On June 4, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium") reported new data from the ongoing pivotal Phase 3 SIERRA study of Iomab-B’s single agent effect in patients with active, relapsed or refractory AML or Acute Myeloid Leukemia age 55 and above (Press release, Actinium Pharmaceuticals, JUN 4, 2019, View Source [SID1234536852]). The data was presented by SIERRA investigator Benjamin Tomlinson, M.D., Adult Hematologic and Stem Cell Transplant Section, Seidman Cancer Center, University Hospitals Case Medical Center (Cleveland, OH) in a poster presentation at the 2019 ASCO (Free ASCO Whitepaper) or American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting that is being held from May 31st – June 4th at the McCormick Place, Chicago.

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

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

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

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

Sources:

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

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

About Iomab-B

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

About Actinium Pharmaceuticals, Inc.

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on improving patient access and outcomes to cellular therapies such as BMT or Bone Marrow Transplant and CAR-T with its proprietary ARC or Antibody Radiation-Conjugate targeted conditioning technology. Actinium

On June 3, 2019 Nordic Nanovector ASA (OSE: NANO) reported that the European Patent Organisation (EPO) has granted the company’s European Patent covering the use of Betalutin or Humalutin in combination with anti-CD20 antibodies for the treatment of non-Hodgkin’s lymphoma (NHL) (Press release, Nordic Nanovector, JUN 3, 2019, View Source [SID1234553449]). The same patent has also been issued in Japan, China, Australia, Hong Kong, Israel, Russia and Singapore while the patent is pending in USA, Brazil, Canada, Indonesia, India, Korea, Mexico, New Zealand, Philippines, Ukraine and South Africa.

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This patent is a result of Nordic Nanovector’s continued focus on securing intellectual property rights on its pipeline of novel CD37-targeting drug candidates.

Patents covering Betalutin and Humalutin, as well as their medical applications have already been granted in Europe, USA, Canada, China, Hong Kong, Australia, Indonesia, Israel, Japan, Korea, Mexico, New Zealand, Philippines, Russia, Singapore, Ukraine and South Africa. India, Brazil and Thailand are expected to be granted soon.

Finally, two newer patent applications related to Betalutin’s clinical applications and combination with other drugs have also been filed. The latest application has been made public on the 31 May under WO/2019/101789.

On June 3, 2019 Ascentage Pharma, a globally-focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, hepatitis B virus and age-related diseases, reported that the company presented new data of two apoptosis-targeted drug candidates APG-115 (a novel MDM2-p53 inhibitor) and APG-1387 (a novel IAP inhibitor) at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Ascentage Pharma, JUN 3, 2019, View Source [SID1234536846]).

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With the theme "Caring for Every Patient, Learning from Every Patient", 2019 ASCO (Free ASCO Whitepaper) Annual Meeting attracted over 40,000 oncologists and researchers globally to present and share the cutting-edge research and achievements in clinical oncology in Chicago from May 31-June 4.

Ascentage Pharma presented the data from its most recent clinical trials of APG-115 in China and U.S. (Board #118 and #116), and the data of phase I study of APG-1387 as a monotherapy or in combination with pembrolizumab in treatments of patients with advanced solid tumors (Board #117).

It is encouraging that in the study of APG-115 as a monotherapy, a confirmed PR was observed in 1 patient with liposarcoma (TP53-WT and MDM2Amp), with target lesion decreased 64%.

"Liposarcoma is a common histological type of malignant soft tissue sarcomas, accounting for about 15% of soft tissue sarcomas. There is no effective treatment for it and the probability of recurrence is high. Liposarcoma belongs to the ‘cold tumor’ type and has a poor response to immunotherapy," said Pro. Xing Zhang, Chief physician of Melanoma and Sarcoma Medical Oncology Unit of Sun Yat-sen University Cancer Center. She continued, "We believe APG-115 is an efficient MDM2-p53 inhibitor. The data of Phase I study of APG-115 in Chinese patients with liposarcomas is encouraging. We enrolled 14 patients, 8 with liposarcoma; a confirmed PR was observed in one liposarcoma patient after 4 months of treatment discontinuance. Another 5 patients achieved SD (including 2 liposarcoma patients). Based on clinical trial results, APG-115 is well-tolerated and with acceptable safety profile. We expect further data to address the unmet medical needs."

There have also been promising advances in the Phase I study of a novel IAP inhibitor, APG-1387, as a monotherapy in treatments of patients with advanced solid tumors. Drew W. Rasco, M.D., Associate Director of Clinical Research at the START Center for Cancer Care in San Antonio commented: "Among 10 mPC (metastatic pancreatic cancer) patients treated with APG-1387 monotherapy, 3 patients achieved SD. One patient at MTD received SD for >9 cycles (3-wk a cycle) with the best response +6%, still ongoing; one patient achieved SD for > 8 months with best response of -16.7% tumor shrinkage. This preliminary result is worth mentioning, because mPC patients in general have only 3-6 months survival time, and overall survival rate of one year is 8.8%. Currently there is no effective treatment. We look forward to additional data from the on-going studies."

"APG-115 and APG-1387 are two apoptosis targeting products in clinical development of Ascentage Pharma. These results show our further progress in clinical development of targeting apoptosis. We are working hard to provide more therapy options for patients as soon as possible," said Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma.

– A Phase I Study of a Novel MDM2-P53 Antagonist APG-115 in Chinese Patients with Advanced Solid Tumors

Through April 23, 2019, 14 patients with advanced solid tumors (8 LPSs) received APG-115 ranging from 100-200mg, QOD, 3 weeks on 1 week off, in a 4-week cycle.
Two DLTs judged by investigator at 200mg (thrombocytopenia and febrile neutropenia). APG-115 was well-tolerated across all dose levels tested and the MTD was 150mg, due to the late onset thrombocytopenia, safety expansion was ongoing at 100mg. The most common Grade ≥3 AEs were hematologic toxicities, particularly thrombocytopenia, which were predictable as the activation of p53 in the bone marrow.
APG-115 displayed approximately linear pharmacokinetics over 100-200mg range.
A confirmed PR was observed in 1 patient with liposarcoma (TP53-WT and MDM2Amp) at the 150mg, and the duration of response has lasted after 4 months of treatment discontinuance.
– A Phase I study of a Novel MDM2 Antagonist APG-115 in Patients with Advanced Solid Tumors

Through April 19, 2019, total 29 patients were treated with APG-115 at various doses range from 10-300mg.
Most common TRAEs (>10%): fatigue, nausea, vomiting, decreased appetite, diarrhea, neutrophil count decreased, platelet count decreased, white blood cell count decreased.
Platelet count decreased, fatigue, and nausea were determined as DLTs.
APG-115 at 100mg QOD (3 weeks on, 1 week off) was well-tolerated. The MTD/RP2D of APG-115 monotherapy was determined as 100mg.
Base on the preliminary anti-tumor data, APG-115 is active. Nine patients achieved SD among 19 response evaluable patients. 50% (5/10) patients at MTD achieved SD among response evaluable patients.
PK analyses have shown that AUC and Cmax generally increase dose proportionally over the dose range of 20-300mg.
Serum MIC-1 (biomarker of TP53 activation) increase was exposure dependent within the dose range tested in patients with solid tumors.
Further evaluation of APG-115 in combination with pembrolizumab in patients with advanced solid tumors is ongoing.
– A Phase I Study of a Novel IAP Inhibitor APG-1387 as a Monotherapy or in Combination with Pembrolizumab in Treatments of Patients with Advanced Solid Tumors

Through April 19, 2019, 24 patients had been treated with APG-1387 and 5 patients had been treated with APG-1387 plus pembrolizumab.
APG-1387 was well tolerated and had manageable adverse events. Most common TRAEs (>10%) are fatigue.
Two DLTs were observed at 60mg including lipase increase and facial nerve disorder, MTD of APG-1387 monotherapy was determined as 45mg.
Three out of 10 mPC patients in APG-1387 monotherapy (at 45mg) achieved SD, one of them at 45 mg has been treated > 9 cycles with confirmed SD (+6%).
Preliminary PK data of APG-1387 showed a dose proportionality in exposure (Cmax and AUC) over the dose range of 20-45 mg.
APG-1387 treatment induced significant XIAP suppression in PBMCs and cytokine (especially IL-12p40 and IL-10) release in serum, suggesting a potential pharmacodynamics and host immunomodulation effects.
The potential effects of APG-1387 alone or in combination with pembrolizumab deserve further exploration in patients with advanced pancreatic cancer.
About APG-115

APG-115 is an orally administered, selective, small molecule inhibitor of the MDM2-p53 PPI. APG-115 has strong binding affinity to MDM2 and is designed to activate p53 tumor suppression activity by blocking the MDM2-p53 PPI. APG-115 is currently in Phase I clinical trials in China and the United States in patients with ACC (Adenoid cystic carcinoma) and other sarcomas. APG-115 is in Phase Ib/II combination study with pembrolizumab in the U.S.

About APG-1387

APG-1387 is a novel small molecule IAP inhibitor (Inhibitor of Apoptosis Protein). Ascentage Pharma is developing APG-1387 globally, and has completed dose escalation Phase I clinical trials in advanced solid tumors in China and Australia, and a Phase I clinical trial of APG-1387 and pembrolizumab combination is currently ongoing in the U.S. APG-1387 is also being investigated for the treatment of patients with chronic hepatitis B virus in China.

On June 3, 2019 ImmunityBio , a privately held immunotherapy company at late stage clinical development, that aims to synergistically deploy a broad portfolio of biological molecules as an integrated cancer vaccine platform targeting multiple tumor types without the use of high-dose chemotherapy, reported that Dr. Patrick Soon-Shiong will be presenting at the Jefferies 2019 Annual Healthcare Conference being held in New York City from June 4th-7th 2019 (Press release, ImmunityBio, JUN 3, 2019, View Source [SID1234542351]). The presentation and one-on-one discussions will launch the privately held company with a portfolio of over 20 first in class biological molecules deployed to orchestrate the innate and adaptive immune system, and will feature clinical updates of multiple trials with registrational intent.

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Conference Details:

Event: Jefferies 2019 Annual Healthcare Conference

Date/Time: Tuesday, June 4, 2019, Presentation at 8:00am ET

Location: New York, NY

For more information regarding ImmunityBio please visit www.ImmunityBio.com

On June 3, 2019 SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PD-0325901, an investigational, oral, small molecule inhibitor of MEK1 and MEK2, for the treatment of patients ≥ 2 years of age with neurofibromatosis type 1-associated inoperable plexiform neurofibromas that are progressing or causing significant morbidity (Press release, SpringWorks Therapeutics, JUN 3, 2019, View Source [SID1234538850]).

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Neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) is a rare genetic disorder characterized by mutations in the MAPK pathway, leading to the growth of peripheral nerve sheath tumors that cause significant pain, disfigurement and morbidity. NF1-PNs are most often diagnosed in the first two decades of life and are characterized by aggressive tumor growth, which is typically more rapid during childhood.1-3 There are currently no therapies approved for the treatment of NF1-PN.

"The Fast Track designation recognizes that plexiform neurofibromas have a substantial impact on the lives of patients, and that our MEK inhibitor has the potential to address the significant needs faced by this patient community who currently do not have an FDAapproved treatment," said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. "We look forward to continuing to work closely with the FDA on our upcoming Phase 2b study, which will enroll pediatric and adult NF1 patients with plexiform neurofibromas.

" The FDA’s Fast Track program is designed to expedite the development and review of drugs with the potential to treat serious or life-threatening conditions, and with nonclinical or clinical data that demonstrate the potential to address unmet medical needs. Fast Track designation enables a company to have frequent communication with the FDA throughout the drug development and review process.4

In November 2018, the FDA granted Orphan Drug designation for PD-0325901 for the treatment of neurofibromatosis type 1. SpringWorks expects to initiate a Phase 2b singlearm, open-label study of PD-0325901 in pediatric and adult patients with NF1-PN in the third quarter of 2019.

About Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is a rare genetic disorder that is caused by mutations in the NF1 gene, and that affects both children and adults. Throughout their lifetime, about 30 to 50 percent of NF1 patients progress to a more severe form of the disease that results in the development of plexiform neurofibromas (PN), which are progressive peripheral nerve sheath tumors that cause severe pain, disfigurement, debilitating loss of range of motion, and can significantly shorten lifespan.1-3 The clinical course of NF1-PN is heterogeneous with varying manifestations and severity across patients.

It is estimated that NF1 affects 1 in 3,000 individuals worldwide, and that there are approximately 100,000 patients in the United States living with this disease.5 Most patients with NF1-PN are treated with surgical removal of the tumors, sometimes requiring amputation; however, surgery has variable success rates and a high rate of recurrence has been observed because of the aggressive nature of these tumors.6 There are no therapies currently approved for the treatment of NF1-PN.

About PD-0325901

PD-0325901 is an oral small molecule inhibitor of MEK1 and MEK2. MEK proteins occupy a pivotal position in the MAPK pathway, a key signaling network that regulates cell growth and survival, and whose activity is highly relevant in multiple oncology and rare disease indications.

PD-0325901 has been evaluated in several Phase 1 and Phase 2 clinical trials, with over 200 subjects having been exposed to treatment. A Phase 2 trial conducted by the Neurofibromatosis Clinical Trial Consortium evaluated PD-0325901 in 19 adolescent and adult patients with inoperable and symptomatic or growing plexiform neurofibromas. Results demonstrated an objective response in 42 percent of patients, prospectively defined as having greater than or equal to 20 percent reduction in tumor volume as measured by volumetric MRI. In the clinical trial, PD-0325901 given at 2mg/m2 on a 3-week on 1-week off schedule was generally well-tolerated. The most commonly reported treatmentemergent grade 2 or higher AEs were acneiform rash in 53% (10/19), fatigue in 26% (5/19) and nausea in 21% (4/19) of patients.

SpringWorks is evaluating PD-0325901 as a monotherapy for the treatment of patients with NF1-PN and is also pursuing PD-0325901 in combination with other rational anti-cancer agents across a range of solid tumors.