On December 20 2016 Opsona Therapeutics Ltd (‘Opsona’), the innate immune drug development company focused on novel therapeutic approaches to treat oncology, autoimmune and other inflammatory diseases, reported the preliminary results from its ongoing prospective, open label Phase I/II study being conducted with OPN-305 in secondline lower (Low and intermediate-1) risk myelodysplastic syndrome (MDS) which created interest when presented recently at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego by Prof Garcia-Manero from the MD Anderson Cancer Center (Press release, Opsona Therapeutics, DEC 20, 2016, View Source;n=154&a=130 [SID1234517143]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

OPN-305 is a novel proprietary humanized IgG4 monoclonal antibody (MAb) against Toll-Like Receptor 2 (TLR2), a key target within the innate immune system. Opsona has recently received orphan drug designation from the United States Food and Drug Administration for MDS.

The study in patients with lower risk, red cell transfusion dependent, MDS who have failed hypomethylating agents (HMA) ± an erythropoiesis stimulating agent is ongoing in collaboration with MD Anderson Cancer Center in Houston USA with additional sites now being added in the USA.

As of December 2016, 24 eligible patients have been enrolled, 11 at 5 mg dose and 13 at 10 mg/kg. A total of 15 (75%) patients are evaluable for response. Hematological improvement has been seen in 53% (8/15) with 3 (20%) patients achieving transfusion independence and of these 2/5 (40%) were receiving 10 mg/kg while on OPN-305 monotherapy. 12 patients remain on study.

Median age was 72 years (range 42-87). Nine (43 %) patients were classified as Low risk and 15 (63%) as Intermediate-1 risk by IPSS. Thirteen patients (61%) had diploid cytogenetics, 8 (38%) RAEB,5 (23%) RCMD, 3 (14%) RA, 2 (10%) RARS, and 1 (4%) 5q-, RCMD-RS, CMML.

The median number of prior HMA therapies was 2 (range 1-4) with a median duration of prior therapies from time of diagnosis to enrollment of 22.7 months (range 6.3-56.1). The median number of OPN-305 cycles administered is 5 (2-22) with 5 of 9 (55.5%) patients having received azacitidine add-back after 16 weeks of OPN-305 monotherapy. A total of 5 (29%) patients developed AEs related to OPN-305 all grade 1 with gastrointestinal disorders being the most frequent (23.5%). At this point, no significant drug related toxicity or unexpected infectious complications have been seen and combination with azacitidine has been well tolerated.

To date three (20%) patients were taken off study due to progression to AML and 4 (27%) due to no response all at the 5 mg/kg dose. There is no evidence of treatment related anti-drug antibodies or statistically significant dynamic changes in cytokines in any of the patients.

Myelodysplastic syndromes are a complex and heterogeneous group of bone marrow failure disorders characterized by ineffective hematopoiesis and poor prognosis. There is an urgent need for the development of well tolerated, novel therapies in the treatment of MDS which can delay progression, improve patient survival and quality of life and reduce the social and economic burden of transfusion dependence.

Commenting on today’s announcement Mary Reilly VP Pharmaceutical Development & Operations said "OPN-305 data emerging in this heavily pre-treated group of patients is very encouraging, the unmet need for a safe and tolerable product for this patient population is significant and we are happy to be in collaboration with the MD Anderson Cancer Center one of the leading clinical center’s in this hematological area"

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 Novocure (NASDAQ: NVCR) reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Optune (NovoTTF-100A) – Novocure’s Tumor Treating Fields (TTFields) delivery system – in the treatment of adult patients with supra-tentorial glioblastoma (GBM) following maximal safe surgical resection and radiation therapy (Press release, NovoCure, DEC 19, 2016, View Source [SID1234517132]). Novocure will prepare to submit an application for public reimbursement of Optune for newly diagnosed GBM in Japan.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The Japanese MHLW’s approval of Optune represents an important milestone for Novocure, enabling us to treat more patients who suffer from this aggressive disease," said Novocure CEO Asaf Danziger. "Optune in combination with temozolomide has been clinically proven to extend survival in patients with newly diagnosed GBM, and we look forward to making Optune available to newly diagnosed GBM patients in Japan."

Novocure established commercial operations in Japan in March 2015 after the MHLW approved Optune for the treatment of recurrent GBM. Approximately 1,500 patients are diagnosed with GBM in Japan each year.

"This approval is a significant moment for newly diagnosed GBM patients in Japan," said Ryo Nishikawa, MD, PhD, President of the Japanese Society of Neuro-Oncology and Professor of Saitama Medical University International Medical Center. "Optune provides patients with an additional treatment option, one that has been proven to extend survival."

The MHLW’s approval of Optune for the treatment of newly diagnosed GBM was supported by Novocure’s phase 3 pivotal EF-14 trial results, which showed significant extension of both progression free and overall survival in newly diagnosed GBM patients receiving Optune with temozolomide compared to temozolomide alone. Optune is the first MHLW-approved therapy in more than a decade to demonstrate statistically and clinically significant extension of survival in newly diagnosed GBM patients.

"We have been eagerly anticipating this day," said Shungo Matori, Novocure’s General Manager Japan and Representative Director of Novocure K.K. "Newly diagnosed GBM patients have experienced an unmet need for better treatment options. We are dedicated to making Optune available to all GBM patients who can benefit from our therapy in Japan."