On June 28, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN:ATNM) ("Actinium" or "the Company"), reported that Dr. Joseph Jurcic, Director of the Hematologic Malignancies Section and Professor of Medicine at Columbia University Medical Center, has initiated Actimab-A MRD, a new clinical trial for patients with AML who are in remission but have detectable minimal residual disease (MRD) (Press release, Actinium Pharmaceuticals, JUN 28, 2018, View Source [SID1234527514]). The trial will study the safety/tolerability of Actimab-A in the postremission consolidation setting and include dose finding analyses. The trial will also study the impact of Actimab-A on minimal residual disease (MRD) as well as progression-free (PFS) and overall survival (OS) rates. The investigational new drug (IND) application for this trial has been cleared by the FDA.

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Together with Dr. Jurcic, Actinium will host a webcast to discuss the planned trial, participation information is as follows:

Date: July 10, 2018
Time: 8:00 AM ET
Registration Link: View Source
Telephone participation: U.S./Canada Toll Free: (855) 427-0225 or (718) 865-8336
Conference ID: 2540

Dr. Joseph Jurcic said, "Although patients with AML can achieve complete remissions with induction therapy, the rate of relapse remains high resulting in high mortality rates. Strong evidence exists that minimal residual disease is a major driver of disease relapse and clearly demonstrates the need for improved consolidation therapies that can effectively target MRD. Based on the clinical profile of Actimab-A to date, I am excited to study this therapy for use as a consolidation therapy. It will be a significant advancement for AML patients if this trial shows the ability to target MRD and reduce relapse rates."

There are an estimated 21,000 patients diagnosed with AML annually in the United States and over 350,000 cases of AML worldwide. According to the National Cancer Institute, 5-year survival for AML patients under age 65 is 45% while 5-year survival for patients over 65 is 6% with the median age of diagnosis of AML patients being 68. With curative intent induction chemotherapy, 45% – 65% of patients can achieve complete remission but up to 80% of patients will relapse despite postremission consolidation treatment. Currently, non-transplant-based consolidation therapies consist mainly of chemotherapy such as high-dose Cytarabine. The presence of MRD has been shown to be associated with higher rates of relapse and earlier relapse in multiple studies. Recently, the FDA approved a therapy for patients with a certain type of B-cell leukemia who are in remission but have detectable MRD.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "Actimab-A has many points of differentiation that I feel make it well suited to address MRD treatment as consolidation therapy. Given that patients receive chemotherapy as induction therapy, I believe it is important to develop a non-chemotherapy based consolidation therapy that has fewer toxicities and side effects than chemotherapy. This is particularly important for older patients, who do not have the same ability to tolerate high dose therapies as young patients, and who are the majority of patients with AML. We believe our ARC or Antibody Radiation Conjugate approach enables precision targeting of residual AML cells and potentially provide a means by which MRD can be eliminated and relapse rates lowered. We look forward to working with Dr. Jurcic to execute this important trial for AML patients."

Sandesh Seth, Actinium’s Chairman and CEO said, "We are excited by the continued expansion of our CD33 program and intend to solidify our position as the best-in-class CD33 targeting therapy by demonstrating its potential in multiple diseases and multiple indications. Expansion into the consolidation setting is an important achievement towards this end. Further, the application of our therapy for MRD, strategically aligns us with the forefront of scientific exploration in a clinical setting. We believe the breadth of our CD33 program is unmatched given that we are now studying our ARC not only in multiple AML settings including induction, consolidation and in relapsed/refractory disease but also in multiple myeloma as a therapeutic, and in MDS as targeted conditioning to enable a bone marrow transplant. With this important trial poised to start and clinical data expected from our ongoing trials, we are confident in our ability to realize the intrinsic value of this program and advance these trials to benefit the greatest number of patients."

About Actimab-A
Actimab-A is an antibody radio-conjugate (ARC) comprised of the anti-CD33 monoclonal antibody lintuzumab labeled with the radioisotope actinium-225. CD33 is a marker expressed on AML cells of virtually all affected patients. Actimab-A has been studied in over 100 patients to date and is the only CD33 targeting agent being studied in a broad range of diseases in which the CD33 antigen is expressed, including AML, myelodysplastic syndrome (MDS) and multiple myeloma.

Actinium-225 is highly differentiated radioisotope that emits high amounts of energy through the release of four alpha-particles that can cause double-stranded breaks in DNA with known resistance mechanisms to Actinium-225. Given the limited distance of its energy in the body, it is potentially sparing of non-targeted cells leading to better tolerability and less toxicities.

Actimab-A has been granted Orphan Drug Designation from both the U.S. Food and Drug Administration and the European Medicines Agency for newly diagnosed AML in patients age 60 and above.

On June 28, 2018 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of precisely targeted oncology therapies, reported publication of results of preclinical studies of CPI-444 conducted by researchers at Johns Hopkins University School of Medicine (Press release, Corvus Pharmaceuticals, JUN 28, 2018, View Source;p=RssLanding&cat=news&id=2356398 [SID1234527496]). The data showed that CPI-444 administered as monotherapy suppressed tumor growth and improved survival in animal tumor models, and CPI-444 administered in combination with anti-PD-1 therapy dramatically improved antitumor immune responses over either agent used alone. The results were published online this month in the journal Cancer Immunology, Immunotherapy (CII), in a publication titled "Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT (adoptive cellular therapy) in murine cancer models," and can be accessed here.

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CPI-444, Corvus’ lead product candidate, is a selective and potent inhibitor of the adenosine A2A receptor. It is currently being evaluated in early-stage clinical trials in patients with various solid tumors as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody.

"These newly published studies add to the growing scientific and clinical evidence of the importance of the adenosine pathway in modulating immune responses in cancer. The results provide further evidence that the A2A receptor may serve as a crucial regulator of immune response, and confirms the potential of CPI-444 in cancer therapy," said Richard A. Miller, M.D., an oncologist and co-founder, president and chief executive officer of Corvus. "CPI-444 has been studied in more than 250 patients to date both as a monotherapy and in combination with an anti-PD-L1 antibody. To our knowledge, it is the only A2A receptor antagonist to reproducibly show anti-tumor activity as a monotherapy in preclinical and clinical studies. We are currently enrolling patients in a Phase 1/1b trial in renal cell cancer and in a Phase 1b/2 trial in non-small cell lung cancer."

Results of the preclinical studies conducted by researchers at the Sidney Kimmel Comprehensive Cancer Research Center and Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, showed that CPI-444:

Administered as monotherapy suppressed tumor growth and improved survival in two animal models of colon tumors — CT26, which is very resistant to checkpoint blockade, and MC38.
Enhanced the efficacy of anti-PD-1 immunotherapy. The combination therapy dramatically improved tumor regression and animal survival in both the CT26 and MC38 colon tumor models. The effect was particularly marked in the CT26 tumor model, which showed a 70 percent cure rate.
Dramatically enhanced immune responses in models of tumor immunity, augmented immune memory responses to viral antigens, and enhanced adoptive cellular therapy (ACT) in an animal model of melanoma.
Suppressed the expression of multiple checkpoint pathways, including PD-1, LAG-3, TIM-3 and CTLA-4, on both CD8 positive and T reg cells (which play an important role in regulating antitumor immune responses). The most significant effects were seen in tumor-draining lymph nodes.
Increased the function of killer T cells (CD8+) in tumor infiltrating cells.
ABOUT CPI-444
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic.

On June 27, 2018 Purdue Pharma L.P. reported successful completion of a first-in-human Phase 1 dose escalation study of tinostamustine in patients with relapsed or refractory hematological malignancies for which there are no available therapies (Press release, Purdue Pharma, JUN 27, 2018, View Source [SID1234527497]). The study evaluated the safety and pharmacokinetics, and sought to determine the maximum tolerated dose and inform a Phase 2 dose of tinostamustine. 1

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The multi-acting therapy candidate tinostamustine, previously known as EDO-S101, is a novel and potentially first-in-class alkylating deacetylase inhibitor (AK-DACi) therapy being studied for its potential to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage. It is in development for a range of rare or difficult to treat blood cancers and solid tumors. Based on the results of this Phase I human trial, Purdue will support advancement of tinostamustine into further clinical studies.

"We are pleased with the outcome of this promising early stage oncology program and we believe it has the potential to make meaningful clinical contributions in areas with significant unmet needs," said Craig Landau, MD, president and CEO, Purdue Pharma. "In addition to our established commitments in oncology and neuroscience, we are actively seeking opportunities to collaborate across a number of therapeutic areas as part of our ongoing efforts to diversify our scientific research and bring therapies to market that may improve outcomes for patients."

The reported completion of this study is the first clinical update since Purdue announced in November 2017 significant oncology-related investments to establish a portfolio of drug candidates with the potential to deliver new cancer therapies, in areas of high unmet medical need, to physicians and patients. As part of these investments, Purdue is currently supporting research for four drug candidates across 14 different cancer types. Research on these compounds is being advanced on behalf of Purdue by Mundipharma EDO.

In addition to tinostamustine, Purdue’s clinical stage oncology portfolio includes etoposide toniribate, a novel target-activated topoisomerase inhibitor that delivers the chemotherapy etoposide to tumors in an inactive form where it is ‘switched on’ by enzymes called carboxylesterases. Purdue also has two late pre-clinical stage antibody-drug conjugates, EDO-B776 and EDO-B278, in development. EDO-B776 is being studied for its potential to target the cancer antigen 125 (CA-125) in ovarian cancer. EDO-B278, which targets human tissue factor, is in development for treatment of various solid tumors.

The decision to move tinostamustine into Phase 1 human trials was supported by preclinical studies, which suggest that tinostamustine may deliver both alkylating activity and pan-histone deacetylase (HDAC) inhibition to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage.

Purdue will also continue to selectively seek additional oncology product assets through licensing and acquisition, and the company will maintain a priority interest in candidates with mechanisms complementary to emerging immuno-oncology based treatment paradigms

On June 27, 2018 Forty Seven, Inc. (Nasdaq:FTSV), a clinical stage immuno-oncology company, reported the pricing of its initial public offering of 7,035,000 shares of common stock at a price to the public of $16.00 per share (Press release, Forty Seven, JUN 27, 2018, View Source [SID1234527522]). In addition, Forty Seven has granted the underwriters a 30-day option to purchase up to an additional 1,055,250 shares of common stock solely to cover over-allotments, if any, at the initial public offering price less underwriting discounts and commissions. The shares are expected to begin trading on The Nasdaq Global Select Market under the symbol "FTSV" on June 28, 2018.

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Morgan Stanley and Credit Suisse are acting as lead bookrunners, Canaccord Genuity is acting as lead manager, and BTIG and Oppenheimer & Co. Inc. are acting as co-managers for the offering.

The offering is being made only by means of a prospectus. A copy of the final prospectus, when available, may be obtained from Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, Second Floor, New York, New York 10014; or Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, One Madison Avenue, New York, New York, 10010 or by email at [email protected].

A registration statement relating to these securities has been filed with, and declared effective by, the Securities and Exchange Commission. This press release shall 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 June 27, 2018 AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) reported positive results from the randomised, double-blinded, placebo-controlled, Phase III SOLO-1 trial of Lynparza (olaparib) tablets (Press release, AstraZeneca, JUN 26, 2018, View Source [SID1234527478]).

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Women with BRCA-mutated (BRCAm) advanced ovarian cancer treated 1st-line with Lynparza maintenance therapy had a statistically-significant and clinically-meaningful improvement in progression-free survival compared to placebo. The safety and tolerability profile of Lynparza was consistent with previous trials. Based upon these data, AstraZeneca and MSD plan to initiate discussions with health authorities regarding regulatory submissions.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "For the first time, we see a significant and clinically-impactful improvement in progression-free survival in the 1st-line maintenance setting for women with BRCA-mutated ovarian cancer treated with a PARP inhibitor. The SOLO-1 data reinforce the importance of knowing BRCA status at diagnosis, as this may enable women with BRCA-mutated ovarian cancer to receive Lynparza earlier. We would like to thank the investigators, hospitals and most of all the patients who took part in this trial, without whom medical advancements would not be possible."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Building on the strong data we’ve seen with Lynparza to date, the data from SOLO-1 reinforces Lynparza’s ability to provide meaningful disease control with a well-characterised safety and tolerability profile. We look forward to presenting the full data set for SOLO-1 at a future medical meeting and working with regulatory authorities to bring Lynparza to women with ovarian cancer in the 1st-line maintenance setting as quickly as possible."

Additionally, the ongoing GINECO/ENGOTov25 Phase III trial, PAOLA-1, is testing the effect of Lynparza in combination with bevacizumab as a 1st-line maintenance treatment in women with newly-diagnosed advanced ovarian cancer, regardless of their BRCA status. Results are expected in 2019.

NOTES TO EDITORS
About SOLO-1

SOLO-1 is a Phase III randomised, double-blinded, placebo-controlled, multicentre trial to evaluate the efficacy and safety of Lynparza tablets as 1st-line maintenance monotherapy compared with placebo, in patients with BRCAm advanced ovarian cancer. The trial randomised 391 patients with a deleterious or suspected deleterious BRCA1 or BRCA2 mutation who were in clinical complete or partial response following platinum-based chemotherapy. Eligible patients were randomised (2:1) to receive Lynparza 300mg tablets twice daily or placebo tablets twice daily. The primary endpoint was progression-free survival and key secondary endpoints included time to second disease progression or death and overall survival.

About ovarian cancer

Worldwide, ovarian cancer is the seventh most common cancer and the eighth leading cause of cancer death in women. The five-year survival rate for ovarian cancer worldwide is 30-40%. In 2012, there were nearly 239,000 new cases diagnosed and around 152,000 deaths. For newly diagnosed advanced ovarian cancer, the primary aim of treatment is to delay progression of the disease for as long as possible and maintain the patient’s quality of life with the intent of achieving complete remission or cure.

About BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

About Lynparza
Lynparza (olaparib) was the first-in-class PARP inhibitor and the first targeted treatment to potentially exploit DNA damage response (DDR) pathway deficiencies, such as BRCA mutations, to preferentially kill cancer cells. Specifically, in vitro studies have shown that Lynparza-induced cytotoxicity may involve inhibition of PARP-enzymatic activity and increased formation of PARP-DNA complexes, resulting in DNA damage and cancer cell death. Lynparza is being tested in a range of DDR-deficient tumour types.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor and AstraZeneca and MSD are working together to deliver it as quickly as possible to more patients across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.