On June 23, 2021 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for blood cancers and serious hematologic diseases, reported that the results of a Phase 3 clinical study of omidubicel have been published in Blood, the official journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Gamida Cell, JUN 23, 2021, View Source [SID1234584288]). Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell transplant solution for patients with hematologic malignancies.

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The results demonstrate that transplantation with omidubicel leads to faster neutrophil and platelet recovery compared to a standard umbilical cord blood graft, and results in fewer early bacterial and viral infections and less time in the hospital.

"We are pleased that the data from this well-conducted international Phase 3 trial have been published in Blood, the highly respected, peer-reviewed journal of the American Society of Hematology (ASH) (Free ASH Whitepaper)," said Ronit Simantov, M.D., chief medical officer of Gamida Cell. "The robust results of this clinical trial have demonstrated that omidubicel could provide an important new option for patients with hematologic malignancies in need of a bone marrow transplant."

Data from this study were previously presented at the Transplantation & Cellular Therapy Meetings of the American Society of Transplantation and Cellular Therapy and Center for International Blood & Marrow Transplant Research, and most recently during the Presidential Symposium at the 47th Annual Meeting of the European Society for Blood and Marrow Transplantation. The pivotal study was an international, multi-center, randomized Phase 3 trial designed to compare the safety and efficacy of omidubicel to standard umbilical cord blood transplant in patients with high-risk hematologic malignancies undergoing a bone marrow transplant.

"Previous studies have shown that engraftment with omidubicel is durable, with some patients in the Phase 1/2 study now a decade past their transplant. The Phase 3 data reinforce omidubicel’s potential to be a new standard of care for patients who are in need of stem cell transplantation but do not have access to an appropriate matched donor," said Mitchell Horwitz, M.D., lead author of the paper and a professor of medicine at the Duke Cancer Institute.

The full Blood manuscript is available here: View Source

Details of Phase 3 Efficacy and Safety Results Shared in Blood

The intent-to-treat analysis included 125 patients aged 13–65 years with a median age of 41. Forty-four percent of the patients treated on study were non-Caucasian, a population known to be underrepresented in adult bone marrow donor registries. Patient demographics and baseline characteristics were well-balanced across the two study groups. Patients with acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome or lymphoma were enrolled at more than 30 clinical centers in the United States, Europe, Asia, and Latin America.

Gamida Cell previously reported in May 2020 that the study achieved its primary endpoint, showing that omidubicel demonstrated a statistically significant reduction in time to neutrophil engraftment, a measure of how quickly the stem cells a patient receives in a transplant are established and begin to make healthy new cells and a key milestone in a patient’s recovery from a bone marrow transplant. The median time to neutrophil engraftment was 12 days for patients randomized to omidubicel compared to 22 days for the comparator group (p<0.001).

All three secondary endpoints, details of which were first reported in December 2020, demonstrated a statistically significant improvement among patients who were randomized to omidubicel compared to patients randomized to standard cord blood graft. Platelet engraftment was significantly accelerated with omidubicel, with 55 percent of patients randomized to omidubicel achieving platelet engraftment at day 42, compared to 35 percent for the comparator (p = 0.028). Hospitalization in the first 100 days after transplant was also reduced in patients randomized to omidubicel, with a median number of days alive and out of hospital for patients randomized to omidubicel of 61 days, compared to 48 days for the comparator (p=0.005). The rate of infection was significantly reduced for patients randomized to omidubicel, with the cumulative incidence of first grade 2 or grade 3 bacterial or invasive fungal infection for patients randomized to omidubicel of 37 percent, compared to 57 percent for the comparator (p=0.027). Additional data reported in the manuscript included a comparison of infection density, or the number of infections during the first year following transplantation, which showed that the risk for grade 2 and grade 3 infections was significantly lower among recipients of omidubicel compared to control (risk ratio 0.5, p<0.001).

Data from the study relating to exploratory endpoints also support the clinical benefit demonstrated by the study’s primary and secondary endpoints. There was no statistically significant difference between the two patient groups in incidence of grade 3/4 acute GvHD (14 percent for omidubicel, 21 percent for the comparator) or all grades chronic GvHD at one year (35 percent for omidubicel, 29 percent for the comparator). Non-relapse mortality was shown to be 11 percent for patients randomized to omidubicel and 24 percent for patients randomized to the comparator (p=0.09).

These clinical data results form the basis of a Biologics License Application (BLA) that Gamida Cell plans to submit to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2021.

About Omidubicel

Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplants for patients with hematologic malignancies (blood cancers), for which it has been granted Breakthrough Status by the FDA. Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia (NCT03173937). The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit www.clinicaltrials.gov.

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

On June 23, 2021 Pfizer Inc. (NYSE: PFE) reported that the first participant has been dosed in TALAPRO-3, a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial (Press release, Pfizer, JUN 23, 2021, View Source [SID1234584287]). The study will evaluate the efficacy and safety of talazoparib, an oral poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with enzalutamide, an androgen receptor inhibitor, compared with placebo plus enzalutamide in men with DNA damage response (DDR)-deficient metastatic castration-sensitive prostate cancer (mCSPC). The first patient was dosed at a site in Glendale, California.

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"The prognosis for men with advanced prostate cancer has significantly improved since the introduction of novel hormone therapies, but additional therapeutic options are needed for the approximately 25 percent of men with tumors harboring DNA damage response (DDR) gene mutations, who may have poorer outcomes," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "By combining enzalutamide, which has a proven clinical benefit in men with metastatic castration-sensitive prostate cancer, with talazoparib, our PARP inhibitor that is active in DDR-mutated cancer, we may be able to offer a new treatment option that targets the underlying genetic mechanisms associated with DDR-mutated mCSPC."

The TALAPRO-3 trial will enroll approximately 550 men with DDR-deficient mCSPC across 285 clinical trial sites in 28 countries. The primary endpoint of the study is radiographic progression-free survival (rPFS), and overall survival (OS) is a secondary endpoint. The anticipated primary completion date is late-2024.

"With the introduction of PARP inhibitors in the metastatic castration-resistant prostate cancer setting, it is important to explore how a combination approach may impact outcomes for men with metastatic castration-sensitive disease," said Neeraj Agarwal, M.D., Professor of Oncology at the University of Utah School of Medicine, Senior Director for Clinical Research Innovation at Huntsman Cancer Institute and member of the TALAPRO-3 steering committee. "It’s exciting to be at the forefront of landmark studies like TALAPRO-3, which are helping to further our understanding of how different approaches may advance care for these men."

More information about the TALAPRO-3 trial and participating sites may be found at www.clinicaltrials.gov (NCT04821622).

Talazoparib is currently approved under the brand name TALZENNA for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Selection of patients for therapy is based on an FDA-approved companion diagnostic for TALZENNA. Talazoparib is not approved for the treatment of prostate cancer. Enzalutamide is an androgen receptor inhibitor currently approved under the brand name XTANDI and is indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and mCSPC. As part of a global agreement, Pfizer and Astellas jointly commercialize XTANDI in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.

In addition to the TALAPRO-3 trial, the combination of enzalutamide plus talazoparib is being investigated in TALAPRO-2 (NCT03395197), a two-part, Phase 3, randomized, double-blind, placebo-controlled study in men with metastatic CRPC (with and without DDR defects).

About TALAPRO-3 Trial

The Phase 3, randomized, double-blind, placebo-controlled, global TALAPRO-3 trial (NCT04821622) will enroll 550 men with DDR-deficient mCSPC across approximately 285 clinical trial sites in 28 countries. In the study, participants will be randomly assigned to one of the two treatment groups and receive either talazoparib (0.50 mg once daily) in combination with enzalutamide (160 mg once daily) or placebo capsules identical to talazoparib in combination with enzalutamide. Men with moderate renal impairment at screening may be enrolled and given a lower dose of either talazoparib (0.35 mg once daily) or the placebo.

The primary endpoint of the study is radiographic progression-free survival (rPFS), which is defined as the time from the date of randomization to first objective evidence of radiographic progression or death, whichever occurs first.

About Metastatic Castration-Sensitive Prostate Cancer

Prostate cancer is considered metastatic once it has spread outside of the prostate gland to other parts of the body, such as the lymph nodes, bones, lungs, and liver.i Men are considered castration-sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels.ii The prevalence of mCSPC in the U.S. in 2020 was estimated to be just over 41,000.iii Studies have shown that DDR defects are found in 23%-27% of metastatic prostate cancers.iv,v

About talazoparib

Talazoparib is an inhibitor of PARP enzymes, which play a role in DNA response. Preclinical studies have demonstrated that talazoparib blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death. Talazoparib is being evaluated in several ongoing clinical trials in prostate cancer, as well as other novel combinations with targeted therapies in various solid tumors.

About XTANDI (enzalutamide)

XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mCSPC).

Prescribing Information for XTANDI and TALZENNA

Please see Full Prescribing Information for XTANDI (enzalutamide) at www.Xtandi.com.

Please see Full Prescribing Information for TALZENNA (talazoparib) at www.Talzenna.com.

About the Pfizer/Astellas Collaboration

In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a global agreement to jointly develop and commercialize enzalutamide. The companies jointly commercialize enzalutamide in the United States and Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing enzalutamide outside the United States.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma.

On June 23, 2021 Aleta Biotherapeutics (‘Aleta’) and Cancer Research UK reported a collaboration to advance the early phase clinical development of Aleta’s CAR-T cell engager candidate, ALETA-001 (Press release, Aleta Biotherapeutics, JUN 23, 2021, View Source [SID1234584286]).

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Aleta is a privately held immuno-oncology company focused on transforming cellular therapeutics to allow a broad spectrum of cancer indications to be targeted, and Cancer Research UK is the world’s leading cancer charity dedicated to saving lives.

Under the terms of the clinical development partnership, Cancer Research UK’s Centre for Drug Development will fund, sponsor and conduct the first-in-human Phase 1/2a clinical trial of ALETA-001, which will be led by Dr Amit Patel’s Cellular and CAR-T therapies team at The Christie NHS Foundation Trust in Manchester, UK.

ALETA-001 has been developed to benefit people with B-cell lymphoma and leukemia whose disease has progressed after receiving CD19 CAR-T cell therapy, and it is hoped that ALETA-001 will offer a new therapy for these patients who have limited treatment options.

CAR-T cell therapy works by targeting the T cell response against cancer through the engineering of T cells to recognize CD19 proteins on the surface of lymphoma and leukemia cells*. CAR-T cell therapy is showing promising results in treating people with blood cancers who are no longer responding to current lines of treatment.

However, over half of the patients treated with CD19 CAR-T cell therapy relapse, mostly due to reduction or loss of CD19 expression. Through binding CD20 present on the surface of cancer cells, ALETA-001 reactivates the CD19 CAR-T cells by effectively ‘recoating’ the cancer cell with the target CD19 proteins** and restoring the CAR-T cells ability to recognise and engage the cancer cell.

In the Cancer Research UK-sponsored Phase 1/2a trial, patients with B-cell lymphoma/leukemia who have received CD19 CAR-T cell therapy but did not achieve a complete response or who relapsed from a complete response will be enrolled. After the recommended Phase 2 dose of ALETA-001 has been determined, Aleta will initiate a multi-center, single arm, pivotal Phase 2 trial in the United States focused on diffuse large B-cell lymphoma (DLBCL) patients. This clinical trial will be designed to support potential accelerated approval of ALETA-001.

Aleta retain the rights to further develop and commercialize ALETA-001 and will receive a licence to the results of the clinical trial from Cancer Research UK in return for undisclosed success-based milestone and royalty payments.

Paul Rennert, President, Co-Founder and Chief Scientific Officer, Aleta Biotherapeutics, said: "We are deeply honored to be partnering with Cancer Research UK to rapidly advance our lead drug candidate, ALETA-001, into the clinic. There is an urgent need to develop new therapies that can help people with B-cell cancers, such as lymphoma and leukemia, whose cancer has progressed after treatment with CD19 CAR-T cell therapy. Our collaboration with Cancer Research UK is a strong endorsement of the potential of our scientific platform to address the critical issues of CAR-T cell persistence, tumour antigen loss leading to patient relapse, and tumour antigen heterogeneity. We look forward to working with Cancer Research UK’s exceptional network of experienced clinical trial investigators and researchers to conduct the trial."

Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said: "CAR-T cell therapy has been transformative in treating patients with hard-to-treat blood cancers, but many will see their cancer return and treatment options begin to run out. ALETA-001 uses a simple yet elegant method to redirect a patient’s circulating CD19 CAR-T cells against cancer cells expressing CD20, and we hope this could be a new treatment avenue for blood cancer. This is a landmark collaboration for Cancer Research UK as it’s the first-in-human trial for a new drug that reboots CAR-T cell therapy, and we look forward to progress its early clinical development with Aleta."

Notes to editor

* CAR T cell therapy consists of T cells that have been taken from a patient and are reprogrammed in the lab to recognize cancer cells so they can target and kill them more effectively. T cells are taken from a patient and are engineered in the lab to carry a specific CD19 receptor on their surface, which will allow them to target and kill the cancer cells through binding the CD19 antigen present on B cell leukemia and lymphoma cells. The CAR-T cells are then given back to the patient to mount an immune response directed at cancer cells. CAR-T therapy is thus a patient specific personalized anti-cancer treatment.

** In order to replace and increase CD19 antigen expression on the cancer cell surface, ALETA-001 binds to CD20 on the tumour cell leading to the presentation of the CD19 extracellular domain which is recognised and engaged by circulating CD19 CAR-T cells leading to cancer cell killing. CD20 is another type of receptor found expressed on cancer cells, but it appears to be more stable than CD19 and its expression is rarely lost.

On June 23, 2021 Oncoinvent AS, a clinical stage company advancing a pipeline of radiopharmaceutical products across a variety of solid cancers, reported plans to raise a private round of financing (Press release, Oncoinvent, JUN 23, 2021, View Source [SID1234584285]). The company has engaged Arctic Securities AS and DNB Markets, a part of DNB Bank ASA, as Joint Global Coordinators and Joint Bookrunners (together, the "Managers") to advise on and carry out a private placement (the "Private Placement") estimated to raise gross proceeds to the Company of approximately NOK 150 – 200 million. The net proceeds from the Private Placement are expected to ensure financing past end of 2023, including financing of two clinical phase 2A studies (in ovarian cancer and colorectal cancer).

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The price per share in the Private Placement has been set to NOK 52, implying a total pre-money market capitalisation of NOK 744 million.

The Managers have received non-binding indications of interest from existing shareholders and new investors for a substantial part of the offering size, including pre-commitments of NOK 114 million from large existing shareholders Hadean Ventures, Geveran, RADFORSK Investeringsstiftelse, Sundt, Must Invest, Canica, MP Pensjon and Watrium.

"We are extremely satisfied to be finishing off a successful year of clinical trials with Radspherin, during which we have been able to navigate the COVID-19 pandemic and execute the phase 1 trials with solid recruitment rate. This enables us to move fast into phase 2A studies after having demonstrated that Radspherin can be administered safely and effectively. The safety profile of Radspherin is very good and we have determined the clinically relevant dose for the product," said Jan A. Alfheim, Oncoinvent CEO. "We are now looking to move forward with the clinical development of Radspherin and to focus on measuring the efficacy of the product in the upcoming phase 2A clinical trials."

Alfheim continued by saying, "We are pleased that our current investors continue to believe in the company and our technology, and we welcome their strong participation in this current round of financing."

"It has been a very busy year for Oncoinvent running two clinical trials and manufacturing of radionuclides, microparticles, and finished product as well as performing quality controls for clinical supplies at the same time as working on developing pipeline candidates. This has been performed in a cost efficient and reliable way and we thank all the employees, and collaborators, as well as the staff at the clinical trial sites, for their efforts. We will hereby thank existing and new investors for their current and future financial support of Oncoinvent," says Roy H. Larsen, Chairman of the Board.

Ingrid Teigland Akay, Oncoinvent board member and Managing Partner of Hadean Ventures which together with Geveran are the largest anchor investors in the upcoming financing round, commented: "We have been impressed by the company’s ability to run two parallel clinical trials in a very difficult year where so many trials have been impacted by the pandemic. The results we have seen so far from these trials are promising in regard to the future development of Radspherin and we are very pleased to continue to support Oncoinvent on this journey."

About RAD-18-001 and RAD-18-002

The Phase 1 open-label, dose-escalation clinical trials are designed to assess the dose, safety and tolerability of Radspherin, an α-emitting radionuclide therapy, administered into the intraperitoneal cavity in subjects with peritoneal carcinomatosis from ovarian cancer and colorectal carcinoma respectively. The trials include a dose escalation phase followed by repeated injection and expansion cohort phases at the recommended clinical dose. Key objectives in the studies include determining maximum tolerated dose, abdominal biodistribution, and preliminary anti-tumor activity. Please refer to www.clinicaltrials.gov for additional clinical trial details.

About Radspherin

Radspherin is a novel alpha-emitting radioactive microsphere suspension designed for treatment of metastatic cancers in body cavities. The radium-224 based therapeutic, Radspherin has shown strong and consistent anticancer activity at doses being essentially non-toxic in preclinical studies. It is anticipated that the product can potentially be used to treat several forms of metastatic cancer.

On June 23, 2021 Kite, a Gilead Company, reported that Fosun Kite Biotechnology Co., Ltd., a joint venture between Kite and Shanghai Fosun Pharmaceutical (Group) Co., Ltd, has received approval from the China National Medical Products Administration (NMPA) for axicabtagene ciloleucel for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma (Press release, Kite Pharma, JUN 23, 2021, View Source [SID1234584284]).

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Axicabtagene ciloleucel is the first and only commercially available chimeric antigen receptor (CAR) T-cell therapy approved in China.

"In relapsed or refractory LBCL, current standard-of-care is associated with poor long-term outcomes, so we are pleased to offer this new hope of survival for patients in China who are in need of new therapeutic options," said Terence O’Sullivan, Vice President, International Region at Kite. "Thank you to the dedicated healthcare professionals, patients and caregivers who worked with the team at Fosun Kite to make this treatment option available in China."

Axicabtagene Ciloleucel, FKC876, is an autologous CD19-directed CAR T-cell therapy manufactured in China under a license to YESCARTA (Axicabtagene Ciloleucel) from Kite.

The approval is based on results of a single-arm, open label, multi-center bridging trial (FKC876-2018-001) which has evaluated the efficacy and safety of FKC876 in the treatment of Chinese patients with refractory intermediate invasive non-Hodgkin’s lymphoma (NHL)/ large B-cell lymphoma in China.

About YESCARTA (Axicabtagene Ciloleucel)

YESCARTA is the world’s first approved CAR T-cell therapy for adult patients with certain types of non-Hodgkin lymphoma (NHL). It was approved for the US market on October 18, 2017 by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. On August 27, 2018 YESCARTA was also approved by the European Medicines Agency’s (EMA) Committee for EU markets as a treatment for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.