These patients had received a median of six prior treatments. They received escalating doses of 50-600106 cells. The results for 62 patients treated at the 300-600106 cells dose range showed an overall response rate of 92% (complete response rate 36%).100101 The trial is currently enrolling at the recommended phase II dose of 600106 cells (table 2).

The LCAR-B38M CAR construct was developed initially in China and is currently being pursued in the US and globally as JNJ-4528 (table 2). It consists of two llama derived variable-heavy chain only fragments that target two epitopes of BCMA designed to confer avidity. In a phase I/II study in China, researchers found deep durable responses with a median progression free survival of 19.9 months and a manageable safety profile in relapsed and refractory multiple myeloma, although the patients in this study were treated earlier in their disease course with a median of three prior lines of treatment and were therefore less heavily pre-treated.102103104105 In the US and Europe, a multicenter phase Ib/II clinical trial of this CAR construct as JNJ-4528 in relapsed and refractory multiple myeloma (3 prior lines of treatment) was conducted to confirm the findings of the LEGEND-2 study. Preliminary results of the phase Ib portion showed an overall response rate of 100% (complete response rate 86%) in patients with a median of five prior lines of treatment (table 2).106107 The phase II portion is fully enrolled, and phase II and III studies have been initiated.

P-BCMA-101 is uniquely manufactured using the non-viral piggyBac gene editing system, which is less costly, produces cells with a high percentage of favorable stem cell memory phenotype T cells, and has the ability to include a safety switch. The binding molecule for this product is not a single chain variable fragment but a small fully human fibronectin domain (Centyrin) that has higher specificity and potentially less immunogenicity. In a phase I dose escalation trial, the overall response rate was 63% with a median progression free survival of 9.5 months in 19 evaluable patients108 (table 2).

CAR T cell treatments have a unique toxicity profile where patients can develop side effects such as cytokine release syndrome and neurotoxicity that has been recently termed immune effector cell associated neurotoxicity syndrome (ICANS).116 Cytokine release syndrome has been defined as a disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, or hypoxia caused by the release of cytokines from cells. The American Society for Transplantation and Cellular Therapy has developed a consensus grading system for cytokine release syndrome, which depends on the severity and presence of fever, hypotension, or hypoxia (table 3).116

American Society for Transplantation and Cellular Therapy consensus grading for cytokine release syndrome (CRS)116

ICANS has been defined as a disorder involving the central nervous system following any immunotherapy that results in the activation or engagement of endogenous or infused T cells or other immune effector cells. Symptoms or signs can be progressive and could include aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral edema.116 It includes four grades that are determined by the ICE score (immune effector cell associated encephalopathy score, which provides objectivity to grading encephalopathy), level of consciousness, seizure, motor findings, and elevated intracranial pressure or cerebral edema (table 4).116 Management of ICANS and cytokine release syndrome is based on grading and involves supportive care, steroids, and interleukin blocking agents.117118 Interleukin 6 blocking agents (tocilizumab and siltuximab) with or without steroids are the mainstay of management for cytokine release syndrome, whereas steroids are the mainstay for the management of neurotoxicity. Another potential agent for managing these symptoms includes the interleukin 1 blocking agent anakinra.119

American Society for Transplantation and Cellular Therapy consensus grading for immune effector cell associated neurotoxicity syndrome (ICANS) in adults116

All the clinical trials on BCMA CAR T cell treatments had a high incidence of cytokine release syndrome (>80%) except for P-BCMA-101, which seemed to have a substantially lower incidence (10%). Despite this, severe cytokine release syndrome (that is, grade 3) is seen in less than 10% of patients. Neurotoxicity was reported in less than 20% of patients with severe neurotoxicity (grade 3) in less than 7% of patients. Another common side effect is cytopenia, which has also been thought to be secondary to the lymphodepleting chemotherapy, ongoing CAR T cell activity, and disruption of hematopoiesis showing severe hypocellularity in the bone marrow, but most patients recover with time.120121

Early recognition of cytokine release syndrome and ICANS and prompt intervention after CAR T cell treatment is vital to prevent serious consequences, although the optimal timing for intervention and benefit of prophylactic treatment is yet unknown.122 The CAR T cell therapy associated toxicity (CARTOX) working group has developed a management approach for these syndromes, based on multidisciplinary grades.123 In cytokine release syndrome, patients with grade 1 are usually managed with supportive care, those with grade 2 are managed with the anti-interleukin 6 receptor tocilizumab with or without steroids in addition to supportive care, and those with grade 3-4 are managed in the intensive care unit with aggressive supportive care, vasopressors, oxygen, tocilizumab, and steroids. Patients with grade 1 and 2 ICANS are managed supportively but an electroencephalogram is done to rule out electrical seizures and imaging of the brain to rule out edema. Patients with grade 3 and 4 ICANS need steroids and more aggressive supportive care.120

Bispecific monoclonal antibodies direct a hosts immune system (more specifically cytotoxic T cells) against cancer cells by binding CD3 on T cells with a target protein on cancer cells (fig 6).124 A type of bispecific antibody is the bispecific T cell engager (BiTE), which differs from other bispecific antibodies by containing two different single chain variable fragments connected by a linker. BiTEs often have a short half life, requiring continuous infusion to maintain efficacy.125 The first BiTE to receive FDA approval for treatment in relapsed and refractory acute lymphoblastic leukemia is Blinatumomab, a bispecific antibody that engages T cells to CD19 positive cells.126 Because BiTEs engage and activate the patients own immune cells, they have a toxicity profile similar to CAR T cells including cytokine release syndrome and ICANS.116

Structure of a bispecific antibody. BiTEs=bispecific T cell engagers

AMG 420 (previously named BI 836909) is a novel BiTE targeting BCMA on myeloma cells and CD3 on T cells, which has induced multiple myeloma cell lysis in preclinical models.127 In the first-in-human phase I study of AMG 420 in patients with at least two lines of treatment, AMG 420 was given as a continuous infusion with a pump for four week infusions, six week cycles, and a maximum of 10 cycles. The maximum tolerated dose was 400 g/day; seven (70%) of 10 patients responded to this dose. Serious adverse events were seen in 48% of patients, which were most commonly infections; and two patients had reversible grade 3 polyneuropathies. Cytokine release syndrome developed in 38% of patients, with no toxicity in the central nervous system.109 A phase Ib trial with AMG 420 is currently ongoing and although this drug looks promising, the continuous intravenous infusions present logistical challenges for patients and healthcare systems (table 2). AMG 701 is a modified version of AMG 420 (by addition of an Fc domain) with an extended half life that is suitable for dosing once a week and is being investigated in a phase I study.128

Another BCMA bispecific antibody, CC-93269, is being studied in an ongoing phase I clinical trial. This humanized 2+1, immunoglobulin G 1 based, T cell engager binds to BCMA bivalently on myeloma cells and CD3 monovalently on T cells. The bivalent binding could lead to improved potency, tumor targeting, and retention.129 All doses (range 0.15-10 mg) were given intravenously over two hours weekly for the first three cycles, every two weeks for the next three cycles, and then monthly. The most common treatment emergent adverse events of grade 3 or higher included neutropenia, anemia, and infections. Cytokine release syndrome was seen in 77% of patients, with all events developing after the first dose and less common with subsequent doses. The incidence increased with higher doses, and only one patient had cytokine release syndrome of grade 3 or higher leading to their death. In 30 patients treated, the overall response rate was 43.3% and dose dependent. The overall response rate was 88.9% in nine patients in the highest dose cohort.110

Teclistamab (JNJ-64007957) is a humanized, immunoglobulin G-4 based, bispecific DuoBody antibody that binds to BCMA and CD3 that is being studied in a phase I clinical trial. In the dose escalation part, 78 patients received doses ranging from 0.3 g/kg to 720 g/kg. The drug is given intravenously every week, with one to three step-up doses given within one week before the full dose. The overall response rate was dose dependent with no responses at doses 0.3-19.2 g/kg, 30% at 38.4-180 g/kg, and 67% at 270 g/kg. Cytokine release syndrome was seen in 56% of patients overall and 65% patients at doses over 38.4 g/kg. The most common adverse events at grade 3 or higher that were related to treatment were cytopenias and infections (table 2).111

Antibody drug conjugates are complex molecules composed of an antibody that targets cancer cells and are linked to a biologically active cytotoxic drug (known as the payload; fig 7).125 Belantamab mafodotin (GSK2857916) is a novel humanized and afucosylated (to improve antibody dependent cell mediated cytotoxicity) antibody drug conjugate that targets BCMA. It consists of an anti-BCMA monoclonal antibody conjugated to monomethyl auristatin F, a potent microtubule inhibitor.130 This antibody drug conjugate was shown to have selective myeloma cell killing in vitro and in vivo thus setting the stage for clinical trials.130131

Structure of an antibody drug conjugate

This antibody was studied in a two part phase I study. The drug was well tolerated with no dose limiting toxicities, although corneal events (such as blurry vision, dry eyes, photophobia) were seen in about 58% of patients; these events are a known toxicity of monomethyl auristatin F.132 In the dose expansion phase, 35 patients were treated, and the overall response rate was 60% with a median progression free survival 12 months.133 In a phase II, two arm study, the antibody was used in patients with relapsed and refractory multiple myeloma who had failed at least three lines of treatment. The overall response rate was 31% at the 2.5 mg/kg dose and 34% at the 3.3 mg/kg dose, which was significantly lower than the phase I study. The corneal changes or keratopathy were seen in 70% and 75% of patients, respectively. Owing to the similar response rates with the 2.5 mg/kg and 3.3 mg/kg doses and a more favorable side effect profile with the lower dose, 2.5 mg/kg will be the dose used for future studies.112 Based on these data, belantamab is the first anti-BCMA treatment to be FDA approved for relapsed and refractory multiple myeloma patients who have received four prior treatments including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

Preliminary results for another study with 18 patients treated on the belantamab, bortezomib, and dexamethasone arm was presented recently, with an overall response rate of 78%; however, all 18 patients developed grade 1-3 keratopathy.113 This visual toxicity is a unique but potentially serious side effect to this drug that needs close monitoring with an ophthalmologist. Another antibody drug conjugate, DFRF4539A, is an anti-FcRH5 (also known as FcRL5) antibody conjugated to monomethyl auristatin and has shown limited activity and high incidence of toxicity in a phase I study; therefore, it was unsuccessful for this disease (table 2).134135

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Emerging immunotherapies in multiple myeloma - The BMJ

ADC Therapeutics Submits Biologics License Application to the U.S. Food and Drug Administration for Loncastuximab Tesirine for Treatment of Relapsed…

LAUSANNE, Switzerland--(BUSINESS WIRE)--ADC Therapeutics SA (NYSE: ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, today announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for loncastuximab tesirine (Lonca) for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The completion of our first BLA submission to the FDA is a significant milestone for ADC Therapeutics and takes us one step further in our evolution toward becoming a commercial-stage organization, said Chris Martin, Chief Executive Officer of ADC Therapeutics. We are grateful to the trial participants and investigators and to all our employees for their commitment to this clinical program, and we look forward to working with the FDA to bring Lonca to patients as quickly as possible.

The BLA submission is based on data from LOTIS 2, the pivotal Phase 2 multi-center, open-label, single-arm clinical trial evaluating the efficacy and safety of Lonca in patients with relapsed or refractory DLBCL following 2 lines of prior systemic therapy. In June 2020, the company presented maturing data from LOTIS 2 at the virtual 25th Congress of the European Hematology Association. As of the April 6, 2020 data cut-off date, 145 patients were enrolled in the trial and patients had received a median of 3 prior lines of therapy. Lonca demonstrated an overall response rate of 48.3% (70/145 patients) and a complete response rate of 24.1% (35/145 patients). The tolerability profile was generally manageable, with the most common grade 3 treatment-emergent adverse events in 10% of patients being: neutropenia (25.5%) with low incidence of febrile neutropenia (3.4%), thrombocytopenia (17.9%), GGT increased (16.6%) and anaemia (10.3%).

A critical unmet need remains for heavily pretreated patients with relapsed or refractory DLBCL, including those with a poor prognosis, those who never responded to prior therapy and those who received prior stem cell transplant, said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. Based on the anti-tumor activity, durability and generally manageable tolerability Lonca has demonstrated in LOTIS 2, we believe Lonca has the potential to fill this need.

The company has also initiated LOTIS 5, a Phase 3 confirmatory clinical trial of Lonca in combination with rituximab, which is intended to support a supplemental BLA for Lonca to be used as a second-line therapy for the treatment of relapsed or refractory DLBCL.

About Loncastuximab Tesirine (Lonca)

Loncastuximab tesirine (Lonca, formerly ADCT-402) is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody directed against human CD19 and conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin. Once bound to a CD19-expressing cell, Lonca is designed to be internalized by the cell, following which the warhead is released. The warhead is designed to bind irreversibly to DNA to create highly potent interstrand cross-links that block DNA strand separation, thus disrupting essential DNA metabolic processes such as replication and ultimately resulting in cell death. CD19 is a clinically validated target for the treatment of B-cell malignancies.

Lonca is being evaluated in LOTIS 2, a pivotal Phase 2 clinical trial in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), LOTIS 3, a Phase 1/2 trial in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL), and LOTIS 5, a Phase 3 confirmatory clinical trial in combination with rituximab in patients with relapsed or refractory DLBCL.

About ADC Therapeutics

ADC Therapeutics SA (NYSE:ADCT) is a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors. The Company develops ADCs by applying its decades of experience in this field and using next-generation pyrrolobenzodiazepine (PBD) technology to which ADC Therapeutics has proprietary rights for its targets. Strategic target selection for PBD-based ADCs and substantial investment in early clinical development have enabled ADC Therapeutics to build a deep clinical and research pipeline of therapies for the treatment of hematological and solid tumor cancers. The Company has multiple PBD-based ADCs in ongoing clinical trials, ranging from first in human to pivotal Phase 2 clinical trials, in the USA and Europe, and numerous preclinical ADCs in development.

Loncastuximab tesirine (Lonca, formerly ADCT-402), the Companys lead product candidate, has been evaluated in a 145-patient pivotal Phase 2 clinical trial for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) that showed a 48.3% overall response rate (ORR), which exceeded the target primary endpoint. Camidanlumab tesirine (Cami, formerly ADCT-301), the Companys second lead product candidate, is being evaluated in a 100-patient pivotal Phase 2 clinical trial for the treatment of relapsed or refractory Hodgkin lymphoma (HL) after having shown an 86.5% ORR in HL patients in a Phase 1 clinical trial. The Company is also evaluating Cami as a novel immuno-oncology approach for the treatment of various advanced solid tumors.

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

Forward-Looking Statements

This press release contains statements that constitute forward-looking statements. All statements other than statements of historical facts contained in this press release, including statements regarding our future results of operations and financial position, business strategy, product candidates, research pipeline, ongoing and planned preclinical studies and clinical trials, regulatory submissions and approvals, research and development costs, timing and likelihood of success, as well as plans and objectives of management for future operations are forward-looking statements. Forward-looking statements are based on our managements beliefs and assumptions and on information currently available to our management. Such statements are subject to risks and uncertainties, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors, including those described in our filings with the U.S. Securities and Exchange Commission. No assurance can be given that such future results will be achieved. Such forward-looking statements contained in this document speak only as of the date of this press release. We expressly disclaim any obligation or undertaking to update these forward-looking statements contained in this press release to reflect any change in our expectations or any change in events, conditions, or circumstances on which such statements are based unless required to do so by applicable law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.

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ADC Therapeutics Submits Biologics License Application to the U.S. Food and Drug Administration for Loncastuximab Tesirine for Treatment of Relapsed...

Oakland 24-year-old seeking multiethnic bone marrow donor – The Jewish News of Northern California

Its already hard enough for blood cancer patients to find a match through the international bone marrow registry, which pairs patients with potential donors who have the right type of tissue. But if youre Black and Jewish?

For people with multiple ethnic backgrounds who need marrow or stem cell transplants, matching is even harder.

I remember the doctor saying something like if he was an Irish white boy from Ireland, he might have a better chance, Monika Clark said about her son, 24-year-old Jordan Jackson-Clark of Oakland.

Jackson-Clark, whom his mom describes as mixed ethnicity and biracial, is likely to need a bone marrow transplant after a diagnosis of leukemia two weeks ago.

It was so out of the blue, Clark said. It was so unexpected.

Jackson-Clark had experienced a few bouts of intense stomach pain over the past summer, one strong enough to send him to the ER. Clark was concerned, but she was never expecting the recent call that they got from the doctor.

Through tears, Clark described the blow of hearing the diagnosis for her son, a Berkeley High School grad who was a camp counselor at the East Bay JCC and a member of the Jewish fraternity AEPi.

Hes just a gentle, loving young man, she said.

Jackson-Clark has acute myeloid leukemia, a cancer of the blood and bone marrow. Hes in the hospital getting chemotherapy for the next few weeks. In the meantime, knowing how difficult it will be to find a match for her son, Clark is desperately trying to get the word out about the bone marrow registry.

Please step out and do something very simple to save a life, she said.

The ethnic background of a cancer patient who needs a transplant matters, because the markers used to match a donor and patient are inherited. Having the same markers as a donor makes it a lot more likely that the patients body will accept the life-saving bone marrow or stem cells.

But the makeup of the database of potential donors is mostly white. For people of color and mixed race, the percentage of matches is 23 percent, and for white Caucasians its 77 percent, Clark said.

According to the nonprofit Gift of Life, while more than 12 percent of the American population is Black, only 4 percent on the registry are, and the percentages are similarly out of proportion for other ethnic groups.

Gift of Life was founded by Jay Feinberg, who was diagnosed with leukemia more than 20 years ago and needed a bone marrow transplant from a white Ashkenazi Jew. He sought a donor match, but at that time the database was sorely lacking in diversity. Efforts since then by his organization and others have greatly increased ethnic representation in the registry, but matches for mixed-ethnicity patients remain scarce. Jackson-Clark has the best chance of being matched with another person who is Black, white and Ashkenazi, but there simply arent many in the database.

The solution is getting more potential donors into the system. Clark is asking people to get tested with a simple cheek swab through Be the Match or any other registration service not only if they think they might be a match for her son, but also for all of the other patients out there who need matches. Optimal donor ages are 18 to 44; registration is free and can be done through the mail. That puts them on the international registry of potential donors, and the more people who are on the list, the more likely it is that they could be a match for a cancer patient.

Thats why Rabbi Yigal Rosenberg of Chabad of Santa Clara held a registration drive in February and encouraged young people to get on the list. When he got a call from Gift of Life a few days later, he thought it had something to do with the event.

They said, actually, you are a match! he said.

Rosenberg had the right kind of stem cells to help a 40-year-old man based on a swab hed given 10 years previously in New Jersey. (Whether marrow or stem cells are donated depends on the patients treatment needs.)

Im like, what are the chances? Rosenberg said. Literally I just hosted an event two days ago!

He immediately said yes and began a required series of injections to boost stem-cell production checking with another rabbi to make sure it was OK to have the shots on Shabbat as well.

This is the one thing youre allowed to compromise on, in Shabbat observance, is to save a life, he said.

Then, at the beginning of September, he drove down to San Bernardino, where he was put up in a hotel. He spent one day at the donation center attached to a machine that pumped blood out, filtered out and collected the stem cells, and returned the blood to his body. Rosenberg said the experience wasnt difficult at all.

I just felt so empowered during the entire process, he said.

He even livestreamed it on Facebook as a way to encourage more registrations, and to dispel some of the fear around donation. (Whether a patient requires the donors marrow or stem cells depends on the particular treatment protocol.)

I went right back to the hotel, jumped in the Jacuzzi for a bit and took a nap, he said. The next day he was back on his way to Santa Clara to resume his duties.

Clark, a former JCC preschool teacher, said it is important for people to know that donating stem cells and even bone marrow is not as intrusive or painful as it used to be. And anyone on the registry can always decide later that theyre not ready to donate, so getting the swab does not commit them to doing so.

The greatest Rosh Hashanah gift from the Jewish and biracial communities would be to spread the word far and wide with your communities, and to please get on the donor list by sending away for a simple and free cheek swab, she said. You just might save my or someone elses childs life.

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Oakland 24-year-old seeking multiethnic bone marrow donor - The Jewish News of Northern California