On December 20, 2016 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD), reported that it has received approval from the Competent Authority and Ethics Committee in the UK for its Phase IIb, AIPAC clinical trial of IMP321 (Filing, 6-K, Prima Biomed, DEC 20, 2016, View Source [SID1234517148]). Following conclusion of the safety run in phase, expected in late December, and subject to the dose escalation committee meeting, screening for the larger, randomised phase of the trial is expected to commence in January 2017.
AIPAC (Active Immunotherapy PAClitaxel) is a multi-national, randomised, double-blind, placebo-controlled study of IMP321-plus-paclitaxel in metastatic breast cancer. The safety run-in phase of the first cohort of 15 patients is being conducted across 11 clinical sites in Belgium, The Netherlands and Hungary. Recruitment of the last two patients in this cohort was completed in October. The first safety and pharmacokinetic data from these 15 patients is expected in late December 2016. As previously announced, AIPAC’s expected duration based on forecast recruitment times and patient follow up is approximately three years.
Prima also confirms that interim data from the first cohort of patients in its Phase I, TACTI-mel clinical trial of IMP321 together with KEYTRUDA for metastatic melanoma patients is also expected in late December 2016.

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On December 20, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused clinical stage biotechnology company, reported two patent allowances for imaging agents delivered via the company’s patented PDC platform (Filing, 8-K, Cellectar Biosciences, DEC 20, 2016, View Source [SID1234517150]). The United States Patent and Trademark Office ("USPTO") issued patent allowances covering method of use for CLR 124 in the detection of radiation- and chemo-insensitive cancer or cancer metastases. Concurrently, the Japanese patent office granted a composition of matter allowance covering two optical imaging agents in the CLR 1500 series.

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"While we remain focused on the development of our phospholipid drug conjugate, or PDC, delivery technology for therapeutic applications, our imaging assets and platform capability represents an excellent partnership opportunity," said Jim Caruso, president and CEO of Cellectar. "The continued expansion of our intellectual property portfolio provides additional protection and increases the value of our delivery platform to potential partners."

The USPTO allowance for CLR 124 pertains to the detection of radiation- and chemo-insensitive cancer or cancer metastasis specifically using PET, SPECT or gamma camera scintigraphy, as well as quantitative 3-D imaging with PET/MRI. These allowed claims are a continuation in part of US Patent No. 8,877,160 with coverage extending until March 2, 2025. The Japanese composition of matter allowance for the CLR 1500 series agents using the company’s PDC platform was allowed by the Japanese Patent Office for two additional optical imaging agents for intraoperative imaging of tumors and tumor margins. These CLR 1500 compounds are from a divisional application from JP 5702366 with coverage extending through May 11, 2030.

About Phospholipid Drug Conjugates (PDCs)

Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

On December 19, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported that the U.S. Food and Drug Administration (FDA) has approved FoundationFocus CDxBRCA for use as a companion diagnostic to aid in identifying women with ovarian cancer for whom treatment with Rubraca (rucaparib), a therapy developed by Clovis Oncology, Inc., is being considered (Press release, Foundation Medicine, DEC 19, 2016, View Source [SID1234517130]). FoundationFocus CDxBRCA is an FDA-approved tissue-based, genomic assay that uniquely detects tumor BRCA1 and BRCA2 mutations (may include both germline (inherited) and somatic (acquired)) in ovarian cancer. FoundationFocus CDxBRCA may help identify more women who could benefit from Rubraca therapy as compared to conventional testing methods that only identify germline BRCA1/2 mutations. Germline-only BRCA1/2 testing identifies approximately half of all BRCA1/2 mutations.i,ii

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Rubraca is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies, and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

"These simultaneous approvals by the FDA represent a step forward for women with advanced ovarian cancer, an area where there is a tremendous need for effective therapeutic approaches and efficient ways to identify those most likely to respond to PARP inhibitor therapy," said Michael Pellini, M.D., chief executive officer of Foundation Medicine. "This approval also represents a significant milestone for Foundation Medicine, one that underscores the quality and value of our molecular information solutions to inform patient care and to accelerate and streamline the therapeutic development programs of our biopharmaceutical partners."

Foundation Medicine and Clovis Oncology closely collaborated on a regulatory strategy to develop FoundationFocus CDxBRCA in parallel with the development of Rubraca. Tissue samples taken from individuals with ovarian cancer who enrolled in rucaparib clinical trials were analyzed by Foundation Medicine utilizing comprehensive genomic profiling (CGP) to identify biomarkers associated with a response to therapy. These molecular signatures of response informed the development of FoundationFocus CDxBRCA, which was utilized in Clovis’ pivotal trial, ARIEL2, to identify patients and accelerate recruitment into the study. The companies filed concurrent pre-market approval (PMA) and new drug application (NDA) submissions with the FDA earlier this year.

With this FDA approval, FoundationFocus CDxBRCA is the first validated, tissue-based assay developed from the Quality Systems Regulations (QSR)-compliant version of Foundation Medicine’s CGP assay, providing uniform analysis of all BRCA1/2 coding exons.

Dr. Pellini continued, "FDA approval of our first companion diagnostic assay also represents an important advance in our efforts to utilize our rigorously validated CGP approach to deliver a universal companion diagnostic assay. We believe this approach may enable the efficient delivery of personalized cancer care by eliminating the guesswork for physicians through a comprehensive view of companion diagnostic claims, as well as potential treatment options based on guidelines, peer reviewed literature and clinical trials."

As part of the company’s effort to develop a universal companion diagnostic, earlier this year, Foundation Medicine announced that FoundationOne, the company’s CGP assay for solid tumors, was accepted by the FDA and the Centers for Medicare and Medicaid Services (CMS) for Parallel Review. The FDA also granted Foundation Medicine’s request for review as part of its Expedited Access Pathway for breakthrough devices. If approved, FoundationOne would be an FDA-approved CGP assay that incorporates multiple companion diagnostics to support precision medicine in oncology, including an indication for use as a companion diagnostic across a diverse range of solid tumors, which is anticipated to include ovarian cancer.

More than 22,000 women will potentially be diagnosed with ovarian cancer in the U.S. during 2016.iii Ovarian cancer is the leading cause of female gynecologic cancer-related deathsiv and one in four women with ovarian cancer have a germline or somatic BRCA mutation.ii

About FoundationFocus CDxBRCA

Intended Use: FoundationFocus CDxBRCA is a next generation sequencing test for qualitative detection of BRCA1 and BRCA2 (BRCA1/2) alterations in formalin-fixed paraffin-embedded (FFPE) ovarian tumor tissue. The FoundationFocus CDxBRCA assay detects sequence alterations in BRCA1/2 genes. Results of the test are used as an aid in identifying ovarian cancer patients for whom treatment with Rubraca (rucaparib) is being considered. If a patient is positive for any of the deleterious alterations specified in the BRCA1/2 classification, the patient may be eligible for treatment with Rubraca. This assay is to be performed at Foundation Medicine, Inc., a single laboratory site located at 150 Second Street, Cambridge, MA 02141. For more information about FoundationFocus CDxBRCA assay, visit View Source

On December 19, 2016 Kancera AB (publ) reported that the drug candidate KAN0440567 quickly and effectively counteracts the kind of pain that results from chemotherapy and that often prevents effective treatment of cancer (Press release, Kancera, DEC 19, 2016, View Source [SID1234517128]). The results also indicate that the Kancera drug candidate inhibits the development of the nerve damage that causes pain.

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Kancera, in collaboration with Professor Malcangio at King’s College, London, showed that oral treatment with the fractalkine blocker KAN0440567 counteracts pain caused by vincristine. Vincristine is a chemotherapy agent used to treat cancers such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin’s disease, neuroblastoma and small cell lung cancer.

Pain resulting from chemotherapy often leads to cancer treatment needing to be reduced in intensity or being interrupted before the desired results are achieved (1). Every year about 1.7 million patients are treated with chemotherapy in the United States, Europe and Japan (2). Approximately 80% (3) of these are affected by nerve injury and subsequent pain and a significant proportion of these will have lasting problems that prevent a normal life. Today there is no effective treatment for this type of nerve damage.

In the Kancera study mice were treated with vincristine twice daily for five days, resembling the clinical protocol that can lead to nerve injury and pain. Oral treatment with KAN0440567, 125 mg/kg twice daily, effectively reduced the onset of this pain. From day one the effect was evident in the KAN0440567-treated animals and on days two to five pain was significantly lower than the control group. The study also showed that KAN0440567 did not affect sensitivity to being touched in the control animals, which supports the idea that the Kancera drug candidate specifically inhibits development of nerve damage.

If these effects are also achieved under clinical conditions, KAN0440567 could contribute to more effective cancer treatment since the desired dosage of chemotherapy can be maintained longer with less side effects in the form of nerve damage. Furthermore, reduced long-lasting nerve problems after successful cancer treatment would result in more patients being able to return to a normal life.

What makes KAN0440567 unique is that it works by preventing a special group of immune cells (monocytes) from infiltrating healthy tissue and causing damage, while other parts of the immune system maintain their protective ability. Thus, KAN440567 is likely to be effective in several inflammatory diseases, cancer and pain, without seriously affecting the immune system in general.

1. Windebank AJ and Grisold W (2008) J Per Nerv Syst 13: 27-46
2. IMS
3. Sisignano, M. et al. (2014) Nat Rev Neurol 10, 694–707

About the Fractalkine project Fractalkine is an immune regulatory factor, a so-called chemokine, that sends signals via the CX3CR1 receptor, also called G-protein coupled receptor 13 (GPCR13). The level of fractalkine and its receptor, CX3CR1 has been shown to be elevated in many inflammatory diseases, cancer and in chronic pain conditions. Kancera’s drug candidate KAN0440567 is the furthest developed drug candidate against CX3CR1 and has been shown to be effective against inflammation and pain in several preclinical disease models. Kancera is now preparing the project for clinical studies. In the healthy individual, Fractalkine and its receptor regulate migration of immune cells from the blood capillary wall into areas where the immune system is needed. Animal studies show that Fractalkine’s receptor is not essential for survival and that important immune functions remain intact despite the lack of receptor.The body of research supports the overall hypothesis that CX3CR1 is more crucial to developing disease than to keeping the individual healthy. The basis for successful development of KAN0440567 lies in effectively addressing local inflammation while maintaining a healthy immune system.

On December 19, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, and Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported that they have entered into a staged collaboration to evaluate, develop, and commercialize next-generation T-cell therapies (Press release, Adaptimmune, DEC 19, 2016, View Source [SID1234631816]).

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Under the agreement, the companies will evaluate Bellicum’s GoTCR technology (inducible MyD88/CD40 co-stimulation, or iMC) with Adaptimmune’s affinity-optimized SPEAR T-cells for the potential to create enhanced TCR product candidates. Depending on results from the preclinical proof-of-concept phase, the companies expect to progress to a two-target co-development and co-commercialization phase.

"We are committed to advancing our clinical pipeline of proprietary cell therapies and to entering strategic collaborations that can further leverage the unique potential of our controllable T-cell technologies," commented Tom Farrell, President and Chief Executive Officer of Bellicum. "We’re looking forward to working with the Adaptimmune team to create and advance potentially best-in-class TCR therapies."

"As we advance our deep pipeline of second- and third-generation SPEAR T-cell therapies, we are excited by the potential of Bellicum’s iMC switch to complement the activity of our affinity enhanced T-cell therapies, as part of our continuing initiative to assess novel cell therapy enhancement technologies," said James Noble, Adaptimmune’s Chief Executive Officer. "This is an innovative field that requires broad, industry-wide collaborations, such as our relationship with Bellicum and its strong leadership position in switch technology."

About Bellicum’s iMC Technology
Bellicum’s Chemical Induction of Dimerization (CID) technology platform was designed to address the challenges of current cellular immunotherapies by enabling control over cellular activities and functions, such as growth, activation, proliferation, persistence and survival. Bellicum’s CID platform consists of molecular switches—modified forms of signaling proteins—which are triggered inside the patient by infusion of small molecule rimiducid, instead of by natural upstream signals. Current product candidates incorporate either the CaspaCIDe safety switch, or iMC activation switch. After rimiducid is administered, CaspaCIDe is designed to trigger programmed cell death, or apoptosis, and iMC is designed to drive proliferation, activation and/or persistence of T-cells.

About Adaptimmune’s TCR Technology
Adaptimmune’s proprietary SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cell receptor (TCR) technology enables the Company to genetically optimize TCRs in an effort to equip them to recognize and bind cancer antigens that are presented in small quantities on the surface of a cancer cell, whether of intracellular or extracellular origin, thus initiating cell death. The Company’s differentiated, proprietary technology allows it to reliably generate parental TCRs to naturally presented targets, affinity optimize its TCRs to bind cancer proteins from solid and hematologic cancers that are generally unavailable to naturally occurring TCRs, and to significantly reduce the risk of side effects resulting from off-target binding of healthy tissues.