On March 24, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that its collaborator, Memorial Sloan Kettering Cancer Center ("MSK"), has commenced patient enrollment in the Phase 1 study evaluating Iomab-ACT for targeted conditioning prior to treatment with MSK’s CD19 targeted CAR T-cell 19-28z (Press release, Actinium Pharmaceuticals, MAR 24, 2021, View Source [SID1234577093]). Iomab-ACT is a low dose version of Actinium’s Phase 3 drug candidate Iomab-B, a CD45 targeting antibody radiation conjugate ("ARC"). Actinium and MSK were jointly awarded National Institutes of Health Small Business Technology Transfer grant funding for this first ever trial to evaluate ARC-based targeted conditioning prior to CAR-T therapy. The scientific rationale for this trial builds on preclinical data published in 2020 and is further supported by clinical observations from the SIERRA trial to justify combining MSK’s 19-28z CAR T-cell therapy with Iomab-ACT. Manufacturing of patient CAR T-cells has commenced and patient conditioning with Iomab-ACT followed by 19-28z CAR T-cell infusion is expected early in the second quarter of 2021, with proof-of-concept data expected in the second half of 2021.

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Results of a Phase 2 trial in 53 patients with relapsed and refractory B-cell acute lymphoblastic leukemia with MSK’s 19-28z CAR-T published in the New England Journal of Medicine reported complete remissions in 83% (44/53) of patients, median event-free survival (EFS) of 6.1 months and median overall survival (OS) was 12.9 months at a median follow up period of 29 months (range 1 – 65 months). There was a 26% (14/53) rate of Grade 3 of greater cytokine release syndrome (CRS), with 1 patient death as a result, and 42% of patients experienced Grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS).

Dr. Dale Ludwig, Actinium’s Chief Scientific and Technology Officer, said "MSK’s 19-28z CAR T-cell therapy has produced high response rates in patients with relapsed or refractory B-ALL who have previously undergone several lines of standard therapy. However, toxicities such as cytokine release syndrome and neurologic toxicity, as well as durability of response, remain a significant challenge. The ARC technology Iomab-ACT employs enables the delivery of targeted radiation that selective and specifically targets immune cells including those implicated in the CAR-T-associated toxicities of neurotoxicity and cytokine release syndrome. We are eager to begin treating patients in this first of its kind pilot study to explore the potential of Iomab-ACT targeted lymphodepletion to modulate the immune system and improve the safety profile of CAR T-cell therapy. We are hopeful this technology may ultimately enhance our ability to deliver CAR T-cell therapies more safely. Positive results from pilot study could have a meaningful impact on the way we condition patients for CAR-T and other adoptive cell therapies, which have transformed the treatment of patients with blood cancers."

Sandesh Seth, Actinium’s Chairman and CEO, said "This is a major milestone for Actinium and one we are very excited by. Adoptive cell therapies like CAR-T and gene therapies have emerged as some of the most promising areas in medicine and hold tremendous promise for patients, many of whom have limited or no treatment options remaining. This promise has led to a large and growing field of therapies where we intend to establish Iomab-ACT as the universal solution for targeted, non-chemotherapy conditioning, that harnesses the power of radiation. With Iomab-B nearing complete enrollment in the Phase 3 SIERRA trial for bone marrow transplant conditioning, starting to treat patients in this Iomab-ACT trial for CAR-T conditioning could not come at a better time. We look forward to continuing to build out our strategic business unit in targeted conditioning to best serve patients seeking potentially curative bone marrow transplant, adoptive cell therapy and gene therapy to improve patient access and outcomes."

About Iomab-ACT

Iomab-ACT targets cells that express CD45, an antigen found on immune cells such as lymphocytes and macrophages as well as leukemia and lymphoma cancer cells and delivers the radioisotope warhead iodine-131 to achieve cell depletion. Iomab-ACT is intended to deplete CD45+ immune cells such as macrophages that are implicated in CAR-T related toxicities and may also have an anti-tumor effect on chemo-refractory cancers. Iomab-ACT is a low dose extension of Actinium’s lead program, Iomab-B, which is being studied in a pivotal Phase 3 trial for targeted conditioning prior to a bone marrow transplant. Preclinical data supporting Iomab-ACT’s application in targeted lymphodepletion prior to ACT such as CAR-T was recently published in the journal Oncotarget (https://www.oncotarget.com/archive/v11/i39/).

In addition, clinical data with trace doses of Iomab-B has shown transient, reversible lymphodepletion in patients and drug clearance pharmacokinetics that fit within the vein-to-vein time of CAR-T manufacturing and administration.

On March 24, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported financial results and recent corporate highlights for the full year ended December 31, 2020 (Press release, Mustang Bio, MAR 24, 2021, View Source [SID1234577076]).

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Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "We are excited by the progress across our cell and gene therapy programs in 2020. Notably, MB-106 (CD20-targeted, autologous CAR T cell therapy) data were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting which showed a favorable safety profile and clinical activity, with an 89% overall response rate and 44% complete response rate in patients with relapsed or refractory B-cell non-Hodgkin lymphomas who were treated with the modified cell manufacturing process. In August, we initiated an open-label, multicenter Phase 1/2 clinical trial to evaluate the safety and efficacy of MB-102 (CD123-targeted CAR T cell therapy) in patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm ("BPDCN"). In October, initial Phase 1 data on MB-105, a PSCA-targeted CAR T cell therapy administered systemically to patients with PSCA-positive metastatic castration-resistant prostate cancer ("mCRPC"), demonstrated a 94% reduction in prostate-specific antigen, near complete reduction of measurable soft tissue metastasis by computerized tomography, and improvement in bone metastases by magnetic resonance imaging in a 73-year-old male patient with PSCA-positive mCRPC who failed eight prior therapies."

Dr. Litchman continued, "In 2021, we anticipate multiple potential data disclosures from our collaborators’ clinical trials, and we plan to have four open Mustang Investigational New Drug ("IND") applications. We look forward to advancing our lentiviral gene therapy clinical program for the treatment of X-linked severe combined immunodeficiency ("XSCID"), also known as bubble boy disease. In the second quarter, we plan to begin enrollment on our pivotal multicenter Phase 2 trial of MB-107 in newly diagnosed infants with XSCID who are under the age of two and submit an IND application for a pivotal multicenter Phase 2 trial of MB-207 for the treatment of patients with XSCID who were previously treated with hematopoietic stem cell transplant ("HSCT") and for whom re-treatment is indicated. With a robust pipeline of therapies addressing highly challenging diseases, world-class R&D collaborators, a state-of-the-art cell processing facility and an experienced team, I believe we are very well positioned to continue building a fully integrated cell and gene therapy company."

Financial Results:

As of December 31, 2020, Mustang’s cash and cash equivalents and restricted cash totaled $98.8 million, compared to $62.4 million as of December 31, 2019, an increase of $36.4 million year-to-date.
Research and development expenses were $37.2 million for the year ended December 31, 2020. This compares to $30.0 million for 2019. Non-cash, stock-based compensation expenses included in research and development were $1.4 million for the year ended December 31, 2020, compared to $0.9 million for 2019.
Research and development expenses from license acquisitions totaled $10.1 million for the year ended December 31, 2020, compared to $6.3 million for 2019. Non-cash, stock-based compensation expenses included in research and development – licenses acquired were $7.6 million for the year ended December 31, 2020, compared to $4.9 million for 2019.
General and administrative expenses were $9.5 million for the year ended December 31, 2020. This compares to $9.6 million for 2019. Non-cash, stock-based compensation expenses included in general and administrative expenses were $4.0 million for the year ended December 31, 2020, compared to $3.4 million for 2019.
Net loss attributable to common stockholders was $60.0 million, or $1.14 per share, for the year ended December 31, 2020, compared to a net loss attributable to common stockholders of $46.4 million, or $1.29 per share, for 2019.
2020 and Recent Corporate Highlights:

In February 2020, Mustang announced that the first subject treated with the modified MB-106 (CD20-targeted, autologous CAR T cell therapy) manufacturing process, developed in collaboration between Mustang Bio and the Fred Hutchinson Cancer Research Center ("Fred Hutch"), achieved a complete response at the lowest starting dose in an ongoing Phase 1/2 clinical trial. The trial is evaluating the safety and efficacy of MB-106 in subjects with relapsed or refractory B-cell non-Hodgkin lymphomas and chronic lymphocytic leukemia.
In April 2020, Mustang announced that the European Medicines Agency ("EMA") granted Advanced Therapy Medicinal Product ("ATMP") classification to MB-107, a lentiviral gene therapy for the treatment of newly diagnosed infants with XSCID.
In May 2020, Mustang submitted an IND with the U.S. Food and Drug Administration ("FDA") to initiate a pivotal multicenter Phase 2 trial of MB-107 in newly diagnosed infants with XSCID who are under the age of two. The trial is expected to enroll 10 patients who, together with 15 patients enrolled in the current multicenter trial led by St. Jude Children’s Research Hospital, will be compared with 25 matched historical control patients who have undergone HSCT. The primary efficacy endpoint will be event-free survival.
Also in May 2020, City of Hope presented two posters pertaining to MB-104, an innovative CS1 CAR T cell therapy, at the virtual 23rd Annual Meeting of the American Society of Gene & Cell Therapy.
In June 2020, Mustang raised gross proceeds of approximately $37.2 million in an underwritten public offering of common stock, including the exercise of the underwriter’s option.
In August 2020, Mustang announced that the FDA granted Rare Pediatric Disease Designations to MB-107 for the treatment of XSCID in newly diagnosed infants and to MB-207 for the treatment of XSCID in patients who were previously treated with HSCT and for whom re-treatment is indicated.
In September 2020, Mustang announced that the FDA granted Orphan Drug Designations to MB-107 for the treatment of XSCID in newly diagnosed infants and to MB-207 for the treatment of XSCID in patients who were previously treated with HSCT and for whom re-treatment is indicated.
In October 2020, Mustang announced that the first patient was dosed in a Mustang-sponsored, open-label, multicenter Phase 1/2 clinical trial to evaluate the safety and efficacy of MB-102 (CD123-targeted CAR T cell therapy) in patients with relapsed or refractory BPDCN.
Also in October 2020, Mustang announced that initial Phase 1 data on MB-105, a PSCA-targeted CAR T cell therapy administered systemically to patients with PSCA-positive mCRPC, were presented by City of Hope at the virtual 27th Annual Prostate Cancer Foundation Scientific Retreat. A 73-year-old male patient with PSCA-positive mCRPC was treated with MB-105 and lymphodepletion (a standard CAR T pre-conditioning regimen) after failing eight prior therapies. On day 28 of the patient’s treatment, MB-105 demonstrated a 94% reduction in prostate-specific antigen, near complete reduction of measurable soft tissue metastasis by computerized tomography, and improvement in bone metastases by magnetic resonance imaging.
Additionally, in October 2020, Mustang in-licensed LentiBOOST technology from SIRION Biotech GmbH for the development of MB-207.
In November 2020, Mustang signed an agreement with Minaris Regenerative Medicine GmbH to enable technology transfer and GMP clinical manufacturing of the MB-107 lentiviral gene therapy program for the treatment of XSCID in Europe.
Also in November 2020, Mustang announced that the European Commission issued a positive opinion on its application for Orphan Drug Designation for MB-107.
In December 2020, Mustang announced positive interim Phase 1/2 data on MB-106 for patients with relapsed or refractory B-cell non-Hodgkin lymphomas, which were presented at the 62nd ASH (Free ASH Whitepaper) Annual Meeting. The data demonstrated an extremely favorable safety profile and clinical activity with an 89% overall response rate and 44% complete response rate over 4 dose levels in 9 patients treated with the modified cell manufacturing process.
Also in December 2020, Mustang announced that a Phase 1 single-center, two-arm clinical trial was initiated to establish the safety and feasibility of administering MB-101 to patients with leptomeningeal brain tumors (e.g., glioblastoma, ependymoma or medulloblastoma).
In February 2021, Mustang announced encouraging MB-107 and MB-207 clinical updates from its investigator-IND XSCID trials, as well as additional consistent safety and efficacy data. On January 28, 2021, the FDA removed a CMC hold on the MB-107 Phase 2 clinical trial IND application after reviewing a comprehensive CMC package that was submitted by Mustang in late December 2020. The company expects to enroll the first patient in this pivotal multicenter trial in the second quarter of 2021 and is targeting topline data from the trial in the second half of 2022. The company also expects to file an IND in the second quarter of 2021 for its pivotal multicenter Phase 2 clinical trial of MB-207.

On March 24, 2021 InteRNA Technologies, a clinical-stage biotech company developing microRNA (miRNA)-based therapeutics with a focus on cancer, reported that preclinical data investigating the Company’s lead candidate, INT-1B3, have been published in the peer-reviewed journals Molecular Therapy – Nucleic Acids and Oncotarget (Press release, InteRNA Technologies, MAR 24, 2021, View Source [SID1234577094]). INT-1B3 is a mimic of the tumor suppressor miRNA-193a-3p and has the potential to address multiple hallmarks of cancer at the same time. The published results include data from tumor cell lines and experimental tumor models and support the high therapeutic potential of INT-1B3 in solid tumor indications.

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"Publications of our preclinical data with INT-1B3 in two highly-ranked, peer-reviewed journals represent a major milestone for our research and development team, and recognition of the innovative scientific research conducted at InteRNA in the last few years," said Dr. Michel Janicot, Chief Development Officer of InteRNA Technologies. "Documenting the molecular mechanism of action of our miR-193a-3p mimic and consequent downstream biology in cancer cells strongly supports INT-1B3 as novel promising candidate for therapeutic intervention in oncology."

In the publication in Molecular Therapy – Nucleic Acids, results of extended RNA-sequencing and transcriptome-wide analysis after transfection of the miR-193a-3p mimic (1B3) in human tumor cell lines were presented, revealing insights into the underlying molecular pathways of 1B3’s tumor suppressor functions. Differentially expressed genes mapped by Ingenuity Pathway Analysis strongly indicated upregulation of the tumor suppressive PTEN pathway as well as downregulation of many oncogenic growth factor signaling pathways. Furthermore, the analysis pointed to an extensive link of 1B3 with cancer, based on predicted negative effects on tumor cell survival, proliferation and migration as well as induction of cell death in tumor cells. These data strongly suggest that 1B3 is a potent tumor suppressor agent which targets various key hallmark pathways across cancer types.

In the publication in Oncotarget, preclinical data from different tumor cell-based assays demonstrated multi-modal effects of 1B3 on cancer cells. 1B3 was shown to efficiently reduce target gene expression in tumor cells, leading to diminished cell proliferation and survival, induction of cell cycle arrest and apoptosis, increased cell senescence, DNA damage and inhibition of cell migration. In addition, the novel lipid nanoparticle (LNP)-based formulation of 1B3, INT-1B3, demonstrated pronounced anti-tumor activity as a single agent upon systemic administration in tumor-bearing mice at well-tolerated doses.

These preclinical results contributed to the decision by InteRNA to initiate a first-in-human clinical study with INT-1B3 in patients with advanced solid tumors. The first patient in the study was dosed in February 2021. The trial is conducted in clinical study centers in the Netherlands and Belgium and topline results from the dose escalation part of the study are expected by the end of 2021.

About INT-1B3

INT-1B3’s unique mechanism of action addresses multiple hallmarks of cancer simultaneously. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components across the PTEN tumor suppressor pathway and the oncogenic PI3K/Akt and Ras/MAPK pathways resulting in inhibition of proliferation and migration and induction of cell cycle arrest and apoptosis. The triggering of the immunogenic tumor cell death (ICD) process as well as downregulation of the adenosine-A2A receptor pathway through inhibition of CD39/CD73 leads to a decrease in immunosuppressive FoxP3/Lag3 regulatory T cells and monocytic myeloid-derived suppressor cells (mMDSCs), and maturation of dendritic cells. As a result, the immune system is activated, and long-term immunity is triggered by recruitment of CD8+ effector T cells leading to decreased metastasis development and improved animal survival compared to anti-PD1 treatment.

On March 23, 2021 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported that a poster highlighting the pivotal Phase 2 ENVASARC clinical trial will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual meeting, being held April 10-15, 2021 (Press release, Tracon Pharmaceuticals, MAR 23, 2021, View Source [SID1234577038]). The poster will include an oral review by Sandra D’Angelo, M.D., from Memorial Sloan Kettering Cancer Center.

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Poster Title: ENVASARC: A Pivotal Trial of Envafolimab, and Envafolimab in Combination with Ipilimumab, in Patients with Advanced or Metastatic Undifferentiated Pleomorphic Sarcoma or Myxofibrosarcoma who have Progressed on Prior Chemotherapy
Abstract Link: View Source!/9325/presentation/4849
Session Category: Phase II Clinical Trials in Progress
Date Available: April 10, 2021
Poster Number: CT239
The poster will be available on the publications page of the company’s website following presentation.

On March 23, 2021 Nuvalent, Inc., a biotechnology company creating precisely targeted therapies for clinically proven kinase targets in cancer, reported the appointment of Christopher Turner, M.D., as Chief Medical Officer (Press release, Nuvalent, MAR 23, 2021, https://www.nuvalent.com/nuvalent-appoints-christopher-turner-m-d-as-chief-medical-officer/ [SID1234580618]). Dr. Turner brings more than 20 years of clinical experience in both early- and late-stage oncology drug development, having served in physician-scientist roles in both academia and the biotechnology industry. Dr. Turner will oversee the clinical development of Nuvalent’s portfolio of innovative small molecule kinase inhibitors, including parallel lead programs in ROS1-positive and ALK-positive non-small cell lung cancer (NSCLC), which are designed to overcome the limitations of existing therapies for these clinically proven targets.

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"Chris is a dedicated physician and drug developer who has guided the early development, global registration studies, and marketing approval of multiple kinase inhibitor therapies for patients with cancer," said James Porter, Ph.D., Chief Executive Officer of Nuvalent. "I am delighted to welcome him to the Nuvalent team, where his clinical vision and proven leadership will help drive the progression of our robust pipeline through multiple near-term clinical milestones."

Dr. Turner’s career reflects an established record of leadership across a broad range of precision oncology targets and therapeutic approaches, with a focus on highly selective kinase inhibitors.

Most recently, Dr. Turner was Vice President of Clinical Development at Blueprint Medicines, where he oversaw the development and approval of kinase inhibitor GAVRETO (pralsetinib) in RET fusion positive NSCLC and RET altered thyroid cancer. Additionally, Dr. Turner oversaw development programs for kinase inhibitors targeting FGFR4 and EGFR with emergent resistance mutations.

Dr. Turner previously led the development of novel antibody-drug conjugate (ADC) and immune-oncology pipeline compounds at Celldex Therapeutics, and prior to that, the clinical development at Ariad Pharmaceuticals of two kinase inhibitors that have since been approved, ICLUSIG (ponatinib) for patients with chronic myeloid leukemia, and ALUNBRIG (brigatinib) for patients with ALK-positive NSCLC.

"Smart target selection and selective inhibitor design are critical cornerstones of successful drug development, and the clear foundation for Nuvalent’s focused discovery efforts," said Dr. Turner. "I look forward to working together with this highly dedicated team to deliver tangible benefits to patients with cancer through innovative new kinase inhibitors that address treatment resistance, minimize adverse events, and drive more durable responses."

Dr. Turner is board certified in both Pediatrics and Pediatric Hematology and Oncology. He received his M.D. from the University of Rochester School of Medicine and Dentistry and completed a residency in General Pediatrics at the Children’s National Medical Center in Washington, D.C, as well as fellowships in both Pediatric Hematology/Oncology and Pediatric Neuro-Oncology at Duke University Medical Center. Dr. Turner has held positions as Director of the Pediatric Neuro-Oncology Outcomes Clinic at the Dana-Farber Cancer Institute/Children’s Hospital Boston and as an Instructor of Pediatrics at Harvard Medical School, where he treated children and young adults with brain tumors.

Nuvalent launched in January 2021 with a $50M Series A financing from Deerfield Management. The company’s novel molecules have been designed through Nuvalent’s proprietary discovery efforts to specifically solve for the dual challenges of kinase resistance and selectivity.