Genprex Provides Update on Development of its Oncoprex Immunogene Therapy in Combination with Immunotherapy for Non-Small Cell Lung Cancer

Source:  Genprex, Inc. July, 1, 2019

Genprex, Inc. (NASDAQ: GNPX), a clinical stage gene therapy company, today provided an update on development of its lead drug candidate, Oncoprex™ immunogene therapy, in combination with immunotherapy for the treatment of non-small cell lung cancer (NSCLC).

In July 2018, the company entered a Sponsored Research Agreement with The University of Texas MD Anderson Cancer Center (“MD Anderson”) to fund a research study entitled, “A Novel Therapeutic Approach for the Treatment of Cancer Using a Combination of the Multifactorial Tumor Suppressor Gene TUSC2 and Immunotherapy.” The TUSC2 gene is the active agent in Genprex’s Oncoprex immunogene therapy. The study was budgeted to cost $2.03 million.

The study aimed to develop a novel therapeutic approach for the treatment of cancer using a combination of the tumor suppressor gene TUSC2 and immunotherapy, including immune checkpoint inhibitors and anti-PD1 and/or anti-CTLA-4 antibodies. A specific objective of the study was to validate therapeutic efficacy of the TUSC2 and immune checkpoint blockade combination in humanized cancer mouse models. This milestone was completed with positive results presented in a poster by Genprex’s collaborators from MD Anderson at the American Association of Cancer
Research Meeting in April 2019, which is available on the company’s website.

Research under the Sponsored Research Agreement is continuing. Further aims of the research include evaluating TUSC2 in combination with immunostimulatory adjuvants and targeted small molecule drugs. Additional goals of the study also include identification of biomarkers that predict response to TUSC2-immunotherapy combinations

Based on data from this study and data from prior clinical and pre-clinical studies, Genprex is working with its Scientific Advisory Board and outside consultants to design a clinical trial for the study of Oncoprex in combination with a checkpoint inhibitor for treatment of non-small cell lung cancer, with the goal of being in a position to enroll patients in the first quarter of 2020.
“Recent studies have shown that less than half of cancer patients qualify for approved immunotherapies based on the patient’s PD-1 or PD-L1 protein expression level,” said Julien Pham, President and Chief Operating Officer of Genprex. “Current immunotherapy treatment is only benefitting a small number of cancer patients. We are working to fill this gap by combining our lead drug candidate with approved immunotherapies to give patients more treatment options. The preclinical studies have shown encouraging data that this combination could be a viable treatment option for late-stage non-small cell lung cancer.”

About Genprex, Inc.
Genprex, Inc. is a clinical stage gene therapy company developing potentially life-changing technologies for cancer patients, based upon a unique proprietary technology platform, including Genprex’s initial product candidate, Oncoprex™ immunogene therapy for non-small cell lung cancer (NSCLC). Genprex’s platform technologies are designed to administer cancer fighting genes by encapsulating them into nanoscale hollow spheres called nanovesicles, which are then administered intravenously and taken up by tumor cells where they express proteins that are missing or found in low quantities. Oncoprex has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for apoptosis, or programmed cell death, in cancer cells, and modulates the immune response against cancer cells. Oncoprex has also been shown to block mechanisms that create drug resistance. Visit the company’s web site at www.genprex.com or follow Genprex on Twitter, Facebook and LinkedIn.

Genprex Retains Addison Whitney for Drug Nomenclature Branding

Source:  Genprex, Inc. May 8, 2019

Genprex takes next steps toward identifying drug name for future commercialization

Genprex, Inc. (NASDAQ: GNPX), a clinical-stage gene therapy company, today announced that it has taken a significant step toward commercialization of its lead drug candidate by retaining the services of leading pharmaceutical branding agency, Addison Whitney. Addison Whitney, a Syneos Health company, will draw from its 28-year history to oversee the proprietary and non-proprietary drug naming process for Genprex’s lead drug candidate, currently known as Oncoprex™ immunogene therapy, for non-small cell lung cancer. Oncoprex immunogene therapy has shown promise in targeting and treating non-small cell lung cancer (NCSLC) through its proprietary technology platform, which transports cancer-fighting genes to cancerous cells by encapsulating the genes into nanoscale hollow spheres, called nanovesicles, which are then administered intravenously.

Addison Whitney has a proven track record of helping pharmaceutical companies achieve growth through brand differentiation and creative naming practices, most recently leading well-known drugs such as Harvoni and Letairis through the regulatory naming approval process.

“At Addison Whitney, our guiding principle is to work with companies who are making great advances in medicine to bring solutions to those who need them most,” said Joe Daley, Addison Whitney’s President. “We believe Genprex is doing just that, and we couldn’t be more excited to work with them.”

“Retaining Addison Whitney is an important step in bringing our drug candidate to market,” said Genprex’s Chairman and CEO, Rodney Varner. “Obtaining regulatory approval of proprietary and non-proprietary drug names is a necessary step in securing marketing approval, and Addison Whitney has an impressive track record in obtaining such name approvals.”

Genprex is conducting a Phase I/II clinical trial of drug candidate Oncoprex in combination with erlotinib against non-small cell lung cancer at a major academic cancer center in Houston, Texas. The company is also conducting preclinical studies to evaluate Oncoprex in combination with immunotherapies at the same cancer center.

The American Cancer Society estimates that more than 140,000 people die from lung cancer in the United States each year, which is more than the number of people who die annually from colon, breast and prostate cancers combined. NSCLC is the most common form of lung cancer globally, representing 80 percent of lung cancer diagnoses worldwide, and research shows that the five-year survival rate for late stage NSCLC is less than 5%. Genprex is working to bridge a critical gap in lung cancer treatment by combining its immunogene therapies with approved targeted therapies and immunotherapies to provide treatments to large patient populations who would not otherwise be candidates for those approved drugs, or who receive those drugs for some period and then become resistant to them.

About Addison Whitney
Addison Whitney, a Syneos Health company, is a global leader in pharmaceutical and healthcare brand development, creating hundreds of strong, long-lasting brands in collaboration with established and emerging companies. For nearly 30 years we’ve helped our clients capture marketplace opportunities and establish sustained differentiation through creative naming, imaginative design, comprehensive brand strategy and insightful market research. Headquartered in Charlotte, N.C., Addison Whitney has offices in New York, Chicago, San Francisco, Seattle, London, Munich and Tokyo. For more information, visit addisonwhitney.com.

About Genprex, Inc.
Genprex, Inc. is a clinical stage gene therapy company developing potentially life-changing technologies for cancer patients, based upon a unique proprietary technology platform, including Genprex’s initial product candidate, Oncoprex™ immunogene therapy for non-small cell lung cancer (NSCLC). Genprex’s platform technologies are designed to administer cancer fighting genes by encapsulating them into nanoscale hollow spheres called nanovesicles, which are then administered intravenously and taken up by tumor cells where they express proteins that are missing or found in low quantities. Oncoprex has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for apoptosis, or programmed cell death, in cancer cells, and modulates the immune response against cancer cells. Oncoprex has also been shown to block mechanisms that create drug resistance. Visit the company’s web site at www.genprex.com or follow Genprex on Twitter at twitter.com/genprex, Facebook at facebook.com/genprexinc, and LinkedIn at linkedin.com/company/genprex.

Actinium Highlights Two Presentations at the Health Physics Society Annual Meeting Supporting the Safety Profile of Iomab-B for SIERRA Trial Caregivers

Source:  Actinium Pharmaceuticals, Inc. 7/11/19

- Studies observed minimal cumulative radiation exposure to clinical staff providing care to patients treated with Iomab-B in the SIERRA trial of 0.09 mSv, contributing minimal exposure to the 50 mSv annual occupational dose limit

Actinium Pharmaceuticals, Inc.  (NYSE AMERICAN: ATNM) ("Actinium") today highlighted its presence at the Health Physics Society ("HPS") 64^th Annual Meeting that is being held July 7^th – 11^th in Orlando, Florida. During HPS, Actinium presented the findings of two studies that support the safety of healthcare professionals who provide care to patients treated with Iomab-B, Actinium's lead product candidate, which is being studied in the pivotal Phase 3 SIERRA trial. The studies evaluated radiation exposure to healthcare professionals who cared for patients treated with Iomab-B and the exposure from handling blood samples from patients following Iomab-B infusion. Both studies reported minimal radiation exposure to the respective healthcare professionals. One study of 105 healthcare professionals from 5 SIERRA sites that provided care to patients receiving Iomab-B observed a mean cumulative radiation exposure of 0.09 mSv or millisieverts, which is significantly less than the 50 mSv annual occupational dose limit for staff. Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the CD45 targeting antibody, apamistamab, and the radioisotope iodine-131 that is intended to be a re-induction and conditioning agent prior to a BMT or Bone Marrow Transplant. The SIERRA trial is a multicenter, 150 patient study for patients with active, relapsed or refractory AML or Acute Myeloid Leukemia that is the only randomized Phase 3 trial to offer a potentially curative BMT to this patient population for which there is no standard of care.

Details of the HPS presentations on Iomab-B are as follows:

Title: Occupational Radiation Exposures to Clinical Staff Working With ¹³¹I – Iomab-B
Summary: Data from 105 healthcare professionals from five SIERRA sites was analyzed. Staff monitored when only providing care to Iomab-B treated patients had a mean cumulative exposure of 0.07 mSv despite high levels of radiation being administered with targeted Iomab-B while staff who provided care for multiple patients, including those receiving other forms or radiation therapy, had a mean cumulative exposure of 0.11 mSv. Radiation exposure levels to all staff were found to be minimal, with mean cumulative exposure of 0.09 mSv, contributing minimal exposure to the 50 mSv annual occupational limit. The study sited training, education, customized physical shielding and more advanced safety procedures as leading to minimal additional radiation exposure.

Title: Iomab-B Study Blood Sample Handling and Occupational Radiation Extremity Exposure
Summary: Radiation exposure levels were minimal and not a safety concern to clinical staff involved in blood specimen collecting and handling.

Dr. Qing Liang, Actinium's Vice President, Head of Radiation Sciences, said, "The safety of patients and site staff is our number one concern, so I am excited that the data from these studies demonstrated minimal radiation exposure to staff caring for patients in the Iomab-B SIERRA trial. I am confident that our collective efforts, together with the supportive data presented here at the Health Physics Society Meeting, will have a positive impact on the SIERRA trial, Iomab-B and our other ARC therapeutic candidates."

"Staff at clinical sites are often surprised to learn that they can be exposed to higher amounts of radiation when flying on an airplane than compared to providing care to patients treated with Iomab-B.  These study data solidly support this fact with the 0.09 mSv mean exposure to staff significantly lower than the 50 mSv annual occupational limit and even lower than the annual radiation 3 mSv, we all receive from natural background. Since joining Actinium, I have focused on building relationships with the radiation safety and nuclear medicine caregivers at existing and prospective sites for our SIERRA trial, educating site staff and working with my clinical colleagues to further optimize the SIERRA trial for patients and site staff.  I believe that such efforts bode well not only for the SIERRA trail but also for Iomab-B in a commercial setting, assuming its approval," Concluded Dr. Liang."

The Health Physics Society has nearly 4,000 members including scientists, safety professionals, physicists, engineers and other professionals from academia, industry, the federal government and national laboratories.

Dr. Mark Berger, Actinium's Chief Medical Officer, said, "The SIERRA trial is a complex study involving multiple stakeholders at sites, including transplant physicians, radiation safety officers, nuclear medicine physicians and the nursing staff who provide care that is critical for these patients. Our team has worked intensely to address the needs of each of these stakeholders and I am proud that our efforts have taken Iomab-B from the single center where it was originally studied at to 19 clinical trials sites in the SIERRA trial thus far. The two studies presented at HPS which demonstrated that staff can safely provide care to patients with minimal radiation exposure are important and augment the promising interim feasibility and safety data that we have presented from the SIERRA trial. We are focused on continuing to generate positive data from the SIERRA trial for Iomab-B as we see a tremendous opportunity to improve outcomes for a significant number of patients with our ARC's focused on targeted conditioning for BMT and cell therapies."

About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform, which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies, to target a variety of antigens that are expressed in hematological and solid tumor indications. It is developing a multi-disease, multi-target pipeline of clinical-stage ARC's targeting the antigens CD45 and CD33 for targeting 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 (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM). Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actimab-MDS is its second pivotal program for targeted conditioning that will study the ARC comprised of the anti-CD33 monoclonal antibody lintuzumab linked to the radioisotope actinium-225 in patients with high-risk MDS in combination with RIC or Reduced Intensity Conditioning prior to a BMT.  Its ACT or Adoptive Cell Therapy program targets CD45 and utilizes a lower dose of iodine-131 than Iomab-B or lutetium-177 and is intended to be used for targeted conditioning or lymphodepletion prior to CAR-T and adoptive cell therapies as a replacement to non-optimized chemotherapies, such a Flu/Cy or fludarabine and cyclophosphamide, that is used in standard practice today. Actinium also has multiple clinical trials ongoing, in startup phase, or in planning, to use its CD33 ARC in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy. It has initiated several combination trials, including a doublet combination trial with its CD33 ARC and venetoclax, a BCL-2 inhibitor, for patients with relapsed or refractory AML, a triplet combination trial with venetoclax and an HMA or hypomethylating agent and in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML. Actinium is also studying its CD33 ARC as single agent for patients with penta-refractory multiple myeloma. Its AWE technology platform enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 100 patents covering composition of matter, formulations, methods of use, the DOTA linker technology for actinium-225 applications and methods of manufacturing the actinium-225 radioisotope in a cyclotron.

Actinium Poster Detailing Actinium-225 Labeled Daratumumab Selected in Top Poster Award Competition at 2019 Society of Nuclear Medicine and Molecular Imaging Annual Meeting

Source:  Actinium Pharmaceuticals, Inc. 6/26/19

- Actinium poster selected from more than 1,110 posters presented at SNMMI awarded second place in oncology therapeutics track

- Significantly higher cell killing ability and antitumor effect observed with Ac-225 labeled daratumumab compared to unlabeled daratumumab

Actinium Pharmaceuticals, Inc.  (NYSE AMERICAN: ATNM) ("Actinium") today announced that a poster detailing Actinium's preclinical work with the CD38 antibody daratumumab, a blockbuster therapy marketed as Darzalex® by Johnson & Johnson for patients with Multiple Myeloma, labeled with the radioisotope Ac-225 or Actinium-225 has been selected as a top poster at SNMMI for inclusion in a competitive poster competition at the 2019 Society of Nuclear Medicine and Molecular Imaging Annual Meeting. The poster titled, "225AC-CD38 antibody targeting is effective and well tolerated in experimental models of lymphoma and multiple myeloma" was selected from more than 1,100 posters that were presented at this year's SNMMI and awarded second place in the Oncology: Basic, Translational & Therapy track (Click here for poster). 

Highlights from the poster include:

• Ac-225 labeled daratumumab, at an equimolar concentration, demonstrated superior antitumor activity to naked daratumumab in DAUDI lymphoma tumor xenograft model and provided a survival benefit
• Tumor cell death in cell culture was increased as much as ten-fold following exposure to Ac-225 labeled daratumumab, approaching one-hundred percent cell death in certain cell lines
• Immunoreactivity for the target antigen CD38 was similar to naked daratumumab demonstrating that arming the antibody with Ac-225 preserved daratumumab's CD38 targeting ability

Dr. Dale Ludwig, Actinium's Chief Scientific Officer, presented the poster at SNMMI.
Actinium's AWE or Antibody Warhead Enabling technology platform generated the Ac-225 daratumumab ARC or Antibody Radiation-Conjugate. Actinium's AWE platform is covered by know-how and trade secrets that cover the generation, development, methods of use and manufacturing of ARC's. Actinium's AWE intellectual property portfolio is comprised of 28 patent families and over 100 issued and pending patents having useful life extending out as far as 2039.
Dr. Ludwig commented, "We are honored that our poster was recognized for this competition from the over 1,100 posters and great work that was presented at this year's SNMMI. It was apparent from SNMMI that the radiopharmaceutical field, particularly targeted radiotherapies, is experiencing significant growth and rapid innovation. Actinium is dedicated to staying at the forefront of the field. Our commitment is evidenced by our expanded research efforts that have resulted in a significant number of new patent filings and presentations at international conferences. Further, our active research collaboration with Astellas Pharma is ongoing and we are working to complete the third and final module of the program. Through our AWE technology platform, we have demonstrated the ability to utilize multiple isotopes with multiple targeting agents to generate potent ARCs, giving us unmatched breadth and abilities in therapeutics discovery and development. Together with Actinium's clinical experience and comprehensive supply chain capabilities, we can offer partners and collaborators a turnkey solution from R&D to the clinic and beyond."

About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform, which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies, to target a variety of antigens that are expressed in hematological and solid tumor indications. It is developing a multi-disease, multi-target pipeline of clinical-stage ARC's targeting the antigens CD45 and CD33 for targeting 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 (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM). Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actimab-MDS is its second pivotal program for targeted conditioning that will study the ARC comprised of the anti-CD33 monoclonal antibody lintuzumab linked to the radioisotope actinium-225 in patients with high-risk MDS in combination with RIC or Reduced Intensity Conditioning prior to a BMT.  Its ACT or Adoptive Cell Therapy program targets CD45 and utilizes a lower dose of iodine-131 than Iomab-B or lutetium-177 and is intended to be used for targeted conditioning or lymphodepletion prior to CAR-T and adoptive cell therapies as a replacement to non-optimized chemotherapies, such a Flu/Cy or fludarabine and cyclophosphamide, that is used in standard practice today. Actinium also has multiple clinical trials ongoing, in startup phase, or in planning, to use its CD33 ARC in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy. It has initiated several combination trials, including a doublet combination trial with its CD33 ARC and venetoclax, a BCL-2 inhibitor, for patients with relapsed or refractory AML, a triplet combination trial with venetoclax and an HMA or hypomethylating agent and in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML. Actinium is also studying its CD33 ARC as single agent for patients with penta-refractory multiple myeloma. Its AWE technology platform enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 100 patents covering composition of matter, formulations, methods of use, the DOTA linker technology for actinium-225 applications and methods of manufacturing the actinium-225 radioisotope in a cyclotron.

Actinium Presents New Data Demonstrating Effective Lymphodepletion with Lutetium-177 for CAR-T at the 2019 Society of Nuclear Medicine and Molecular Imaging Annual Meeting

Source:  Actinium Pharmaceuticals, Inc.6/25/19

- Actinium's - ACT or Adoptive Cell Therapy Program now capable of using multiple warheads, including iodine-131 and lutetium-177, to achieve lymphodepletion for CAR-T and adoptive cell therapies

- CD45 targeted lymphodepletion selectively depletes lymphoid and myeloid immune cell populations while sparing platelets, red blood cells and bone marrow cells

- Actinium's patent estate for the ACT program includes the use of multiple warheads covering composition of matter and methods of use for CAR-T and adoptive cell therapies

Actinium Pharmaceuticals, Inc.  (NYSE AMERICAN: ATNM) ("Actinium") today announced at SNMMI or the 2019 Society of Nuclear Medicine and Molecular Imaging Annual Meeting that effective lymphodepletion with the radioisotope Lu-177 or lutetium-177 was achieved with its ACT or Adoptive Cell Therapy program for achieving safe, effective and transient lymphodepletion prior to the administration of CAR-T and other adoptive cell therapies. The ARC's or Antibody Radiation-Conjugates used in the ACT program combines a CD45 targeting antibody with the cell killing power of radioisotopes. 

Lymphodepletion is an important step prior to CAR-T and adoptive cell therapies that facilitates infused cells to engraft, expand and persist. Currently, chemotherapy such as Flu/Cy or Fludarabine and Cyclophosphamide are used in standard practice for lymphodepletion. Patients receiving CAR-T and other adoptive cell therapies are often heavily pre-treated and their cancer is refractory or resistant to chemotherapy. Actinium is developing its ACT program to be a potential replacement of non-specific, chemotherapy-based lymphodepletion.

In vivo animal studies demonstrated that a Lu-177 labeled CD45 ARC transiently depleted CD45 positive immune cells while sparing platelets, red blood cells and bone marrow cells. A dose response was observed with 40µCi Lu-177 having a greater lymphodepletion effect on immune cells -- including B-cells, CD8 and CD4 T-cells, NK cells, myeloid derived suppressor cells and regulatory T-cells -- than 20µCi Lu-177. In tumor bearing mice, the Lu-177 labeled CD45 ARC was given prior to adoptive cell therapy, which demonstrated enhanced tumor control when compared to mice that were untreated and those that only received adoptive cell therapy with no lymphodepletion (Click here for the SNMMI poster).

Dr. Dale Ludwig, Actinium's Chief Scientific Officer, said, "I am truly excited by these additional results from our ACT program that we have presented at SNMMI evaluating lutetium-177 for targeted lymphodepletion. The data generated exceeded my expectations and support the continued development of a Lu-177 CD45 ARC as part of our ACT program. As we work to establish collaborations and partnerships while advancing the ACT program into clinical trials, the expansion to multiple warheads will give us flexibility and utility that I trust will be well received. I look forward to highlighting our continued efforts in this area at future medical conferences and industry meetings."

The antigen CD45 is uniquely expressed on leukemia, lymphoma and immune cells making it an ideal target for targeted condition prior to BMT or Bone Marrow Transplant, CAR-T and adoptive cell therapies. Actinium's Iomab-B and ACT programs utilize the anti-CD45 antibody apamistamab. Apamistamab has been studied in over 300 patients in 13 clinical trials, including the ongoing pivotal Phase 3 SIERRA trial, across multiple hematologic indications including acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia, lymphomas and multiple myeloma. The ACT program utilizes a lower dose of the radioisotope I-131 or Iodine-131 than Iomab-B and can now also utilize Lu-177. 

Actinium presented initial feasibility data for its ACT program at the Transplantation and Cellular Therapies Meeting in February 2019. The data demonstrated that a CD45 targeting antibody labeled with  I-131 effectively depleted greater than 90% of lymphocytes in preclinical animal models (Click here for poster).

Sandesh Seth, Actinium's Chairman and CEO, said, "I am excited to add the lutetium-177 warhead to our targeted conditioning armamentarium and expand our ACT program beyond iodine-131. Our targeted conditioning ARC's are demonstrating promising results across our portfolio, including in our pivotal Phase 3 Iomab-B program for BMT and the ACT program for lymphodepletion for CAR-T and adoptive cell therapies. These therapies have the potential to significantly benefit patients and, in some instances, lead to long lasting remissions or even cures. We are confident that our targeted conditioning ARC's can increase the number of patients that can receive these important therapies and improve patient outcomes. Recognizing the growth potential of this field we are committed to continuing to drive innovation across our ARC portfolio and further strengthening our leadership position in targeted conditioning."

About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform, which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies, to target a variety of antigens that are expressed in hematological and solid tumor indications. It is developing a multi-disease, multi-target pipeline of clinical-stage ARC's targeting the antigens CD45 and CD33 for targeting 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 (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM). Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actimab-MDS is its second pivotal program for targeted conditioning that will study the ARC comprised of the anti-CD33 monoclonal antibody lintuzumab linked to the radioisotope actinium-225 in patients with high-risk MDS in combination with RIC or Reduced Intensity Conditioning prior to a BMT.  Its ACT or Adoptive Cell Therapy program targets CD45 and utilizes either a lower dose of iodine-131 than what is used with Iomab-B or lutetium-177 and is intended to be used for targeted conditioning or lymphodepletion prior to CAR-T and adoptive cell therapies as a replacement to non-optimized chemotherapies, such a Flu/Cy or fludarabine and cyclophosphamide, that is used in standard practice today. Actinium also has multiple clinical trials ongoing, in startup phase, or in planning, to use its CD33 ARC in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy. It has initiated several combination trials, including a doublet combination trial with its CD33 ARC and venetoclax, a BCL-2 inhibitor, for patients with relapsed or refractory AML, a triplet combination trial with venetoclax and an HMA or hypomethylating agent and in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML. Actinium is also studying its CD33 ARC as single agent for patients with penta-refractory multiple myeloma. Its AWE technology platform enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 110 patents covering composition of matter, formulations, methods of use, the DOTA linker technology for actinium-225 applications and methods of manufacturing the actinium-225 radioisotope in a cyclotron.

Actinium Presents New Pivotal Phase 3 SIERRA Trial Data Showing Rapid Peripheral Blast Reduction and Anti-Leukemic Effect with Single Agent Iomab-B in Older Patients with Active, Relapsed or Refractory Acute Myeloid Leukemia at 2019 ASCO Annual Meeting

Source:  Actinium Pharmaceuticals, Inc. 6/4/19

- Lower circulating leukemia tumor burden achieved prior to bone marrow transplant with single agent Iomab-B with 98% peripheral blast reduction by day 3 and 100% peripheral blast reduction by day 8

- Rapid peripheral blast clearance, as seen here after Iomab-B administration, has been demonstrated as being predictive of Complete Response and Relapse-Free Survival in patients with Acute Myeloid Leukemia after chemotherapy in multiple studies

Actinium Pharmaceuticals, Inc.  (NYSE AMERICAN: ATNM) ("Actinium") presented new data from the ongoing pivotal Phase 3 SIERRA study of Iomab-B's single agent effect in patients with active, relapsed or refractory AML or Acute Myeloid Leukemia age 55 and above. The data was presented by SIERRA investigator Benjamin Tomlinson, M.D., Adult Hematologic and Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center (Cleveland, OH) in a poster presentation at the 2019 ASCO or American Society of Clinical Oncology Annual Meeting that is being held from May 31^st – June 4^th at the McCormick Place, Chicago

Dr. Tomlinson, said, "Older patients with active, relapsed or refractory AML are an underserved patient population. These patients, particularly those with high blast counts as seen in the SIERRA trial, are not typically considered candidates for transplant, which is a potentially curative treatment for AML, and have a poor prognosis with other therapeutic options. Iomab-B has uniquely demonstrated an ability to effectively condition these patients for transplant with robust engraftment. We hypothesized that this successful engraftment is due to the myeloablation and anti-leukemic effect of Iomab-B, since these patients had a median of 30% bone marrow blasts prior to transplant. Therefore, we are highly encouraged to observe that Iomab-B as a single agent has a significant anti-leukemic effect and rapidly reduces peripheral blasts."

 The poster can be accessed on Actinium's website (Click Here).

The poster evaluated data from the first 25% of patients (38) from the SIERRA trial where a total of 29 patients received Iomab-B.  This included 19 patients who received Iomab-B directly and 10 patients who received Iomab-B via crossover after conventional care salvage chemotherapy failed to produce a complete response. Previously presented preliminary feasibility data from the SIERRA trial demonstrated that all patients receiving Iomab-B had robust BMT or Bone Marrow Transplant donor engraftment and donor chimerism without delay. The new data presented at ASCO evaluated Iomab-B's effect as a single agent on white blood cells, lymphocytes and peripheral blasts. Of the 16 patients for whom data was available, there was a median reduction of peripheral blasts of 98% by day 3 and 100% reduction by day 8 following Iomab-B administration and prior to any other pre-BMT conditioning. Rapid reduction of peripheral blasts has been observed as an independent prognostic marker that is predictive of both CR or Complete Response and RFS or Relapse-Free Survival in patients with AML after receiving cytotoxic chemotherapy. Gianfaldoni et al¹ performed an analysis of 30 newly diagnosed AML patients who were treated with cytotoxic induction chemotherapy and found that a rapid reduction of peripheral leukemia blasts correlated with responses and all patients that achieved CR had a rapid reduction of their peripheral blasts. Elliot et al², performed a retrospective analysis of 86 adult patients with AML and identified time to clearance of circulating leukemia blasts as an independent prognostic marker of RFS that superseded all other known risk factors including karyotype and number of cycles of induction therapy needed to achieve CR.

"We are delighted that Iomab-B continues to generate encouraging data in the SIERRA trial," said Dr. Mark Berger, Actinium's Chief Medical Officer. "This is the first time single agent Iomab-B clinical data has been presented and we are quite excited by the rapid peripheral blast reduction that has been observed thus far. Peripheral blast reduction is a highly relevant clinical measure and we are optimistic that it will have a positive impact on durable complete response rates, which is the primary endpoint of the SIERRA trial. We are confident that this data will be well received by SIERRA investigators and will add to the strong engraftment data that has been already reported at ASH and TCT. Collectively, we are encouraged that Iomab-B is continuing to exemplify best-in-class transplant conditioning potential for this difficult to treat patient population."

Sources:
1) Gianfaldoni et al. clearance of leukemic blasts from peripheral blood during standard induction treatment predicts the bone marrow response in acute myeloid leukemia: a pilot study. British Journal of Haematology, 2006 March 16; 134, 54-57.

2) Elliott et al. Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood. 2007 Dec 15; 110(13):4172-4. Epub 2007 Oct 1.

About Iomab-B
Iomab-B is an ARC or Antibody Radiation-Conjugate comprised of the anti-CD45 antibody apamistamab and the radioisotope iodine-131 that is intended to be a re-induction and conditioning agent prior to a BMT or bone marrow transplant. Iomab-B was developed at the Fred Hutchinson Cancer Research Center and has been studied in over 300 patients in multiple hematologic indications across 12 clinical trials in addition to the ongoing SIERRA study in older patients with active, relapsed or refractory AML or Acute Myeloid Leukemia prior to patients receiving an allogeneic BMT or bone marrow transplant. Iomab-B is Actinium's lead targeting conditioning ARC in its multi-target, multi-indication targeted conditioning pipeline that includes the Iomab-B and Actimab-MDS programs for BMT and the Iomab-ACT program that will study a lower dose of Iomab-B for lymphodepletion prior to CAR-T and other cellular therapies.

About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform, which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies, to target a variety of antigens that are expressed in hematological and solid tumor indications. It is developing a multi-disease, multi-target pipeline of clinical-stage ARC's targeting the antigens CD45 and CD33 for targeting 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 (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM). Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actimab-MDS is its second pivotal program for targeted conditioning that will study the ARC comprised of the anti-CD33 monoclonal antibody lintuzumab linked to the radioisotope actinium-225 in patients with high-risk MDS in combination with RIC or Reduced Intensity Conditioning prior to a BMT.  Its Iomab-ACT program utilizes a lower dose of Iomab-B (CD45 – I-131) that is intended to be used for targeted conditioning or lymphodepletion prior to CAR-T and adoptive cell therapies as a replacement to non-optimized chemotherapies, such a Flu/Cy or fludarabine and cyclophosphamide, that is used in standard practice today. Actinium also has multiple clinical trials ongoing, in startup phase, or in planning, to use its CD33 ARC in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy. It has initiated several combination trials, including a doublet combination trial with its CD33 ARC and venetoclax, a BCL-2 inhibitor, for patients with relapsed or refractory AML, a triplet combination trial with venetoclax and an HMA or hypomethylating agent and in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML. Actinium is also studying its CD33 ARC as single agent for patients with penta-refractory multiple myeloma. Its AWE technology platform enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 110 patents covering composition of matter, formulations, methods of use, the DOTA linker technology for actinium-225 applications and methods of manufacturing the actinium-225 radioisotope in a cyclotron.

Actinium Announces Appointment of Niva Almaula, Ph.D. as Chief Business Officer

Source:  Actinium Pharmaceuticals, Inc. 5/7/19

- Dr. Almaula was previously Head, Business Development at Advanced Accelerator Applications, Inc., a Novartis company

- Dr. Almaula to lead partnership, licensing and collaboration efforts leveraging her deep technical and domain expertise, experience and relationships in the field of targeted radiotherapy and oncology

Actinium Pharmaceuticals, Inc.  (NYSE AMERICAN: ATNM) ("Actinium") today announced the appointment of Niva Almaula, Ph.D. as Chief Business Officer, effective immediately. Dr. Almaula joins Actinium with significant experience in the targeted radiotherapy field, having most recently worked as Head, Business Development at Advanced Accelerator Applications, Inc., a nuclear medicine company acquired by Novartis for $3.9 billion in January 2018. 

As Chief Business Officer, Dr. Almaula will be focused on leading partnership, licensing and collaboration activities for Actinium's clinical-stage ARC's or Antibody Radiation Conjugates for targeted conditioning including Iomab-B, Actimab-MDS and the Iomab-ACT program, its ARC therapeutics and combinations and AWE or Antibody Warhead Enabling technology platform that is being utilized in a collaborative research partnership by Astellas Pharma, Inc.

"I am delighted to welcome Dr. Almaula to the Actinium team and look forward to working with her to execute on multiple initiatives focused on deriving maximum value from our wide array of assets," said Sandesh Seth, Actinium's Chairman and CEO. "Amidst a backdrop of growing interest for targeted radiotherapy, we have created an exciting business that encompasses our highly differentiated clinical stage ARC's, AWE technology platform, a leadership position in the utilization of actinium-225, a broad intellectual property portfolio and robust supply chain capabilities. Further, we are unique as having the only multi-target, multi-indication clinical stage pipeline in the field of targeted conditioning, which represents an exciting potential strategic business unit and enables optionality with our ARC combination and therapies, next generation ARC's and AWE platform. Considering Dr. Almaula's deep technical and domain expertise in the field of targeted radiotherapies gained during her time at Advanced Accelerator Applications, Inc. and proven business development skills, I am confident in her ability to leverage Actinium's ARC and AWE technologies to help us execute against our strategic vision."

Dr. Almaula said, "Having witnessed first hand the value creation that is possible with highly differentiated radiopharma assets, I am excited to join the Actinium team. Actinium has established an impressive leadership position in the application of radiotherapy for targeted conditioning with Iomab-B being differentiated as the only ARC and CD45 targeting agent in clinical development for targeted conditioning. By astutely leveraging its ARC approach and AWE platform, Actinium has furthered its leadership position in targeted conditioning with the Actimab-MDS trial for a patient population with significant unmet needs and the Iomab-ACT program for CAR-T and cellular therapies where recent preclinical data supports its multi-modal mechanism of action. Actinium is also a leader in the application of actinium-225 with strong IP, know-how and an established collaboration that can be further leveraged through the AWE technology platform. The blend of late-stage clinical assets and technology platform is a unique combination that affords Actinium multiple opportunities to create significant value through strategic initiatives."

Dr. Almaula comes to Actinium with twenty years of biopharmaceutical industry experience. She joins Actinium from Advanced Accelerator Applications, Inc., a Novartis company, that is focused on nuclear medicine and targeted therapies including Lutathera^® (lutetium 177 dotatate) for the treatment of neuroendocrine tumors. Advanced Accelerator Applications, Inc. was acquired by Novartis in January 2018 for $3.9 billion. Dr. Almaula joined AAAP in May 2015 where she was Head, Business Development responsible for leading the global business development activities to strategically build AAAP's oncology portfolio. During her time at AAAP, Dr. Almaula executed three exclusive licenses that expanded the company's therapeutic and diagnostic pipeline and represented AAAP to potential partners and collaborators. Prior to AAAP, she was Founder and Partner of Octane BioVentures, where she provided business development and strategy consulting services to early stage life science companies.  Previously, she worked in alliance management and business development at Dr. Reddy's Labs, Biologics and Nycomed (now Takeda). Dr. Almaula also worked for Bio-IB, LLC, a healthcare focused investment banking firm where she advised clients on licensing, M&A and business development efforts and at the Rockefeller University in its licensing department. She began her career at Mehta Partners, LLC in biotechnology equity research.

Dr. Almaula completed a post-doctoral fellowship in the Department of Neurobiology at Mount Sinai Medical Center. She earned her Ph.D. in the department of biochemistry and molecular biology from Rutgers University/University of Medicine and Dentistry of New Jersey, and her bachelor's degree in Life Sciences and Biochemistry from St. Xavier's College, Bombay University, India.

About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform, which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies, to target a variety of antigens that are expressed in hematological and solid tumor indications. It is developing a multi-disease, multi-target pipeline of clinical-stage ARC's targeting the antigens CD45 and CD33 for targeting 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 (AML), Myelodysplastic Syndrome (MDS) and Multiple Myeloma (MM). Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actimab-MDS is its second pivotal program for targeted conditioning that will study the ARC comprised of the anti-CD33 monoclonal antibody lintuzumab linked to the radioisotope actinium-225 in patients with high-risk MDS in combination with RIC or Reduced Intensity Conditioning prior to a BMT.  Its Iomab-ACT program utilizes a lower dose of Iomab-B (CD45 – I-131) that is intended to be used for targeted conditioning or lymphodepletion prior to CAR-T and adoptive cell therapies as a replacement to non-optimized chemotherapies, such a Flu/Cy or fludarabine and cyclophosphamide, that is used in standard practice today. Actinium also has multiple clinical trials ongoing, in startup phase, or in planning, to use its CD33 ARC in combination with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy. It has initiated several combination trials, including a doublet combination trial with its CD33 ARC and venetoclax, a BCL-2 inhibitor, for patients with relapsed or refractory AML, a triplet combination trial with venetoclax and an HMA or hypomethylating agent and in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone) for patients with relapsed or refractory AML. Actinium is also studying its CD33 ARC as single agent for patients with penta-refractory multiple myeloma. Its AWE technology platform enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 110 patents covering composition of matter, formulations, methods of use, the DOTA linker technology for actinium-225 applications and methods of manufacturing the actinium-225 radioisotope in a cyclotron.

Actinium Pharmaceuticals, Inc. Announces Pricing of $16.5 Million Public Offering of Common Stock and Warrants

 Source:  Actinium Pharmaceuticals, Inc. 4/18/19

Actinium Pharmaceuticals, Inc.  (NYSE AMERICAN: ATNM) ("Actinium") today announced the pricing of an underwritten public offering of 42,860,000 shares of its common stock at a combined public offering price of $0.385 per share of common stock. The Company also announced the pricing of warrants to purchase up to 42,860,000 shares of common stock at an exercise price of $0.50 per share and with a term of 5 years commencing on the date of issuance. The offering is expected to close on or about April 23, 2019, subject to the satisfaction of customary closing conditions. The gross proceeds to Actinium from this offering are expected to be $16.5 million, before deducting underwriting discounts and commissions and other estimated offering expenses payable by Actinium. Actinium intends to use the net proceeds from the sale of the common stock and warrants to fund its ongoing pivotal, Phase 3 SIERRA trial for its lead product candidate Iomab-B and progress Phase 1 trials from its refocused CD33 program to the proof of concept stage. Actinium will also use the proceeds to support its antibody warhead enabling technology platform, including its Iomab-ACT program, research and development and general working capital needs.

William Blair & Company, L.L.C. is acting as sole bookrunner for the offering.

The shares and warrants are being offered pursuant to an effective shelf registration statement (including a prospectus) on Form S-3 (File No. 333-216748) filed with the U.S. Securities Exchange Commission (the "SEC"). A preliminary prospectus supplement, dated April 17, 2019 and accompanying prospectus, dated October 24, 2017, relating to the offering have been filed with the SEC.  To obtain a copy of the preliminary prospectus supplement, dated April 17, 2019, and the final prospectus supplement (when available) for this offering, please contact William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, IL 60606, or by calling (800) 621-0687, or emailing prospectus@williamblair.com.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities, in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state or jurisdiction.

About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugates targeted conditioning technology. Actinium's lead product candidate, Iomab-B, is in a pivotal Phase 3 trial for re-induction and conditioning prior to a BMT for patients with active relapsed or refractory AML or Acute Myeloid Leukemia. BMT is the only curative treatment option for this patient population and currently no standard of care exists. Actinium's multi-disease, multi-target pipeline of clinical-stage targeted conditioning ARC's are designed to target the antigens CD45 and CD33 for patients with a broad range of hematologic malignancies including Acute Myeloid Leukemia, Myelodysplastic Syndrome and Multiple Myeloma. Actinium is also developing its proprietary AWE or Antibody Warhead Enabling technology platform which utilizes radioisotopes including iodine-131 and the highly differentiated actinium-225 coupled with antibodies to target a variety of antigens that are expressed in hematological and solid tumor cancers. The AWE technology enables Actinium's internal pipeline and with the radioisotope actinium-225 is being utilized in a collaborative research partnership with Astellas Pharma, Inc. Actinium's clinical programs and AWE technology platform are covered by a portfolio of over 110 patents covering composition of matter, formulations, methods of use and also methods of manufacturing the radioisotope Actinium-225 in a cyclotron.