Category Archives: Genetic Therapy

CAMBRIDGE, Mass.--(BUSINESS WIRE)--HighPassBio, an ElevateBio portfolio company dedicated to advancing novel targeted T cell immunotherapies, today discussed the ongoing Phase 1 trial of the companys lead product candidate, an engineered T cell receptor (TCR) T cell therapy targeting HA-1 expressing cancer cells in an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting. The Phase 1 clinical trial, which is being conducted by researchers at Fred Hutchinson Cancer Research Center, is designed to assess the feasibility, safety, and efficacy of this novel cell therapy in the treatment of leukemia following hematopoietic stem cell transplant (HSCT).

The prognosis for leukemia patients whove relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse, said Elizabeth Krakow, M.D., MSc., Assistant Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, principal investigator of the study, and presenting author. We have observed early promising indicators of anti-leukemic activity following treatment in this trial. We are eager to expand the trial to additional patients as we continue to research the feasibility, safety, and efficacy of this approach.

The abstract for the presentation titled Phase 1 Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress, can be found on the ASH website under the abstract number 137726.

To date, four patients, including one pediatric patient, have received a total of six infusions in the Phase 1 clinical trial. Patient characteristic data was shared in the oral presentation at ASH, including documented HA-1 TCR T cell persistence in blood and bone marrow up to 18 months. In some patients, clear in vivo anti-leukemic activity was observed at the first dose level, including a subject with aggressive, highly refractory T-ALL and early post-HCT relapse. No significant toxicities attributed to the T cells have been observed, including no infusion reactions or evidence of cytokine release syndrome or graft versus host disease.

The Phase 1 clinical trial is currently recruiting adult and pediatric patients who have residual disease or relapsed leukemia or related conditions following HSCT. As part of the trial, transplant patients and prospective donors may be recruited to participate in the genetic screening portion to determine eligibility. More details are available on clinicaltrials.gov under the study ID number NCT03326921.

About TCR-Engineered T Cell Therapy

A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the bodys immune system to respond to fight off and kill the tumor cells.

Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease.

Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patients native cells, and not by the cells from the stem cell transplant donor. HA-1, a known minor histocompatibility antigen, is expressed predominantly or exclusively on hematopoietic cells, including leukemic cells. There is evidence that T cells specific for HA-1 can induce a potent and selective antileukemic effect. HA-1 TCR T cell therapy is a new investigational immunotherapy for the management of post transplantation leukemia relapse.

About Leukemia post HSCT Treatment and the Risk of Relapse

Leukemia, a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, is the tenth most common type of cancer in the U.S. with an estimated 60,140 new cases and 24,400 deaths in 2016. Leukemia arises from uncontrolled proliferation of a specific type of hematopoietic (blood) cell that is critical for a functional immune system. As a result, when patients are given very high doses of chemotherapy to eradicate leukemic cells, most normal cells are killed as well, necessitating a transplant of hematopoietic stem cells from a donor to reconstitute the patients bone marrow and circulating hematopoietic cells. In some cases, the transplanted T cells from the donor can also recognize and eliminate the hematopoietic cells, including leukemia, from the recipient, thus preventing relapse. This can be described as a graft versus leukemia effect. Other hematologic disorders related to leukemia, like myelodysplastic syndrome (MDS), can also be treated in this way.

While HSCT can be curative, it is estimated that 25-50 percent of HSCT recipients relapse; leukemia relapse remains the major cause of allogeneic HSCT failure, and the prognosis for patients with post-HCT relapse is poor. Relapse occurs following allogeneic HSCT in approximately one-third of patients with acute leukemia who undergo the procedure, and most patients subsequently die of their disease.

About HighPassBio

HighPassBio, an ElevateBio portfolio company, is working to advance a novel approach to treating hematological malignancies by leveraging T cell receptor (TCR)-engineered T cells, known as TCR T cells. The companys lead program is designed to treat or potentially prevent relapse of leukemia in patients who have undergone hematopoietic stem cell transplant (HSCT). The technology was born out of research conducted at Fred Hutchinson Cancer Research Center by world renowned expert, Dr. Marie Bleakley.

About ElevateBio

ElevateBio, LLC, is a Cambridge-based creator and operator of a portfolio of innovative cell and gene therapy companies. It begins with an environment where scientific inventors can transform their visions for cell and gene therapies into reality for patients with devastating and life-threatening diseases. Working with leading academic researchers, medical centers, and corporate partners, ElevateBios team of scientists, drug developers, and company builders are creating a portfolio of therapeutics companies that are changing the face of cell and gene therapy and regenerative medicine. Core to ElevateBios vision is BaseCamp, a centralized state-of-the-art innovation and manufacturing center, providing fully integrated capabilities, including basic and translational research, process development, clinical development, cGMP manufacturing, and regulatory affairs across multiple cell and gene therapy and regenerative medicine technology platforms. ElevateBio portfolio companies, as well as select strategic partners, are supported by ElevateBio BaseCamp in the advancement of novel cell and gene therapies.

ElevateBios investors include F2 Ventures, MPM Capital, EcoR1 Capital, Redmile Group, Samsara BioCapital, The Invus Group, Surveyor Capital (A Citadel company), EDBI, and Vertex Ventures.

ElevateBio is headquartered in Cambridge, Mass, with ElevateBio BaseCamp located in Waltham, Mass. For more information, please visit http://www.elevate.bio.

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ElevateBio's HighPassBio Presents on Novel T Cell Receptor Cell Therapy for Leukemia Relapse at 62nd Annual ASH Meeting - Business Wire

NEW YORK--(BUSINESS WIRE)--Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, today announces preliminary clinical data from its Phase 1 clinical trial of RP-L301 for the treatment of Pyruvate Kinase Deficiency (PKD), showing significant improvement in hemoglobin levels and transfusion independence over the initial 3-months following therapy. These results were presented virtually at the 62nd American Society of Hematology (ASH) Annual Meeting in a poster presentation.

The positive preliminary clinical results for RP-L301 point to a potential path to transform the management of PKD using an approach that addresses the root cause of the disease for the first time at the genetic level, said Gaurav Shah, M.D., Chief Executive Officer and President of Rocket. RP-L301 has the potential to normalize hemoglobin levels, as demonstrated by an increase from an average of 7.4 g/dL (at baseline) to 14.3 g/dL (at 3-months post-treatment) with no transfusion requirements after hematopoietic reconstitution in the first patient treated. This patient exhibited a peripheral blood VCN of 2.21 at 1-month post-treatment, suggesting robust and rapid engraftment. Circulating bilirubin and other markers of hemolysis also normalized. We look forward to progressing the study and presenting longer-term data in the second half of 2021. We remain focused on our mission of relieving suffering for PKD patients who are frequently transfusion-dependent and debilitated from the disease and its treatments.

Key findings from the poster presentation are highlighted below. To access the presentation please visit: https://www.rocketpharma.com/ash-presentations/

Lentiviral Mediated Gene Therapy for Pyruvate Kinase Deficiency: A Global Phase 1 Study for Adult and Pediatric Patients

The data presented in the poster presentation are from two adult patients with significant anemia and transfusion requirement. Patient L301-006-1001 was treated with RP-L301, Rockets ex vivo lentiviral gene therapy candidate for PKD. Patient L301-006-1001 was 31-years old at the time of enrollment and had been followed for 3-months post treatment at the time of data cutoff. Patient L301-001-1002 was 47-years old at the time of enrollment and was recently treated. Key highlights from the presentation include:

Aspects of the RP-L301 pre-clinical data package, including phenotypic reversal in the murine PKD knockout model, were also reviewed.

Conference Call Details Rocket management will host a conference call and webcast on December 7, at 6:00 p.m. EST. To access the call and webcast, please click here. The webcast replay will be available on the Rocket website following the completion of the call.

Investors may listen to the call by dialing (866) 866-1333 from locations in the United States or +1 (404) 260-1421 from outside the United States. Please refer to conference ID number 50038102.

About Pyruvate Kinase Deficiency

Pyruvate kinase deficiency (PKD) is a rare, monogenic red blood cell disorder resulting from a mutation in the PKLR gene encoding for the pyruvate kinase enzyme, a key component of the red blood cell glycolytic pathway. Mutations in the PKLR gene result in increased red blood cell destruction and the disorder ranges from mild to life-threatening anemia. PKD has an estimated prevalence of 3,000 to 8,000 patients in the United States and the European Union. Children are the most commonly and severely affected subgroup of patients. Currently available treatments include splenectomy and red blood cell transfusions, which are associated with immune defects and chronic iron overload.

RP-L301 was in-licensed from the Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER) and Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz (IIS-FJD).

About Rocket Pharmaceuticals, Inc.

Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) (Rocket) is advancing an integrated and sustainable pipeline of genetic therapies that correct the root cause of complex and rare childhood disorders. The companys platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket's clinical programs using lentiviral vector (LVV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, Pyruvate Kinase Deficiency (PKD) a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia and Infantile Malignant Osteopetrosis (IMO), a bone marrow-derived disorder. Rockets first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon disease, a devastating, pediatric heart failure condition. For more information about Rocket, please visit http://www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking Statements

Various statements in this release concerning Rocket's future expectations, plans and prospects, including without limitation, Rocket's expectations regarding its guidance for 2020 in light of COVID-19, the safety, effectiveness and timing of product candidates that Rocket may develop, to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Infantile Malignant Osteopetrosis (IMO) and Danon Disease, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket's ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rockets ongoing trials, our expectations regarding when clinical trial sites will resume normal business operations, our expectations regarding the delays and impact of COVID-19 on clinical sites, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, Rocket's dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020, filed November 6, 2020 with the SEC. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

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Rocket Pharmaceuticals Announces Positive Preliminary Clinical Data from Phase 1 Trial of RP-L301 for the Treatment of Pyruvate Kinase Deficiency at...

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, today announced clinical data from its ongoing multicenter Phase 1 clinical trial of JSP191, a first-in-class anti-CD117 monoclonal antibody, in patients with severe combined immune deficiency (SCID). The trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with SCID who are either transplant-naive or who received a prior stem cell transplant with a poor outcome.

Data from the first transplant-nave SCID patient in the Phase 1 trial, a 6-month-old infant, showed that a single dose of JSP191 administered prior to stem cell transplant was effective in establishing sustained donor chimerism followed by development of B, T and NK immune cells. No treatment-related adverse events were reported. The data were presented by primary investigator Rajni Agrawal-Hashmi, M.D., of Stanford University, at the 62nd American Society of Hematology (ASH) Annual Meeting & Exposition.

We have previously shown that JSP191 can be successfully used as a single conditioning agent in SCID patients who had failed a previous transplant, said Kevin N. Heller, M.D., Executive Vice President, Research and Development, of Jasper Therapeutics. This new data presented at ASH 2020 showing success in an infant with SCID undergoing a first transplant provides proof of concept of the safety and efficacy of the use of JSP191 as an alternative to genotoxic chemotherapies currently used to deplete stem cells prior to transplant.

Hematopoietic cell transplantation offers the only curative therapy for SCID, a severe genetic immune disorder that leaves patients without a functioning immune system. With this approach, standard-of-care chemotherapeutic conditioning regimens are given prior to transplant to reduce the number of blood stem cells in the bone marrow to make space for donor blood stem cells to engraft and cure the patient. JSP191 is designed to replace the need for chemotherapeutic conditioning agents, which are DNA-damaging and highly toxic.

Dr. Heller added, With our Phase 1 trials in SCID and hematologic disorders underway, we are planning to expand the development of JSP191 into additional indications, such as gene therapies, autoimmune diseases, Fanconis anemia and other rare disorders that can be cured by stem cell transplant.

The open-label, multicenter Phase 1 study is evaluating the safety, tolerability and efficacy of JSP191 as a conditioning agent in patients with SCID undergoing first or repeat hematopoietic cell transplantation. Up to three different doses of JSP191 are being assessed for dose-limiting toxicities. The trial is currently open for enrollment at Stanford University, the University of California, San Francisco, Memorial Sloan Kettering Cancer Center, the University of California, Los Angeles, and Cincinnati Childrens Hospital. Additional clinical trial sites in the United States will initiate enrollment in the coming weeks.

About SCID

Severe combined immune deficiency (SCID) is a group of rare disorders caused by mutations in genes involved in the development and function of infection-fighting immune cells. Infants with SCID appear healthy at birth but are highly susceptible to severe infections. The condition is fatal, usually within the first year or two of life, unless infants receive immune-restoring treatments, such as transplants of blood-forming stem cells, gene therapy or enzyme therapy.

About JSP191

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in animal models of SCID, myelodysplastic syndromes (MDS) and sickle cell disease (SCD). Treatment with JSP191 creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients.

JSP191 is currently being evaluated as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for severe combined immunodeficiency (SCID), which is potentially curable only by this type of treatment. JSP191 is also being evaluated in a Phase 1 study in patients with MDS or acute myeloid leukemia (AML) who are receiving hematopoietic cell transplant. For more information about the design of these clinical trials, visit http://www.clinicaltrials.gov (NCT02963064 and NCT04429191). Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The companys lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplant. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. For more information, please visit us at jaspertherapeutics.com.

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Jasper Therapeutics Announces Data from First Transplant-naive Patient in Phase 1 Clinical Trial of JSP191 as Conditioning Agent in Patients with SCID...

NEW YORK, Dec. 8, 2020 /PRNewswire/ --Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") today announced that first-in-human data from the first dose cohort of the Phase 1 portion of the Actimab-A venetoclax Phase 1/2 combination trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) were presented at the 62nd American Society of Hematology (ASH) annual meeting. The poster presentation highlighted results from the first three patients treated with the initial subtherapeutic dose level of 0.5 Ci/kg of Actimab-A and venetoclax.

The enrolled patients had a median of 2 prior therapies (range 2-3) and a median bone marrow blast percentage of 30% (range 20 - >60). All 3 patients had poor risk disease with adverse cytogenetics, and each patient had an additional high-risk marker (FLT3-ITD+, antecedent JAK2+ myelofibrosis, or TP53 mutation). One patient who had multiple genetic mutations including IDH2, RUNX1, TP53 and others, achieved a complete remission with incomplete blood count recovery (CRi) after the first cycle of Actimab-A and venetoclax. Next generation sequencing at the end of the first cycle showed that patient was negative for the known IDH2 and RUNX1 mutations. This patient has continued treatment receiving the second cycle and their bone marrow remains normocellular with no excess blasts. In addition, another patient achieved a partial response after one cycle of Actimab-A and venetoclax. There were no Actimab-A related dose limiting toxicities or nonhematologic Grade 3 or greater related AEs reported in the first cohort. The trial has advanced to the second dose cohort of 1.0 Ci/kg of Actimab-A and venetoclax with patient enrollment ongoing.

Sandesh Seth, Actinium's Chairman and Chief Executive Officer, commented, "This ASH meeting, we are excited to highlight the promising data emerging from both our combination trials with Actimab-A in the R/R AML setting, namely the Actimab-A venetoclax and Actimab-A CLAG-M trials. Particularly compelling is the complete response reported in a patient with complex mutations like TP53 with Actimab-A and venetoclax and the high MRD negativity rate with Actimab-A and CLAG-M. The results clearly demonstrate that a superior clinical effect without adding meaningful toxicity is achievable using Ac-225 ARC's to precisely deliver powerful internal radiation and elicit a potentiating and synergistic treatment effect with chemotherapy and targeted agents. With this clinical validation in hand, we look forward to expanding our ARC combinations with other therapeutic modalities in AML and into additional indications to further establish our leadership position in the field by leveraging our enhanced R&D capabilities including new research facilities and key hires."

Dr. Mark Berger, Actinium's Chief Medical Officer, said, "We were thrilled to report a complete response in the Actimab-A venetoclax combination trial, in addition to the partial response previously highlighted in the abstract. Both responses occurred after just one cycle of a subtherapeutic dose of Actimab-A. These initial results, the one complete response and safety profile to date, support the potential mechanistic synergy of Actimab-A with venetoclax. As a single agent, venetoclax has produced low response rates of 19% in patients with R/R AML1 so we are pleased with the results seen in our first dose cohort. In addition, the clinical data from Actimab-A and Iomab-B presented at this year's ASH demonstrates our strong commitment to addressing the unmet needs of patients with R/R AML with our ARCs as best in class therapeutics, bridge to transplant and targeted conditioning for potentially curable bone marrow transplant. With this in mind, we look forward to guidance on Iomab-B expected from the ad-hoc DMC meeting before year-end."

This Phase 1/2 trial is a multicenter, open label trial of Actimab-A (lintuzumab-Ac225) added to venetoclax for patients with CD33 positive R/R AML. A Phase 2 trial studying Actimab-A as a single agent produced a 69% overall response rate in older unfit patients with newly diagnosed AML.In a poster presentation at the American Association of Cancer Research (AACR) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting MCL-1, a protein shown to mediate resistance to venetoclax. Further, the induction of direct AML cell death via double-stranded DNA breaks by Actimab-A provides a second mechanism for enhancing synergistic potency with venetoclax. Venetoclax is a B-Cell Lymphoma 2 (BCL-2) inhibitor that is jointly developed and marketed by AbbVie and Genentech and is approved for patients with AML, Chronic Lymphocytic Leukemia (CLL), and Small Lymphocytic Leukemia (SLL). Despite its approval in AML, venetoclax has produced low response rates of 19% as a single agent in R/R AML.1 This is due in part to the type of AML, risk factors, and cytogenetics of this patient population. The Phase 2 trial results, together with a synergistic mechanism of action with venetoclax demonstrated in pre-clinical studies, are driving this combination trial with an initial focus on the high unmet needs of R/R patients including those who have relapsed or do not respond to treatment with venetoclax based regimens.

1 Aldosset al. Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia. Haematologica2018.1888094.

About Actinium's CD33 Program

Actinium's CD33 program is evaluating the clinical utility of Actimab-A, an ARC comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as patients with multiple myeloma. The CD33 development program is driven by data from over one hundred treated patients, including a Phase 1/2 trial where Actimab-A produced a remission rate as high as 69% as a single agent. This clinical data is shaping a two-pronged approach for the CD33 program, where at low doses the Company is exploring its use for therapeutic purposes in combination with other modalities and at high doses for use for targeted conditioning prior to bone marrow transplant. Actinium currently has multiple clinical trials ongoing including the Phase 1 Actimab-A CLAG-M and Phase 1/2 Actimab-A venetoclax combination trials and is exploring additional CD33 ARC combinations with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, I-131 apamistamab (Iomab-B) is being studied in the ongoing pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over seventy-five percent enrolled and positive single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. More information on this Phase 3 clinical trial can be found at http://www.sierratrial.com. I-131 apamistamab will also be studied as a targeted conditioning agent in a Phase 1 study with a CD19 CAR T-cell therapy and in a Phase 1/2 anti-HIV stem cell gene therapy with UC Davis. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 130 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc. Website: https://www.actiniumpharma.com/

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

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

Contacts:

Investors:Clayton Robertson Actinium Pharmaceuticals, Inc. [emailprotected]

Hans Vitzthum LifeSci Advisors, LLC[emailprotected](617) 430-9758

SOURCE Actinium Pharmaceuticals, Inc.

http://www.actiniumpharma.com/

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Actinium Reports 67 Percent Overall Response Rate in First Cohort in Actimab-A Venetoclax Combination Trial in Relapsed and Refractory AML at ASH -...

NEW YORK & BRISBANE, Calif.(BUSINESS WIRE) Pfizer Inc. (NYSE: PFE) and Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, today announced updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec (SB-525or PF-07055480), an investigational gene therapy for patients with severe hemophilia A. These data are being presented today at the 62nd American Society for Hematology Annual meeting taking place virtually from December 5th 8th. The oral presentation slides, which include follow-up data up to 85 weeks for the longest treated patient, are available on Sangamos website in the Investors and Media section under Events and Presentations.

All five patients in the high dose 3 x 1013 vg/kg cohort have had at least one year of follow-up and showed sustained factor VIII (FVIII) activity levels, with a group median FVIII activity of 56.9% and a group geometric mean FVIII activity of 70.4% via chromogenic assay from week 9 to 52. Steady-state FVIII activity was achieved for all patients in the 3 x 1013 vg/kg cohort within 9 weeks of treatment with giroctocogene fitelparvovec, with no bleeding events and no FVIII infusions (beyond 3 weeks post-infusion) within the first year. As of the cutoff date of August 31, 2020, one patient had one target joint bleed requiring FVIII therapy, occurring after week 52.

It is promising to see how quickly all five patients in the 3 x 1013 vg/kg cohort achieved steady-state FVIII activity levels, with no bleeding events and no factor usage within the first year and only one target joint bleed after 52 weeks, said Andrew D. Leavitt, MD, Professor of Medicine, University of California, San Francisco, CA, and investigator of the Alta and AFFINE studies. Our focus now is to confirm these exciting findings in the Phase 3 study, and to gather long-term data by following these patients and others in the Phase 3 study over a longer period of time.

Giroctocogene fitelparvovec was generally well tolerated. As previously reported, one patient in the 3 x 1013 vg/kg dose cohort had a treatment-related serious adverse event of hypotension (grade 3) and fever (grade 2), with symptoms of headache and tachycardia, which occurred six hours post-infusion with giroctocogene fitelparvovec, and which fully resolved within 24 hours. No other treatment-related serious adverse events were reported as of the cutoff date. Among the five patients in the 3 x 1013 vg/kg dose cohort, four received corticosteroids for liver enzyme (alanine aminotransferase, ALT) elevations. Three patients had subsequent ALT elevations that responded to corticosteroids. All episodes of ALT elevations fully resolved with oral corticosteroids, and as of the cutoff date no participants were on corticosteroids and no corticosteroid use has been initiated after week 52.

We continue to be encouraged by the findings from this Phase 1/2 study, which now include durable factor VIII expression through one year of follow-up, and we look forward to continuing to follow these patients, said Seng Cheng, Senior Vice President and Chief Scientific Officer of Pfizers Rare Disease Research Unit. With the first patient dosed in the Phase 3 AFFINE study in October 2020, we are on track for a readout from this pivotal Phase 3 trial in 2022, which will allow us to better assess the potential of our gene therapy across a larger sample size.

These latest results demonstrate that this gene therapy may bring clinical benefit to patients and has the potential to serve as an alternative to the burdensome standard of care for patients with hemophilia A, said Bettina Cockroft, M.D., M.B.A, Chief Medical Officer of Sangamo. We look forward to continuing to support our collaboration partners at Pfizer as they conduct the Phase 3 AFFINE study and assess the full potential of this promising therapy.

Pfizer and Sangamo plan to present further follow-up data from the Alta study when all five patients in the 3 x 1013 vg/kg dose cohort have been followed for at least two years.

About the Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging, multicenter clinical trial designed to assess the safety and tolerability of giroctocogene fitelparvovec in patients with severe hemophilia A. The mean age of the 11 male patients assessed across four dose cohorts (91011 vg/kg 2 patients, 2 x 1012 vg/kg 2 patients, 11013 vg/kg 2 patients and 3 x 1013 vg/kg 5 patients) is 30 years (range 18-47 years). After one year of follow-up for all patients in the study, participants will be assessed every 6 months until they enroll into a long-term follow-up study.

About the AFFINE study

The Phase 3 AFFINE (NCT04370054) study is an open-label, multicenter, single arm study to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in more than 60 adult (ages 18-64 years) male participants with moderately severe to severe hemophilia A. Eligible study participants will have completed at least six months of routine FVIII prophylaxis therapy during the lead-in Phase 3 study (NCT03587116) in order to collect pretreatment data for efficacy and selected safety parameters.

The primary endpoint is impact on annualized bleeding rate (ABR) through 12 months following treatment with giroctocogene fitelparvovec. This will be compared to ABR on prior FVIII prophylaxis replacement therapy. The secondary endpoints include FVIII activity level after the onset of steady state and through 12 months following infusion of giroctocogene fitelparvovec.

About giroctocogene fitelparvovec

The U.S. Food and Drug Administration has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to giroctocogene fitelparvovec, which also received Orphan Medicinal Product designation from the European Medicines Agency. Giroctocogene fitelparvovec is being developed as part of a collaboration agreement for the global development and commercialization of gene therapies for hemophilia A between Sangamo and Pfizer. In late 2019, Sangamo transferred the manufacturing technology and the Investigational New Drug (IND) application to Pfizer.

About Hemophilia A

Hemophilia is a genetic hematological rare disease that results in a deficiency of a protein that is required for normal blood clotting clotting factor VIII in hemophilia A. The severity of hemophilia that a person has is determined by the amount of factor in the blood. The lower the amount of the factor, the more likely it is that bleeding will occur which can lead to serious health problems.

Hemophilia A occurs in approximately one in every 5,000-10,000 male births worldwide. For people who live with hemophilia A, there is an increased risk of spontaneous bleeding as well as bleeding following injuries or surgery. It is a lifelong disease that requires constant monitoring and therapy.

About Pfizer Rare Disease

Rare diseases include some of the most serious of all illnesses and impact millions of patients worldwide, representing an opportunity to apply our knowledge and expertise to help make a significant impact on addressing unmet medical needs. The Pfizer focus on rare disease builds on more than two decades of experience, a dedicated research unit focusing on rare disease, and a global portfolio of multiple medicines within a number of disease areas of focus, including rare hematologic, neurologic, cardiac and inherited metabolic disorders.

Pfizer Rare Disease combines pioneering science and deep understanding of how diseases work with insights from innovative strategic collaborations with academic researchers, patients, and other companies to deliver transformative treatments and solutions. We innovate every day leveraging our global footprint to accelerate the development and delivery of groundbreaking medicines and the hope of cures.

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PFIZER AND SANGAMO ANNOUNCE UPDATED PHASE 1/2 RESULTS SHOWING SUSTAINED FACTOR VIII ACTIVITY LEVELS IN 3X10 VG/KG COHORT THROUGH ONE YEAR FOLLOWING...

CAMBRIDGE, Mass. and EMERYVILLE, Calif., Dec. 3, 2020 /PRNewswire/ --Tevard Biosciences, a privately-held biotechnology company pioneering tRNA-based gene therapies, and Zogenix (Nasdaq: ZGNX), a global biopharmaceutical company developing and commercializing rare disease therapies, today announced that the companies have entered into a collaboration to identify and develop novel tRNA-based gene therapies for Dravet syndrome and other genetic epilepsies.

Under the collaboration, Tevard will utilize its two unique tRNA-based discovery platforms focused on mRNA Stabilization and Nonsense Codon Suppression to discover and advance novel drug candidates for the treatment of Dravet syndrome and other genetic epilepsies. Zogenix will further develop the candidates through advanced preclinical studies and clinical development, and be responsible for worldwide commercialization.

Zogenix is responsible for funding the collaboration and, under the terms of the agreement, Tevard will receive an initial collaboration payment of $10 million, of which approximately $5 million has previously been paid by Zogenix. Tevard will also receive $5 million in the form of a convertible note. Tevard is also eligible to receive additional development, regulatory and commercial-related milestone payments ranging from $70 million to $100 million for each program, as well as tiered royalties on future net global sales on any commercial products that result from the collaboration.

Tevard's unique tRNA technology platforms are designed to address underlying genetic mutations in a precise and regulated manner through the correction of nonsense mutations and the enhanced production of functional proteins. Together, these approaches hold promise to treat genetic disorders that are not well-suited to conventional gene replacement approaches.

"We are pleased to announce our collaboration with Zogenix, whose commitment to developing new treatments for Dravet syndrome and other genetic epilepsies is unparalleled," said Daniel E. Fischer, Co-founder, President, and Chief Executive Officer at Tevard Biosciences. "Tevard has assembled a team of leading experts focused on developing our breakthrough tRNA-based gene therapy platforms. Our collaboration with Zogenix will advance our mission to bring transformative gene therapy products to those living with Dravet and other rare and severe genetic disorders.

"We are thrilled to be working with an innovative company like Tevard to develop promising next-generation therapies," said Stephen J. Farr, Ph.D., President and Chief Executive Officer of Zogenix. "Through this important new collaboration, we have reinforced our long-term commitment to transforming the lives of rare epilepsy patients and their families, and look forward to sharing updates as our work together progresses."

About Dravet SyndromeDravet syndrome is a rare childhood-onset epilepsy marked by frequent debilitating seizures, lifelong developmental and motor impairments, and an increased risk of death (SUDEP). In addition to the catastrophic impact on the patient, the severity and unpredictability of the seizures, coupled with around-the-clock concern for the diagnosed child's safety and well-being, can present significant emotional and logistical challenges for parents and all members of the family.

About Tevard BiosciencesTevard Biosciences is a privately held biotechnology companypioneering tRNA-based gene therapiesto cure rare and severe genetic diseases with limited or no approved treatment options. Tevard was founded by MIT Professor and Whitehead InstituteFoundingMember Harvey Lodish, Ph.D., with life science entrepreneurs and executives Daniel Fischer and Warren Lammert, fathers of children with Dravet syndrome. The company is developing and applying two novel tRNA-based gene therapy platforms, co-invented by Professor Lodish with Johns Hopkins School of Medicine Professor Jeff Coller, Ph.D. and University of Iowa Professor Chris Ahern, Ph.D., for Dravet syndrome and other rare diseases caused by haploinsufficiency and/or nonsense mutations that are not amenable to traditional approaches to gene therapy. For more information, please visitwww.tevard.com.

About ZogenixZogenix is a global biopharmaceutical company committed to developing and commercializing therapies with the potential to transform the lives of patients and their families living with rare diseases. The company's first rare disease therapy, FINTEPLA (fenfluramine) oral solution has been approved by the U.S. FDA and received a positive CHMP opinion in Europe for the treatment of seizures associated with Dravet syndrome, a rare, severe childhood onset epilepsy. The company has two additional late-stage development programs underway: one for FINTEPLA for the treatment of seizures associated with Lennox-Gastaut syndrome, a different rare childhood-onset epilepsy and another for MT1621, an investigational novel substrate enhancement therapy for the treatment of TK2 deficiency, a rare genetic disorder. MT1621 is being developed through Modis Therapeutics, a Zogenix company.

Forward Looking Statements Zogenixcautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "intends," "potential," "suggests," "assuming," "designed," and similar expressions are intended to identify forward-looking statements. These statements include the potential that the use tRNA-based discovery platforms will result in the discovery and advancement novel drug candidates for the treatment of genetic epilepsies; and Zogenix's intention to develop any drug candidates discovered through tRNA-based discovery platforms. These statements are based on Zogenix's current beliefs and expectations. The inclusion of forward-looking statements should not be regarded as a representation byZogenixthat any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in Zogenix's business, including, uncertainties related to pharmaceutical product development, including whether any drug candidate will be discovered; results from preclinical or clinical studies may not support the continued development or commercialization of any discovered drug candidate; delays or disruptions in Zogenix's or Tevard's business operations due to the COVID-19 pandemic and other risks described in Zogenix's prior press releases as well as in public periodic filings with theU.S. Securities & Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, andZogenixundertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

CONTACTS:

Tevard BiosciencesInvestors and MediaKaren L. Bergman for Tevard+1 (650) 575-1509[emailprotected]

ZogenixMelinda BakerSenior Director, Corporate Communications+1 (510) 788-8732[emailprotected]

InvestorsBrian RitchieManaging Director, LifeSci Advisors LLC+1 (212) 915-2578[emailprotected]

MediaStefanie TuckVice President, Porter Novelli+1 (978) 390-1394[emailprotected]

SOURCE Tevard Biosciences

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Tevard Biosciences and Zogenix Announce Collaboration to Advance Novel Gene Therapies for Dravet Syndrome and Other Genetic Epilepsies - PRNewswire