Actinium Pharmaceuticals Successfully Completes First Dosing Cohort in the Phase 1 Study of Actimab-A and Venetoclax Combination Therapy in…

NEW YORK, Sept. 23, 2020 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (the "Company" or "Actinium") today announced that it has successfully completed the first dosing cohort in the Actimab-A and venetoclax combination, multi-center Phase 1 trial for patients with Relapsed or Refractory ("R/R") Acute Myeloid Leukemia (AML) age 18 and above. All patients from the first dosing cohort (0.50 uCi/kg of Actimab-A) completed treatment and cleared their initial safety evaluation, thus allowing the study to proceed to the second dose cohort of 1.0 uCi/kg Actimab-A added to venetoclax. In a poster presentation at the American Association of Cancer Research (AACR) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting MCL-1, a protein shown to mediate resistance to venetoclax. The ongoing Phase 1 study was planned to replicate this synergy in a clinical setting. Actinium plans to report study proof of concept results in 2021.

Venetoclax is a B-Cell Lymphoma 2 (BCL-2) inhibitor jointly developed and marketed by AbbVie and Genentech that is approved in combination with hypomethylating agents ("HMAs") for patients with AML. The use of venetoclax has become widespread in the treatment of fit and unfit patients with R/R AML following its inclusion in the recently expanded National Comprehensive Cancer Network ("NCCN") guidelines. Actinium's preclinical research has demonstrated that by adding Actimab-A to venetoclax, the targeted internalized radiation from Actimab-A can deliver potent AML cell killing, as well as effectively deplete MCL-1 levels. The overexpression of MCL-1, a member of the BCL-2 family which venetoclax does not inhibit, promotes resistance to venetoclax. Thus, Actimab-A reverses resistance to venetoclax and has independent anti-leukemic activity mediated by CD33 as well.

"We are pleased to confirm that the second combination trial in our CD33 program is advancing through the dose escalation study as planned. Despite approval in multiple blood cancers, including AML, most AML patients are not cured with venetoclax regimens and eventually relapse. Based on the preclinical data, synergy with venetoclax and Actimab-A should lead to higher remission rates in R/R AML," said Dr. Mark Berger, Actinium's Chief Medical Officer. "We continue to generate promising data from our broader combination program. For example, the Actimab-A combination trial with chemotherapy agent CLAG-M increased the complete response rate compared to CLAG-M alone in R/R AML patients by 60%. We expect to complete the proof of concept Actimab-A venetoclax combination trial in 2021."

This Phase 1 study is a multicenter, open label trial of Actimab-A added to venetoclax for patients with CD33 positive R/R AML. The study will continue to enroll patients that have been previously treated with venetoclax as well as venetoclax nave patients. Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program at the UCLA Medical Center is the Principal Investigator for this study. The trial is also active at the University of Louisville.

Sandesh Seth, Actinium's Chairman and Chief Executive Officer, said, "We continue to advance the CD33 program for fit and unfit R/R AML patients as there is still a significant unmet need despite multiple recently approved agents. These therapeutic agents are not curative and patients continue to experience low response rates and/or high relapse rates. Our CD33 program, which also includes the Actimab-A CLAG-M combination trial, is anchored in leveraging mechanistic synergies of Actimab-A with approved or novel therapeutic agents in order to improve patient outcomes. We look forward to multiple clinical trial updates by year-end from our three ongoing trials in R/R AML, including our Iomab-B SIERRA Phase 3 pivotal trial."

Rationale for Actimab-A Venetoclax Combination Trial

This Phase 1/2 trial is a multicenter, open label trial of Actimab-A (lintuzumab-Ac225) added to venetoclax for patients with CD33 positive relapsed/refractory (R/R) Acute Myeloid Leukemia. The Phase 1 portion of the study is designed to determine the maximum tolerated dose (MTD) of Actimab-A added to venetoclax for R/R AML. The Phase 2 portion of the trial will assess the percentage of patients with CR, CRh, or Overall Response (CR + CRh), up to six months after the start of the treatment without receiving other AML therapies. The trial will enroll R/R AML patients who have been treated with venetoclax as well as venetoclax-nave patients. At the 1.0 uCi/kg dose, Actimab-A is administered on Day 1 of each cycle for four cycles and venetoclax is taken on Days 1-21 of each cycle for up to 4 cycles. Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery. Gary Schiller, MD, Professor, Hematology-Oncology and Director, Hematologic Malignancy/Stem Cell Transplant Program at the UCLA Medical Center is the Principal Investigator for this study.

More information on the clinical trial design is available at clinicaltrials.gov (NCT03867682).

About Actinium's CD33 Program (Actimab-A)

Antibody Radiation Conjugate (ARC) Actimab-A targets the CD33 antigen that is expressed on virtually all AML cells with the antibody lintuzumab which delivers potent alpha radiation via its Actinium-225 radioisotope payload. Blood cancers like AML are highly sensitive to radiation but cannot treated with the current standard of external beam delivery because the disease is too widespread throughout the body. The combination of targeted radiation with Actimab-A potentially allows for greater cancer cell death than a standalone chemotherapy regimen such as CLAG-M or venetoclax, which are frequently used in the treatment of fit and unfit patients with relapsed or refractory AML per National Comprehensive Cancer Network (NCCN) guidelines. Prior clinical results in over 100 patients treated with Actimab-A, including a Phase 1/2 trial of 58 patients, demonstrated a safety profile with minimal non-hematologic toxicities and an unmatched ability to deliver attenuated doses of radiation internally to CD33 expressing cancer cells. In the Phase 1/2 trial, Actimab-A as a single agent produced a 69% remission rate (CR, CRi, CRp) at high doses in patients with newly diagnosed AML but Actinium elected to pursue low dose combination trials for therapeutic development based on observed myelosuppression. In the Actimab-A CLAG-M Phase 1 combination trial, the second cohort with CLAG-M plus the 0.50 uCi/kg dose showed that 86% (6/7) of patients achieved complete remission (CR/CRi) after receiving the 0.50 uCi/kg dose of Actimab-A. This is a nearly 60% increase over the remission rate reported in a trial of seventy-four patients with relapsed or refractory AML who received CLAG-M alone. The company expects trial results, including the third dose cohort, in 2020. The Actimab-A Venetoclax Phase 1 trial continues to enroll patients in a maximum tolerated dose and expects to announce proof-of-concept results in 2021.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, I-131 apamistamab (Iomab-B) is being studied in the ongoing pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over fifty percent enrolled and positive single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. I-131 apamistamab will also be studied as a targeted conditioning agent in a Phase 1/2 anti-HIV stem cell gene therapy with UC Davis and is expected to be studied with a CAR-T therapy in 2020. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 alpha ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 100 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc. Website: https://www.actiniumpharma.com/

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Investors: Clayton Robertson Actinium Pharmaceuticals, Inc. crobertson@actiniumpharma.com

Hans Vitzthum LifeSci Advisors, LLC Hans@LifeSciAdvisors.com (617) 535-7743

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SOURCE Actinium Pharmaceuticals, Inc.

Company Codes: AMEX:ATNM

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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

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...

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...