Puma Biotechnology Announces Results of CHMP Reexamination of MAA for Neratinib for Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer

On June 26, 2018 Puma Biotechnology, Inc. (Nasdaq: PBYI) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive trend vote recommending the approval of the Marketing Authorisation Application (MAA) for neratinib for the extended adjuvant treatment of early stage HER2-positive hormone receptor positive breast cancer (Press release, Puma Biotechnology, JUN 26, 2018, View Source [SID1234527476]). Today’s decision follows a reexamination of the negative opinion announced by the CHMP at its formal meeting with the Company to discuss the MAA on February 23, 2018. The CHMP communicated its intention to hold a final vote at its next meeting.

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About HER2-Positive Breast Cancer

Approximately 20% to 25% of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

Merrimack Announces Top-Line Results from Randomized Phase 2 Trial of MM-141 in Front-Line Metastatic Pancreatic Cancer

On June 26, 2018 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK), a clinical-stage oncology company focused on biomarker-defined cancers, reported top-line results from the CARRIE study, a randomized Phase 2 trial evaluating the addition of MM-141 (istiratumab) to standard-of-care treatment in patients with previously untreated metastatic pancreatic cancer and high serum levels of free Insulin-like Growth Factor-1 (IGF-1) (Press release, Merrimack, JUN 26, 2018, View Source [SID1234527475]). The study did not meet its primary or secondary efficacy endpoints in patients who received MM-141 in combination with nab-paclitaxel and gemcitabine, compared to nab-paclitaxel and gemcitabine alone. These results were consistent in all subgroups analyzed. Based on these results, Merrimack will not devote additional resources to the development of MM-141.

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Merrimack plans to present the complete data from this Phase 2 study at an upcoming medical oncology meeting.

"Pancreatic cancer is the third leading cause of cancer-related death in the Unites States and a very difficult cancer to treat," said Sergio Santillana, M.D., MSc., Chief Medical Officer of Merrimack. "Although we were unsuccessful in our effort to improve the standard of care for these patients, we want to express our gratitude to our investigators and our team, and, of course, to the patients and their families for their support and participation in the CARRIE study."

"While these results are disappointing, looking forward our focus remains on the continued development of our deep, wholly-owned pipeline, including two clinical programs, MM-121 and MM-310, with data readouts expected in 2018," said Richard Peters, M.D., Ph.D., President and CEO of Merrimack.

MM-121 (seribantumab), a monoclonal antibody targeting the HER3 (ErbB3) receptor, is being tested in combination with standard-of-care treatment in two randomized Phase 2 studies: SHERLOC, in patients with non-small cell lung cancer, and SHERBOC in patients with metastatic breast cancer. Both studies are enrolling patients with high tumor expression of heregulin, the signal for the HER3 receptor. Top-line results from the SHERLOC study are expected in 2H 2018.

MM-310, an antibody-directed nanotherapeutic targeting the EphA2 receptor, is currently being tested in a Phase 1 study in solid tumors, with safety data and the maximum tolerated dose expected in 2H 2018.

Arcus Biosciences and Infinity Pharmaceuticals Announce Clinical Collaboration to Evaluate Lead Programs in Triple-Combination Studies

On June 26, 2018 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage biopharmaceutical company focused on creating innovative cancer immunotherapies, and Infinity Pharmaceuticals, Inc. (NASDAQ:INFI), a clinical-stage biopharmaceutical company developing IPI-549, a first-in-class immuno-oncology product candidate that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), reported that they have entered into a clinical collaboration to evaluate two triple combination therapies in selected tumor types which typically show minimal response to checkpoint inhibition monotherapy (Press release, Arcus Biosciences, JUN 26, 2018, View Source [SID1234527474]).

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The collaboration will evaluate IPI-549 in combination with AB928, Arcus’s dual adenosine receptor antagonist, and AB122, Arcus’s anti-PD-1 antibody, as well as IPI-549 in combination with AB928 and chemotherapy in patients with triple negative breast cancer (TNBC) or ovarian cancer in four separate cohorts. These four cohorts will be incorporated into Arcus’s recently initiated Phase 1/1b trial to evaluate AB928 combinations in TNBC and ovarian cancer. As both macrophages and high adenosine levels are believed to play critical roles in creating a highly immune-suppressive tumor microenvironment in TNBC and ovarian cancer, the triple combinations being evaluated could represent a promising approach to treating these tumor types. By intervening in multiple mechanisms that mediate immuno-suppression, the companies hope to address two tumor types that lack effective therapies, particularly in later lines of treatment.

"This partnership with Infinity is important as, for the first time, we will be investigating the potential for the triple combination of a selective PI3K-gamma inhibitor, a dual adenosine receptor antagonist, and either a PD-1 inhibitor or chemotherapy to effectively treat patients with triple negative breast cancer or ovarian cancer," said Terry Rosen, Ph.D., Chief Executive Officer of Arcus Biosciences. "This collaboration also allows us to expand the number of promising combinations with strong biological rationale that we plan to evaluate in our recently initiated Phase 1/1b trial for AB928. Arcus has carefully considered which immuno-oncology therapies can best target immune suppressive macrophages and has concluded that selective inhibition of PI3K-gamma is a fundamental mechanism for reprogramming macrophages from a pro-tumor to an anti-tumor function."

"This collaboration with Arcus Biosciences enables an important expansion of our clinical development of IPI-549, investigating IPI-549 in triple-combination therapy with other important immuno-oncology agents as well as with chemotherapy," said Adelene Perkins, Chief Executive Officer and Chair of Infinity Pharmaceuticals. "Combining these agents may result in enhanced reduction of pro-tumor immune suppression and increased anti-tumor immune activation. We look forward to working with the terrific team at Arcus in investigating these triple-combination therapies as potentially new treatment options for patients with cancers that are not adequately addressed by existing therapies."

Under the terms of the agreement, Infinity and Arcus will share equally expenses related to the four triple-combination cohorts to evaluate the safety and activity of IPI-549 + AB928 + AB122 and IPI-549 + AB928 + chemotherapy. Each of the four triple-combination cohorts will enroll approximately 15 patients. Topline data from these studies are expected in 2019.

About AB928

AB928 is an orally bioavailable, highly potent antagonist of the adenosine 2a and 2b receptors. The activation of these receptors by adenosine interferes with the activity of key populations of immune cells and inhibits an optimal anti-tumor immune response. By blocking these receptors, AB928 has the potential to reverse adenosine-induced immune suppression within the tumor microenvironment. AB928 was designed specifically for the oncology setting, with a profile that includes potent activity in the presence of high concentrations of adenosine and a minimal shift in potency due to non-specific protein binding, both essential properties to be efficacious in the tumor microenvironment. AB928 has other attractive features, including high penetration of tumor tissue and low penetration through the healthy blood-brain barrier. In a Phase 1 trial in healthy volunteers, AB928 has been shown to be safe and well tolerated and to have pharmacokinetic and pharmacodynamic profiles consistent with a once-daily dosing regimen.

About IPI-549 and the Ongoing Phase 1/1b Study

IPI-549 is an investigational first-in-class, oral, immuno-oncology product candidate targeting tumor-associated myeloid cells through selective phosphoinositide-3-kinase-gamma (PI3K-gamma) inhibition, thereby reducing pro-tumor macrophage function and increasing anti-tumor macrophage function. In preclinical studies, IPI-549 demonstrated the ability to reprogram macrophages from a pro-tumor (M2), immune-suppressive function, to an anti-tumor (M1) immune-activating function and enhance the activity of, and overcome resistance to, checkpoint inhibitors.i ii As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially additive or synergistic approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

The ongoing Phase 1/1b study being conducted by Infinity is designed to evaluate the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy and in combination with Opdivo in approximately 200 patients with advanced solid tumors.iii The study includes monotherapy and combination dose-escalation components, in addition to monotherapy expansion and combination expansion components. The monotherapy dose-escalation and expansion components are complete. The combination dose-escalation component is also complete, and combination expansion cohorts are enrolling.

The combination expansion component of the study includes multiple cohorts designed to evaluate IPI-549 in patients with specific types of cancer, including patients with non-small cell lung cancer (NSCLC), melanoma and head and neck cancer whose tumors show initial resistance or initially respond to but subsequently develop resistance to immune checkpoint blockade therapy. The combination expansion component also includes a cohort of patients with triple negative breast cancer (TNBC) who have not been previously treated with immune checkpoint blockade therapy, a cohort of patients with mesothelioma, a cohort of patients with adrenocortical carcinoma and a cohort of patients with high baseline blood levels of MDSCs.

Actinium Pharmaceuticals Announces Dosing of 38th Patient and 25 Percent Enrollment in Iomab-B Pivotal SIERRA Trial

On June 26, 2018 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN:ATNM) ("Actinium" or "the Company"), reported that it has dosed the 38th patient in the pivotal Phase 3 SIERRA (Study of Iomab-B in Elderly Relapse Refractory Acute Myeloid Leukemia) study of Iomab-B, reaching twenty-five percent of patient enrollment (Press release, Actinium Pharmaceuticals, JUN 26, 2018, View Source [SID1234527473]). As a result, the trial’s independent Data Monitoring Committee (DMC) will review the trial data at its next meeting, which has been scheduled for August. The SIERRA trial is a 150 patient, randomized, and controlled multi-center trial that is currently open at 16 leading transplant centers in the US.

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The Company highlighted the recent initiatives taken to strengthen the outlook for the trial. Based on the higher than anticipated crossover rate previously announced after the first DMC meeting, the Company deemed it appropriate to increase the number of additional treatment options acceptable for utilization in the control arm. This was done to accommodate requests from the principal investigators at various sites. The amended protocol now allows additional treatment options in the control arm including Mylotarg, Venetoclax, and the FLT3 inhibitors Midostaurin and Sorafenib. Importantly, the Company notes that these treatments may be used based on the preference and discretion of the treating physician in keeping with the design of the study’s control arm and are not approved treatments for this patient population. The recent protocol changes have been implemented following review by the FDA and IRB approvals. The Company has also made valuable additions to its clinical organization, including the hiring of Vijay Reddy, M.D., Ph.D., a bone marrow transplant physician with stellar drug development, scientific and clinical experience, as Vice-President of Clinical Development to lead the SIERRA trial. The Company also materially strengthened its clinical operations group with the addition of two directors, two clinical trial associates and a clinical education and support specialist nurse. These initiatives taken since the first DMC update have enabled the recent milestone and are expected to ensure the continued strong progress of the SIERRA trial including both site expansion and enrollment.

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "We are excited to have reached this important milestone for the SIERRA trial. Patients with active relapsed or refractory AML, particularly older patients, have limited treatment options, poor survival prognoses and few successfully receive a bone marrow transplant. We believe Iomab-B has the potential to significantly improve outcomes for these patients and we are optimistic that the SIERRA trial will support approval in an indication with significant unmet needs. We are encouraged that our efforts to expand the choice of regimens in the control arm, the expanded Iomab-B team, and increased communication with trial sites has resulted in the acceleration in enrollment that we expected. With this important milestone behind us, our team is highly motivated to complete enrollment as efficiently as possible and looks forward to the completion of this consequential trial."

Following successful enrollment of twenty-five percent of patients in the SIERRA trial, the Company expects to activate additional clinical trial sites in the United States and Canada with a continued emphasis on leading high-volume BMT centers. In addition, Actinium intends to open clinical trial sites in Europe where Iomab-B has been granted Orphan designation by the European Medicines Agency (EMA) and received Scientific Advice establishing a clear pathway to submit for EU marketing authorization upon successful completion of the SIERRA trial. Based on current forecasts, Actinium expects to complete patient enrollment in 2019. In anticipation of trial completion, Actinium is taking necessary steps to prepare for a Biologics License Application (BLA) submission and is undertaking pre-commercialization activities that are being led by Chief Commercial Officer, Anil Kapur. The SIERRA trial will have multiple data readouts including scheduled DMC safety analyses after twenty-five, fifty and seventy-five percent of patients have been enrolled. In addition, Actinium, at its discretion, may request efficacy analyses by the DMC after 70 and 110 patients have reached the primary endpoint of durable complete remission (dCR) of at least 180 days.

Sandesh Seth, Actinium’s Chairman and CEO said, "Actinium is committed to be the leader in the development and commercialization of targeted conditioning agents that improve bone marrow transplant access and outcomes. Through our development of Iomab-B, we have built strong relationships with leading BMT sites and investigators, gained invaluable insights into the BMT field, and have a deep appreciation for the needs of BMT patients. In addition, Actinium has built the exoskeleton of a commercial supply chain that regularly supplies our drug candidates to the major BMT sites. This progress is inspiring to our entire team and is enabling us to create and develop the only multi-target, multi-disease clinical pipeline of targeted conditioning agents for bone marrow transplant. This recent milestone marks what I anticipate will be a series of value creating clinical advancements across our entire pipeline as we build the leading portfolio of targeted conditioning treatments."

About Iomab-B

Iomab-B is a targeted conditioning therapy given in conjunction with a bone marrow transplant (BMT) and is comprised of the CD45 targeting monoclonal antibody BC8 labeled with the radioisotope Iodine-131. The high dose chemotherapy used in BMT conditioning has significant toxicities and, as a result, many patients, particularly many older patients, do not receive a BMT. Iomab-B is intended to improve BMT access and outcomes by eliminating the use of intense chemotherapy in BMT conditioning. Actinium obtained the worldwide exclusive license to BC8 from the Fred Hutchinson Cancer Research Center. BC8 has been studied in several hundred patients across multiple Phase 1 and Phase 2 trials for patients with hematologic malignancies including AML, myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (ALL), Hodgkin’s and Non-Hodgkin’s lymphoma and multiple myeloma.

About the SIERRA Trial

The Study of Iomab-B in Elderly Relapse Refractory Acute Myeloid Leukemia (SIERRA) trial is studying Iomab-B prior to a bone marrow transplant (BMT) in patients age 55 and above with acute myeloid leukemia (AML) who have active relapsed or refractory disease. It is a 150-patient controlled trial, randomized 1:1 that will compare Iomab-B followed by a BMT to physician’s choice of salvage chemotherapy with the primary endpoint being durable complete remission (dCR) rate of at least 180 days and the secondary endpoint being Overall Survival (OS) at one year. Patients in the control arm that receive salvage chemotherapy may cross over to Iomab-B treatment and BMT if they do not attain a CR with the salvage therapy. When they do so, they are counted as failures for the primary endpoint, which is durable complete remission for at least 180 days. The U.S. Food and Drug Administration (FDA) has agreed that the SIERRA trial is a pivotal study.

AbbVie and Calico Announce Extension of Groundbreaking Collaboration

On June 26, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, and Calico, a company focused on aging research and therapeutics, reported an extension of their collaboration to discover, develop and bring to market new therapies for patients with age-related diseases, including neurodegeneration and cancer (Press release, AbbVie, JUN 26, 2018, View Source [SID1234527472]).

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Calico is the Alphabet-backed life sciences company that is led by former Genentech chairman and CEO Arthur D. Levinson, Ph.D. With more than 150 employees, Calico has established a world-class research and development facility in the San Francisco Bay Area.

Working together with AbbVie, Calico pursues discovery-stage research and development. AbbVie provides scientific and clinical development support and will lend its commercial expertise to lead future development and commercialization activities. Since 2014, the collaboration between the two companies has produced more than two dozen early-stage programs addressing disease states across oncology and neuroscience and yielded new insights into the biology of aging.

"We’ve built a successful collaboration – both scientifically and culturally – that is advancing cutting-edge science," said Michael Severino, M.D., executive vice president, research and development, chief scientific officer, AbbVie. "Calico has attracted an outstanding team of world-class scientists and the extension of this collaboration allows us to further build on the research we’ve done to identify transformative treatment options for patients with age-related diseases."

"Our collaboration with AbbVie has fully met our high expectations," said Dr. Levinson. "Our initial agreement created a unique partnership and this extension will accelerate further our efforts to understand the science of aging to advance novel therapies for patients."

Under the terms of the agreement, the collaboration between the two companies is now extended for an additional three years. Calico will be responsible for research and early development until 2022 and will advance collaboration projects through Phase 2a through 2027. AbbVie will continue to support Calico in its early R&D efforts and, following completion of Phase 2a studies, will have the option to manage late-stage development and commercial activities. Both parties will share costs and profits equally. AbbVie and Calico will each commit to contribute an additional $500 million to the collaboration.