On January 29, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that it has enrolled the first patient in the diffuse large B-cell lymphoma (DLBCL) cohort of its Phase 2 clinical trial of CLR 131, its lead radiotherapeutic Phospholipid Drug ConjugateTM (PDCTM) (Press release, Cellectar Biosciences, JAN 29, 2018, View Source [SID1234523611]). This group represents the fourth and final cohort of the company’s Phase 2 study for patients with relapsed or refractory B-cell hematologic cancers. The Company expects to enroll up to 10 patients with DLBCL into this cohort prior to conducting an interim analysis. If these interim data are positive, the DLBCL cohort could be expanded by an additional 10-20 patients.

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"DLBCL is a rare hematologic cancer with few treatment options and the expansion of the Phase 2 trial provides the opportunity to further explore the broad treatment potential of CLR 131 in an area of significant unmet need. We are now exploring CLR 131 in six hematologic malignancies and we expect to initiate Phase 1 studies in head & neck cancer and pediatric tumors in 2018," stated James Caruso, president and chief executive officer of Cellectar Biosciences. "Importantly, we are able to undertake our development plans with modest shareholder investment as our Phase 2 study is partially funded through a National Cancer Institute (NCI) Small Business Innovation Research grant. In addition, the Phase 1 head & neck study will be predominantly funded through a NCI Specialized Programs of Research Excellence grant and costs for the pediatric study will be shared with our partners at the University of Wisconsin."

About the Phase 2 Study of CLR 131

We are conducting the Phase 2 study for patients with relapsed or refractory B-cell hematologic cancers in approximately 10 leading cancer centers in the United States. These hematologic cancers include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and DLBCL.

The study’s primary endpoint is clinical benefit response (CBR), with additional secondary endpoints of progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a single 25.0 mCi/m2 dose of CLR 131, with the option for a second 25.0 mCi/m2 dose approximately 75-180 days later.

In addition to the CLR 131 infusion(s), MM patients will receive 40 mg oral dexamethasone weekly for up to 12 weeks. Efficacy responses will be determined in accordance with the latest International Multiple Myeloma Working Group criteria. Efficacy for all lymphoma patients will be determined according to Lugano criteria. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About Diffuse Large B-Cell Lymphoma

According to the Lymphoma Research Foundation, diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin’s lymphoma (NHL), accounting for about 30 percent of newly diagnosed cases of NHL in the United States.

The American Cancer Society’s most recent estimates for NHL for 2018 project approximately 74,680 people (41,730 males and 32,950 females) will be diagnosed with NHL including both adults and children. They estimate that approximately 19,910 people will die from this cancer (11,510 males and 8,400 females).

DLBCL occurs in both men and women, although it is slightly more common in men. Although DLBCL can occur in childhood, its incidence generally increases with age, and roughly half of patients are over the age of 60.

DLBCL is an aggressive (fast-growing) lymphoma that can arise in lymph nodes or outside of the lymphatic system, in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain. Often, the first sign of DLBCL is a painless, rapid swelling in the neck, underarms, or groin that is caused by enlarged lymph nodes. For some patients, the swelling may be painful. Other symptoms may include night sweats, fever, and unexplained weight loss. Patients may notice fatigue, loss of appetite, shortness of breath, or pain.

About CLR 131

CLR 131 is an investigational compound under development for a range of orphan designated cancers. It is currently being evaluated as a single-dose treatment in a Phase I clinical trial in patients with relapse or refractory (R/R) MM as well as in a Phase II clinical trial for R/R MM and select R/R lymphomas with either a one- or two-dose treatment. Based upon preclinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating solid and hematological tumors and may provide patients with therapeutic benefits, including overall survival, an improvement in progression-free survival, surrogate efficacy marker response rate, and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131, directly to tumor cells. The FDA has granted orphan drug designation for CLR 131 in the treatment of MM.

About Phospholipid Drug ConjugatesTM (PDCsTM)

Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The PDC platform provides selective delivery of a diverse range of oncologic payloads to cancerous cells, whether a hematologic cancer or solid tumor, the primary tumor, a metastatic tumor or cancer stem cells. The selective delivery of oncologic payloads allows for the modification of the payloads’ therapeutic window which may maintain or enhance drug potency while reducing the number and severity of adverse events. The PDC platform takes advantage of a metabolic pathway utilized by all tumor cell types in all stages of the tumor "cycle." This property allows the PDC molecules to gain access to the intracellular compartment of the tumor cells and for the PDCs to continue to accumulate over time, which enhances drug efficacy. The PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens as are required by other targeted delivery platforms. In addition to the benefits provided by the mechanism of entry, PDCs offer the potential advantage of having the ability to be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered via the PDC. The PDC platform possesses the potential for the discovery and development of the next generation of cancer-targeting agents.

On January 29, 2018 Diffusion Pharmaceuticals Inc. (NASDAQ:DFFN) ("Diffusion" or "the Company"), a clinical-stage biotechnology company focused on extending the life expectancy of cancer patients, reported that the first patient has been dosed in the Company’s Phase 3 clinical trial with trans sodium crocetinate ("TSC") in patients with newly-diagnosed inoperable glioblastoma multiforme ("GBM"), a type of brain cancer (Press release, Diffusion Pharmaceuticals, JAN 29, 2018, View Source [SID1234523612]). The INTACT (INvestigating Tsc Against Cancerous Tumors) trial will compare standard of care ("SOC") radiation therapy ("RT") and chemotherapy plus TSC against SOC alone.

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"We are pleased to be dosing patients so soon following the opening of the INTACT trial just a few weeks ago," said David Kalergis, Chief Executive Officer of Diffusion Pharmaceuticals. "We believe that this Phase 3 study will offer new hope for inoperable GBM patients who are administered TSC along with their standard therapies."

The INTACT Phase 3 study follows a previous Phase 2 GBM study in which the inoperable patient subgroup showed a nearly four-fold increase in survival compared with historical controls when TSC was added to their treatment regimen (40.0% alive at two years vs. 10.4%). TSC’s unique mechanism of action affects the tumor micro-environment, making treatment-resistant cancer cells more susceptible to the tumor-killing power of conventional RT and chemotherapy (temozolomide) by re-oxygenating the hypoxic portion of the tumor. The Company believes that a largely intact GBM tumor vasculature with limited surgical resection is conducive to TSC’s tumor re-oxygenation properties, and that this contributed to the survival increase in the Phase 2 GBM inoperable patient subgroup.

The trial will screen 300 patients and enroll 264 with the expectation that results from 236 patients will be available for analysis. Enrolled patients will be randomized in a 1:1 ratio into treatment and control groups. Patients in the treatment group will receive SOC temozolomide and RT plus an intravenous bolus of TSC administered shortly before their SOC treatments. Patients in the control group will receive SOC alone. The study will compare overall survival at two years between patients in the two groups. Up to 100 clinical sites in the U.S. and Europe are expected to participate.

About the GBM Phase 3 INTACT Trial

The INTACT clinical trial is an open-label, randomized, controlled, Phase 3 safety and efficacy registration trial. Subjects will be randomized at baseline to SOC for first-line treatment of GBM plus TSC, or to SOC alone. The SOC for GBM is temozolomide plus RT for 6 weeks followed by 28 days of rest, followed by 6 cycles of post-radiation temozolomide treatment.

For patients randomized to the TSC group, TSC will be administered during both the RT and post-radiation temozolomide treatment periods.

During the RT treatment period subjects will receive:

Focal RT delivered as 60Gy/30 fractions scheduled at 2Gy/day for 5 days each week (Monday through Friday) for 6 weeks.
Temozolomide 75 mg/m2 orally once daily (usually administered the night preceding each RT session) starting the evening before the first RT session over a period of 42 calendar days with a maximum of 49 days.
TSC 0.25 mg/kg IV for 3 days each week (e.g., Monday, Wednesday, Friday, or other schedule that supplies a minimum 3 TSC doses per week) administered between 45 to 60 minutes prior to each RT session.
During the 28-day rest period all subjects will receive no treatment.

During the post-radiation 6-cycle temozolomide treatment period:

All subjects will receive 28-day oral temozolomide (150 mg/m2 first cycle and 200 mg/m2 all subsequent cycles as tolerated) administered on Day 1-5 (Monday through Friday) of each 28-day cycle.
Controls will receive oral temozolomide at night at home per the SOC and are not required to attend clinic visits during this period.
Subjects randomized to TSC will receive TSC 1.5 mg/kg (or another dose if recommended by the Data Safety Monitoring Board ("DSMB") 1.5 to 2 hours before their temozolomide dose during the daytime for 3 days during the first week of each 28-day cycle (Days 1, 3, and 5; e.g., Monday, Wednesday, Friday or other schedule that supplies at minimum 3 TSC doses per week). The Tuesday, Thursday doses will be given at night at home. Long-acting antiemetics may be administered prior to daytime temozolomide dosing on Days 1, 3, 5.
The safety, tolerability and pharmacokinetics ("PK") of TSC at higher doses than 0.25 mg/kg with temozolomide will be assessed during adjuvant therapy. TSC at doses between 0.25 mg/kg and up to 1.5 mg/kg in combination with concomitant temozolomide will be assigned (not randomized) in the first 8 subjects enrolled in the INTACT trial. These patients will undergo RT plus temozolomide plus TSC treatment (0.25 mg/kg) for 6 weekly cycles followed by 4 weeks of rest in standard fashion. At the Week 10 clinic visit the same 8 subjects will be assigned to treatment, with 2 subjects each assigned to TSC at doses of 0.25, 0.50, 1.0, and 1.5 mg/kg. These subjects will be studied in parallel for 2 28-day cycles with inclusion of appropriate blood sampling collection for TSC and temozolomide PK. The DSMB will examine the resultant safety data after 2 cycles (Weeks 11 through 18 of post-radiation temozolomide treatment period; Days 1 to 56). The DSMB may recommend continued use of the 1.5 mg/kg TSC dose for the post-radiation temozolomide treatment period, or may prescribe another dose based on their observations. Subjects then entering into the INTACT trial will be randomized at baseline between TSC plus SOC, or SOC alone.

Further details about the trial protocol are available at www.clinicaltrials.gov.

The baseline assessment for determining progression-free survival overall response rate and to rule out pseudo-progression will be at 10 weeks via MRI using the modified Response Assessment in Neuro-Oncology scale. The hazard ratio for the trial will be 0.67, which corresponds to 22% two-year survival in the TSC arm, the lower limit of the 95% confidence interval for the biopsy-only subjects in Diffusion’s Phase 2 trial, and 10% survival in the SOC arm. The estimated median survival is therefore 10 months for the SOC arm vs. 14.9 months for the TSC plus SOC arm. In order to achieve 80% power, the trial requires 118 subjects in each arm.

The study will achieve the designed 80% statistical power at 198 events, where an event is defined as death. The first analysis will occur at the earlier of two years follow-up for all subjects or 198 events. If the first analysis is at 198 events, the analysis will be a standard 2-sided stratified log-rank test at the 훼=0.05 significance level. If the first analysis is at two years, the Company will perform the analysis using the O’Brien-Fleming Method.

About Treatment-Resistant Cancers and TSC

Oxygen deprivation at the cellular level (hypoxia) is the result of rapid tumor growth, causing the tumor to outgrow its blood supply. Cancerous tumor cells thrive with hypoxia and the resultant changes in the tumor microenvironment cause the tumor to become resistant to RT and chemotherapy. Using a novel, proprietary mechanism of action, Diffusion’s lead drug TSC appears to counteract tumor hypoxia – and therefore treatment resistance – by safely re-oxygenating tumor tissue, thus enhancing tumor kill and potentially prolonging patient life expectancy. Oxygen levels of normal tissue appear to remain unaffected upon administration of TSC.

On January 29, 2018 Sumitomo Dainippon Pharma presented Presentation Material (Third Quarter Financial Results for FY2017) (Press release, Dainippon Sumitomo Pharma, JAN 29, 2018, View Source [SID1234523623]).

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On January 29, 2018 Lee’s Pharm and Sorrento Therapeutics reported that the Chinese authorities have approved China Oncology Focus Limited (COF, an affiliate of Lee’s Pharmaceutical Holdings Limited, Hong Kong Stock Symbol: 0950.HK) to proceed with the clinical trials for ZKAB001, an anti-PD-L1 monoclonal antibody exclusively licensed to COF for Greater China territories, by Sorrento Therapeutics (Press release, Sorrento Therapeutics, JAN 29, 2018, View Source [SID1234532254]).

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The investigation sites will be:

Beijing Cancer Hospital
The Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Wuhan Union Hospital
Shanghai Sixth People’s Hospital
The trials will be anticipated to use a 3+3 design with 5mg/kg, 10mg/kg and 15mg/kg dosing regimens. Once the Maximum Tolerated Dose (MTD) has been established, additional patients are expected to be recruited in an expanded Phase 1 protocol. Clinical data from these studies could be available by the end of the year 2019, and positive results could lead to conditional approval of the antibody prior to a confirmatory Phase 3 study.

"We are proud to announce the acceptance of the IND for our anti-PD-L1 antibody ZKAB001. It’s further evidence for COF continued commitment to addressing high unmet oncology needs by bringing new effective immuno-oncology therapies to the Chinese market. Throughout the IND-enabling activities and the extensive IND review process by the Chinese FDA, the COF team has worked closely and efficiently with Sorrento colleagues. In the landscape of anti-PD-L1 therapies in China, we believe our program is part of the first wave of immune checkpoint inhibitors. Encouraged by our impressive preclinical data, we are excited about evaluating our immunotherapy and addressing unmet medical needs of cancer patients in the Greater China region. Based on this highly productive first joint project, we look forward to potentially expanding our partnership with Sorrento," said Dr. Xiaoyi (Benjamin) Li, Chief Executive Officer and Executive Director of COF.

"We believe COF’s progress in the development of cancer therapeutics for the Greater China market utilizing our G-MAB library of fully human antibodies is a testimony of the value of Sorrento’s comprehensive portfolio of immuno-oncology platform technologies and products acquired and developed over the years," stated Dr. Henry Ji, Chairman and CEO. "Although our own internal resources are currently focused on the development of CAR-T platforms and programs, we think we have shown success in collaborations and out-licensing of other therapeutic assets to a number of strategic partners. COF’s success in developing ZKAB001 could lead to milestone and royalty payments to Sorrento."

About ZKAB001 (anti-PD-L1 monoclonal antibody)

ZKAB001 is a fully human anti-PD-L1 monoclonal antibody (mAb), an immune checkpoint inhibitor. The mAb blocks the interaction of PD-L1 protein with its receptor PD-1, then suppressing the inhibition of PD-1/PDL1 signal to T cells and enhancing the killing effect of T cells on tumors. This antibody also kills cancer cells through traditional antibody-dependent cell-mediated cytotoxicity (ADCC) recruiting Natural Killer (NK) cells and other effector cells against the tumor potentially further strengthening the anti-tumor effect of the antibody. It was licensed from Sorrento Therapeutics, Inc. (SRNE) to COF in Q4 2014.

On January 29, 2018 Agilent Technologies Inc. (NYSE: A) reported that it has formed a strategic scientific collaboration with the University of Southern California (USC) Michelson Center for Convergent Bioscience to create an Agilent Center of Excellence (COE) in Biomolecular Characterization (Press release, Agilent, JAN 29, 2018, http://www.agilent.com/about/newsroom/presrel/2018/29jan-ca17038.html [SID1234523609]).

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The center will be housed in Michelson Hall, which opened at the university in October 2017 and is a state-of-the-art research facility aimed at establishing a convergence of researchers across science and engineering to work together on multidisciplinary approaches for the development of improved health care through new drugs, diagnostics, and medical devices. The Agilent COE will be a resource for undergraduate and graduate students as well as customers in the area, providing access to new Agilent instrumentation and broad exposure to researchers who are leaders in their respective fields.

"Agilent’s collaboration with the Michelson Center is an excellent example of how academia and industry can work together, sharing knowledge and expertise to shorten the timeline between scientific discoveries and real-world applications," said Darlene Solomon, senior vice president and chief technology officer for Agilent. "Convergent bioscience research requires successful collaboration across multiple disciplines — a holistic approach that is central to Agilent’s view of the future."

Key to the Agilent COE will be collaboration with renowned USC Michelson Center for Convergent Bioscience principal investigator Dr. Valery Fokin. Research at the Fokin lab at USC focuses on chemical reactivity and biological interactions at the molecular level. The lab will contribute to multiple collaborative drug discovery projects ranging from chemical synthesis of screening and focused libraries and biological assay implementation to the development of targeted drug delivery systems, diagnostics, and vaccines.

"As convergent bioscience becomes a major contributor to scientific knowledge and ultimately improved human health, academic and industry collaboration will play a key role," said Stephen Bradforth, divisional dean for natural sciences and mathematics at the USC Dornsife College of Letters, Arts and Sciences. "I’m pleased that Agilent has the vision to support our efforts in this important emerging research field."

Additional notable contributors to this collaboration include Dr. Richard Roberts, chair of the Mork Family Department of Chemical Engineering and Materials Science and professor of chemistry, chemical engineering, and biomedical engineering, and Dr. Steve Kay, who is Provost Professor of Neurology, Biomedical Engineering and Biological Sciences. Dr. Roberts, who is co-director of the Agilent COE with Dr. Fokin, is a renowned expert in the chemical biology of protein synthesis whose breakthrough methods allow researchers to screen 10 trillion independent peptide or protein sequences to understand their functions. Dr. Kay’s research into high-throughput genomics and chemical biology has been integral to the understanding of circadian rhythms, and he is recognized as one of the world’s top experts in this area. Other contributors are Dr. Raymond C. Stevens, Provost Professor of Biological Sciences and Chemistry, and Dr. Peter Kuhn, Dean’s Professor of Biological Sciences. Dr. Stevens and Dr. Kuhn are among the world’s most influential biomedical scientists; their research on structural biology and cancer metastasis have led to important advances in medical treatments and pharmaceutical drugs.