On November 6, 2019 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO) reported that it is offering to sell, subject to market and other conditions, up to 7.5 million shares of its common stock in an underwritten public offering (Press release, Agios Pharmaceuticals, NOV 6, 2019, View Source [SID1234550434]). Agios also intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of common stock sold in the public offering. All of the shares in the offering are to be sold by Agios. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed.

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J.P. Morgan Securities LLC, Goldman Sachs & Co. LLC and Cowen and Company, LLC are acting as joint book-running managers for the offering.

The shares are being offered by Agios pursuant to an automatically effective shelf registration statement that has been filed with the Securities and Exchange Commission ("SEC"). The offering is being made only by means of a prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement relating to, and describing the terms of, the offering will be filed with the SEC and will be available on the SEC’s web site at www.sec.gov.

Copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering can be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, telephone: 866-803-9204; Goldman Sachs & Co. LLC, Attn: Prospectus Department, 200 West Street, New York, New York 10282, telephone: 866-471-2526, facsimile: 212-902-9316, e-mail: [email protected]; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department, by email at [email protected], or by telephone at (833) 297-2926. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the SEC.

This press release does not constitute an offer to sell or the solicitation of an offer to buy, 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 registration or qualification under the securities laws of any such state or jurisdiction.

On November 6, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that 15 abstracts featuring clinical and translational data from its oncology and rare genetic diseases programs will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 7-10, 2019 in Orlando (Press release, Agios Pharmaceuticals, NOV 6, 2019, View Source [SID1234550433]).

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The accepted abstracts are listed below and are available online on the ASH (Free ASH Whitepaper) conference website: View Source

Oral Presentations

Abstract #541: Complex Polyclonal Resistance Mechanisms to Ivosidenib Monotherapy in IDH1-Mutant Relapsed or Refractory Acute Myeloid Leukemia Revealed By Single Cell Sequencing Analyses
Date & Time: Monday, December 9, 2019 at 7:00 a.m. ET
Oral Abstract Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Single-Cell and Clonal Approaches to Treatment Resistance in AML
Location: Orange County Convention Center, Valencia A (W415A)
Presenter: Hongfang Wang, Ph.D., Agios Pharmaceuticals

Abstract #545: Molecular Mechanisms Mediating Relapse Following Ivosidenib Monotherapy in Patients with IDH1-Mutant Relapsed or Refractory Acute Myeloid Leukemia
Date & Time: Monday, December 9, 2019 at 8:00 a.m. ET
Oral Abstract Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Single-Cell and Clonal Approaches to Treatment Resistance in AML
Location: Orange County Convention Center, Valencia A (W415A)
Presenter: Sung Choe, Ph.D., Agios Pharmaceuticals

Abstract #643: Enasidenib Plus Azacitidine Significantly Improves Complete Remission and Overall Response Compared with Azacitidine Alone in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) with Isocitrate Dehydrogenase 2 (IDH2) Mutations: Interim Phase II Results from an Ongoing, Randomized Study
Date & Time: Monday, December 9, 2019 at 10:30 a.m. ET
Oral Abstract Session: 613. Acute Myeloid Leukemia: Clinical Studies: Non-Intensive Therapy
Location: Orange County Convention Center, Valencia A (W415A)
Presenter: Courtney DiNardo, M.D., University of Texas MD Anderson Cancer Center

Poster Presentations

Abstract #2175: Comorbidities and Complications in Adults with Pyruvate Kinase Deficiency
Poster Session Date & Time: Saturday, December 7, 2019 from 5:30-7:30 p.m. ET
Poster Session: 904. Outcomes Research – Non-Malignant Conditions: Poster II

Abstract #1570: Hematologic Malignancies Exhibit Selective Vulnerability to Inhibition of De Novo Pyrimidine Biosynthesis By AG-636, a Novel Inhibitor of Dihydroorotate Dehydrogenase in Phase 1 Clinical Trials
Poster Session Date & Time: Saturday, December 7, 2019 from 5:30-7:30 p.m. ET
Poster Session: 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Poster I

Abstract #1286: AG-636 for the Treatment of Adults with Advanced Lymphoma: Initiation of a Phase 1 Clinical Study
Poster Session Date & Time: Saturday, December 7, 2019 from 5:30-7:30 p.m. ET
Poster Session: 605. Molecular Pharmacology, Drug Resistance – Lymphoid and Other Diseases: Poster I

Abstract #2223: An Ongoing Global, Longitudinal, Observational Study of Patients with Pyruvate Kinase Deficiency: The PEAK Registry
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster II

Abstract #2249: Mitapivat (AG-348), an Oral PK-R Activator, in Adults with Non-Transfusion Dependent Thalassemia: A Phase 2, Open-Label, Multicenter Study in Progress
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 112. Thalassemia and Globin Gene Regulation: Poster II

Abstract #3447: Development of Patient-Reported Outcome Measures (Symptoms and Impacts) in Adults with Pyruvate Kinase Deficiency
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 904. Outcomes Research – Non-Malignant Conditions: Poster II

Abstract #2593: AGILE: A Phase 3, Multicenter, Double‐Blind, Randomized, Placebo‐Controlled Study of Ivosidenib in Combination with Azacitidine in Adult Patients with Previously Untreated Acute Myeloid Leukemia with an IDH1 Mutation
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II

Abstract #2706: High Rate of IDH1 Mutation Clearance and Measurable Residual Disease Negativity in Patients with IDH1-Mutant Newly Diagnosed Acute Myeloid Leukemia Treated with Ivosidenib (AG-120) and Azacitidine
Poster Session Date & Time: Sunday, December 8, 2019 from 6:00-8:00 p.m. ET
Poster Session: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II

Abstract #3512: Long-Term Safety and Efficacy of Mitapivat (AG-348), a Pyruvate Kinase Activator, in Patients with Pyruvate Kinase Deficiency: The DRIVE PK Study
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III

Abstract #3526: Mitapivat (AG-348) in Adults with Pyruvate Kinase Deficiency Who Are Regularly Transfused: A Phase 3, Open-Label, Multicenter, Study (ACTIVATE-T) in Progress
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III

Abstract #3513: Prevalence of Pyruvate Kinase Deficiency: A Systematic Literature Review
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III

Abstract #4254: Ivosidenib (AG-120) in Patients with IDH1-Mutant Relapsed/Refractory Myelodysplastic Syndrome: Updated Enrollment of a Phase 1 Dose Escalation and Expansion Study
Poster Session Date & Time: Monday, December 9, 2019 from 6:00-8:00 p.m. ET
Poster Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster III

Event and Webcast Information
Agios will host an investor event on December 9, 2019 at 8:00 p.m. ET in Orlando to review the data from the company’s oncology and rare genetic diseases programs. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

On November 6, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that interim results from a Phase 1 trial studying Actimab-A in combination with CLAG-M have been accepted for presentation at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting that is being held December 7-10, 2019 in Orlando, FL (Press release, Actinium Pharmaceuticals, NOV 6, 2019, View Source [SID1234550432]). This is the first study to combine radioimmunotherapy and intensive chemotherapy in patients with relapsed or refractory AML. Actimab-A is an antibody radiation-conjugate (ARC) comprised of the CD33 targeting antibody lintuzumab labeled with the alpha-emitting radioisotope actinium-225 (Ac-225).

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The ASH (Free ASH Whitepaper) abstract reports on 9 adult patients with relapsed or refractory AML enrolled on the investigator-initiated trial at the Medical College of Wisconsin (MCW). Patients were a median age of 59 and had received a median of 2 (range 1-4) anti-leukemic treatments, including 4 patients who relapsed after receiving a bone marrow transplant (BMT). Patients received the salvage chemotherapy regimen cladribine, cytarabine, G-CSF, and mitoxantrone (CLAG-M) and a single dose of Actimab-A on either day 6, day 7, or day 8. Cohort 1 enrolled 3 patients who received 0.25 uCi/kg of Actimab-A and Cohort 2 enrolled 6 patients who received 0.50 uCi/kg of Actimab-A.

Details and highlights from Actinium’s accepted poster include:

Title: Lintuzumab Ac-225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML: Interim Results of a Phase I Study

Key Highlights:

83% of patients (5/6) receiving 0.50 uCi/kg of Actimab-A and CLAG-M in the second dosing cohort achieved a Complete Remission (CR), Complete Response with incomplete platelet recovery (CRp) or Complete Response with incomplete hematologic recovery (CRi)
83% remission rate with 0.50 uCi/kg Actimab-A CLAG-M combination significantly higher than the MCW institutional 54% remission rate with CLAG-M alone1
83% remission rate at 0.50 uCi/kg included 50% (3/6) with a CR
33% of patients (3/9) enrolled in the trial subsequently received a bone marrow transplant
Combining lower doses of Actimab-A with CLAG-M appears to have a clinically acceptable safety profile
All patients completed the planned cycle of Actimab-A and CLAG-M
No mortalities were observed on study
Poster Details:
Publication Number: 2605
Session Name: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II
Date: Sunday, December 8, 2019
Presentation Time: 6:00 PM – 8:00 PM
Location: Orange County Convention Center, Hall B

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "It is quite encouraging to see a high overall response rate with the addition of Actimab-A compared to patients treated with CLAG-M alone. These preliminary results exceed our expectations and compare quite favorably to results seen with recently approved AML therapies, especially in these difficult to treat relapsed or refractory patients. We look forward to seeing additional results from this trial and are excited by the potential to advance the Actimab-A CLAG-M combination to a Phase 2 or potentially pivotal trial. In addition, the ability to combine Actimab-A with a powerful salvage regimen like CLAG-M with a manageable adverse event profile suggests that combinations with other agents, such as venetoclax, may also be tolerable and will lead to improved efficacy."

Sandesh Seth, Actinium’s Chairman and CEO, said, "These results strengthen our conviction in the potentiating and synergistic properties of targeted radiation with other therapeutic modalities. We see opportunities to combine our ARCs with chemotherapy as highlighted in this study, with targeted agents as we have done with our Actimab-A venetoclax combination trial and potentially with immunotherapy. Additionally, the rate of patients going to transplant in this study, despite the low dose levels of Actimab-A administered, gives us great excitement for our Actimab-MDS program that will study significantly higher doses of Actimab-A as a targeted conditioning regimen prior to a bone marrow transplant in patients with high-risk MDS. It is exciting to see our CD33 program development strategy with low-dose combinations and high-dose targeted conditioning generate positive responses and we look forward to additional data from our ongoing and planned clinical trials."

About Actimab-A

Actimab-A (actinium-225 lintuzumab) is an antibody radiation-conjugate that has been studied in over 100 patients in 4 clinical trials at several dose levels. 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. The findings from this study are supporting a development strategy that will study Actimab-A at high doses for targeted conditioning prior to bone marrow transplant in the planned pivotal Actimab-MDS program, and at lower doses in combination with other therapeutic modalities like the combination trial with the Bcl-2 inhibitor venetoclax and the combination trial with the chemotherapy regimen CLAG-M.

On November 6, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported that new findings from its pivotal Phase 3 SIERRA trial for Iomab-B (Iodine-131 apamistamab) that support its Iomab-ACT program for lymphodepletion for CAR-T and adoptive cell therapies has been accepted for presentation at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting that is being held December 7-10, 2019 in Orlando, FL (Press release, Actinium Pharmaceuticals, NOV 6, 2019, View Source [SID1234550431]). Lymphodepletion is a necessary step that creates space for the CAR-T cells to be infused and promotes expansion of cells in vivo by creating a favorable homeostatic cytokine environment. Actinium is advancing the development of low dose Iomab-B (Iodine-131 apamistamab), a CD45 targeting antibody radiation-conjugate (ARC), as an alternative to today’s standard practice of chemotherapy-based lymphodepletion regimens like fludarabine/cyclophosphamide (Flu/Cy), which have been implicated in CAR-T toxicities including cytokine release syndrome (CRS) and neurotoxicity.

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Title: Sierra Clinical Trial Dosimetry Results Support Low Dose Anti-CD45 Iodine (131I) Apamistamab [Iomab-B] for Targeted Lymphodepletion Prior to Adoptive Cell Therapy

An analysis was performed on blood samples from 57 patients enrolled in the ongoing pivotal Phase 3 SIERRA trial for Iomab-B to demonstrate the effectiveness of low dose Iomab-B as a modality for targeted transient lymphodepletion. On the SIERRA trial, patients receive a low dosimetry dose of Iomab-B (median dose of 10 mCi with a range of 7-20 mCi) in an outpatient setting per study protocol. The analysis presented in the poster evaluated blood samples at various time points including pre-dosimetric infusion, post-dosimetric infusion, day 1 post-dosimetric infusion, and pre-therapeutic infusion (range 6-14 days post-dosimetry) to assess the impact of low dose Iomab-B on immune cell lymphodepletion and its anti-tumor effect on circulating blasts, as well as to determine its clearance profile from circulation.

Key Highlights:

– A significant but transient reduction in lymphocytes and white blood cells was observed compared to pre-dosimetry infusion levels
– 85% reduction in lymphocytes was observed at the post-dosimetry infusion time point, a 67% decrease at day 1 post-dosimetric infusion, and a 43% decrease one week later just prior to the Iomab-B therapeutic infusion
– 35% reduction in peripheral leukemic blasts was observed at the post-dosimetry infusion time point, suggesting a rapid anti-leukemic effect with single-agent Iomab-B consistent with findings from SIERRA presented at ASCO (Free ASCO Whitepaper) 2019
– The levels of platelets, red blood cells, and neutrophils were unchanged between pre-infusion and post-dosimetry infusion, potentially reflecting the comparatively lower surface antigen levels of CD45 on these cell types
– Based on an analysis of 25 treated patients, a non-myeloablative dose of 75 mCi has been proposed as a starting dose for human clinical testing
– Analysis of the proposed 75 mCi dose of Iomab-B would be sufficiently cleared in 136 hours (5.7 days) to allow for CAR-T administration

Poster Details:

Publication Number: 1958
Session Name: 704. Immunotherapies: Poster I
Date: Saturday, December 7, 2019
Presentation Time: 5:30 PM – 7:30 PM
Location: Orange County Convention Center, Hall B

Dale Ludwig, Ph.D., Actinium’s Chief Scientific Officer, said, "These promising findings from the analysis of clinical data from the SIERRA trial confirm our excitement and support the potential of our Iomab-ACT program as a chemotherapy-free alternative for lymphodepletion. While significant efforts have gone towards innovating CAR-T and cellular therapies, there has been little innovation in the lymphodepletion regimens that they rely on. These results show that the multi-modal mechanism of our CD45 targeting ARC can selectively deplete immune cells and exert an anti-leukemic effect while sparing red blood cells and platelets through a single-dose outpatient administration. It is exciting to see human clinical data produce these promising results and demonstrate that our Iomab-ACT program will fit well within the vein-to-vein time of CAR-T. We look forward to beginning a first-in-man clinical trial that will explore our Iomab-ACT program in conjunction with a CAR-T therapy and we have great confidence in continued positive results."

About the Iomab-ACT program

Iomab-ACT is a lower dose of Actinium’s lead program Iomab-B, which has been studied in over 300 patients and is currently being investigated in a pivotal Phase 3 trial for targeted conditioning prior to a Bone Marrow Transplant (BMT). Iomab-ACT targets CD45, an antigen expressed on many of the cells that are relevant to CAR-T including lymphocytes, macrophages and regulatory T-cells and that have been associated with CAR-T challenges such as durability of response, cytokine release syndrome (CRS) and neurotoxicity. Actinium has generated preclinical data that targeted lymphodepletion via Iomab-ACT has the potential to improve tumor control, selectively deplete necessary cells and be highly differentiated in terms of tolerability compared to chemotherapy-based lymphodepletion regimens, namely fludarabine/cyclophosphamide (Flu/Cy). The Iomab-ACT program may enable lymphodepletion through a single-dose outpatient administration versus Flu/Cy or other chemo-based lymphodepletion regimens that require multiple infusions in an inpatient setting over several days.

On November 6, 2019 AbbVie Inc. (NYSE:ABBV) ("AbbVie") reported that it has launched a private offering (the "Offering") of senior unsecured notes (the "Notes") (Press release, AbbVie, NOV 6, 2019, View Source [SID1234550430]).

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The Offering is being conducted in connection with AbbVie’s previously announced acquisition (the "Acquisition") of Allergan plc ("Allergan"). AbbVie expects to use the net proceeds from the Offering to fund a portion of the aggregate cash consideration due to Allergan shareholders in connection with the Acquisition and to pay related fees and expenses, with any remaining net proceeds being used for general corporate purposes. Consummation of the Offering is subject to market and other conditions.

The Notes have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), any state securities laws or the securities laws of any other jurisdiction, and may not be offered or sold in the United States, or for the benefit of U.S. persons, except pursuant to an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities or blue sky laws. Accordingly, the Notes are being offered in the United States only to persons reasonably believed to be "qualified institutional buyers," as that term is defined under Rule 144A of the Securities Act, or outside the United States to non-"U.S. persons" in accordance with Regulation S under the Securities Act.

A confidential offering memorandum for the Offering of the Notes, dated as of today, is being made available to such eligible persons. The Offering is being conducted in accordance with the terms and subject to the conditions set forth in such confidential offering memorandum.

This news release does not constitute an offer to sell or purchase, or a solicitation of an offer to sell or purchase, the Notes or any other security. No offer, solicitation, purchase or sale will be made in any jurisdiction in which such an offer, solicitation or sale would be unlawful.