On September 23, 2015 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company ("Provectus" or the "Company"), reported it has completed development of the protocol for Phase1b/2 testing of its investigational cancer drug PV-10 in combination with pembrolizumab in patients with Stage IV melanoma (Filing, 8-K, Provectus Pharmaceuticals, SEP 23, 2015, View Source [SID:1234507527]). Pembrolizumab (also known as Keytruda, a product of Merck and Co. Inc., NYSE: MRK) is an immune checkpoint inhibitor approved for treatment of patients with advanced or unresectable melanoma. PV-10 is Provectus’s novel investigational drug for cancer that is injected into solid tumors (intralesional administration); it is currently undergoing Phase 3 clinical testing in patients with Stage III melanoma. Clinical testing under the new Phase 1b/2 protocol is expected to commence before the end of the year.

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The combination protocol enables initial clinical testing of concepts at the center of a patent held by Provectus, U.S. Patent number 9,107,887, which Pfizer, Inc. (NYSE: PFE) jointly owns. Specifically, the patent covers the use of PV-10 in combination with systemic inhibitors of immune system down-regulation, such as anti-CTLA-4, PD-1 and PD-L1 immune checkpoint inhibiting antibodies. Pembrolizumab is an anti-PD-1 antibody. Pre-clinical testing of PV-10 used in combination with these important classes of drugs demonstrated potential importance for treatment of advanced cancers.

The FDA granted accelerated approval to pembrolizumab in September 2014, making it the first FDA-approved anti-PD-1 immune checkpoint inhibitor. Because pembrolizumab is already FDA-approved, Provectus can commence this study with or without assistance of a partner.

The Phase 1b/2 study will incorporate a modest sized single arm Phase 1b component of 24 subjects with expedited safety and efficacy end points. This is designed to support expansion to a larger randomized Phase 2 component. Combined, these two arms will enable assessment of the potential safety and clinical benefit of PV-10 when used with pembrolizumab for treatment of advanced melanoma.

Dr. Eric Wachter, CTO of Provectus, stated, "The primary end point of tolerability in the Phase 1b portion of the study, combined with assessment of progression free survival (PFS) and objective response rate (ORR) by RECIST criteria as key secondary endpoints, assessed over a 15 week treatment interval, establish a basis for determining whether to proceed to the larger, randomized Phase 2 portion of the study. We will use an adaptive design for powering Phase 2 based on preliminary results from Phase 1, and estimate this portion of the study to require at least 120 subjects, with a primary endpoint of PFS and key secondary endpoint of ORR. In both portions of the study, pembrolizumab will be administered every three weeks for up to 24 months, as is standard of care; PV-10 will be administered on the same schedule for the first 15 weeks to all of the subject’s skin lesions. Subjects in Phase 1b will receive both PV-10 and pembrolizumab, whereas in Phase 2 subjects will be randomized to PV-10 + pembrolizumab or pembrolizumab alone."

Pete Culpepper, CFO and COO of Provectus, noted, "This study is both scientifically and commercially important to Provectus. Scientifically, combination therapy in cancer treatment is a rapidly maturing area, where rational combination of agents is replacing the empirical approaches of the past. Commercially, this is the second of three steps that we hope will significantly strengthen our hand in negotiating a co-development transaction with an immunotherapy-focused partner. Our joint patent with Pfizer was the first; this study is the second; and the third is our immune mechanism of action clinical study, which is underway at the Moffitt Cancer Center and which has completed recruitment."

The mechanism of action study’s preliminary clinical findings, reported last year, showed that the immunologic effects of tumor ablation with PV-10 may be complementary to immune checkpoint inhibition. Companion pre-clinical testing of PV-10 in murine models of melanoma, also reported last year, showed that the therapeutic effects of PV-10 and immune checkpoint inhibition are increased when the two are used in combination.

The cost of pembrolizumab is reimbursed so it is not paid for by Provectus and the remaining cost of this study is budgeted with existing cash on hand of the Company.

For further details on the protocol visit View Source

On September 24, 2015 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that it will highlight the ixazomib clinical development program during multiple poster sessions at the upcoming 15th International Myeloma Workshop (IMW 2015) to be held in Rome, Italy, from September 23 to 26, 2015 (Press release, Takeda, SEP 23, 2015, View Source [SID:1234507529]).

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"IMW presents an important opportunity for the multiple myeloma community to come together," said Dixie-Lee Esseltine, MD, FRCPC, Vice President, Oncology Therapeutic Area Unit, Takeda. "Ixazomib’s TOURMALINE program, which we anticipate will have over 3,000 patients when fully enrolled, is the embodiment of Takeda’s commitment to addressing the unmet needs in multiple myeloma, and now contains a pivotal trial in every major segment of this patient population. We look forward to presenting an overview of this program at IMW and engaging with our partners in the fight against multiple myeloma."

Ixazomib is currently under review with the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed and/or refractory multiple myeloma, and has been granted accelerated assessment and priority review, respectively. The regulatory submissions are based on the results of the first pre-specified interim analysis of the pivotal Phase 3 trial TOURMALINE-MM1, an international, randomized, double-blind, placebo controlled clinical trial of 722 patients designed to evaluate the superiority of once-a-week oral ixazomib plus lenalidomide and dexamethasone over placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Additional filings in other countries are planned to begin this year. Ixazomib is the first oral proteasome inhibitor in late stage clinical development for the treatment of patients with multiple myeloma.

Ixazomib presentations at IMW 2015 are as follows:

Format/Timing: Poster Discussion; Thursday, September 24, 2015 (6:40-7:40 p.m. CEST)
Abstract No: 0110
Abstract Title: Four Phase 3 Studies of the Oral Proteasome Inhibitor (PI) Ixazomib for Multiple Myeloma in the Newly-Diagnosed, Relapsed/Refractory, and Maintenance
Settings: Tourmaline-MM1, -MM2, -MM3, and -MM4
Authors: Jesus San Miguel, Philippe Moreau, Vincent Rajkumar, Antonio Palumbo, Thierry Facon, Gareth Morgan, Robert Orlowski, Michele Cavo, Hermann Einsele, Frank
Neumann, Richard Labotka, Sagar Lonial, Paul Richardson

Location: Poster Area, 1st Floor

Format/Timing: Poster Display; Friday, September 25, 2015 (6:40-7:40 p.m. CEST)
Abstract No: 0112
Abstract Title: The Current Unmet Medical Needs in the Treatment and Management of Multiple Myeloma (MM)
Authors: Paul Richardson, Antonio Palumbo, Maria-Victoria Mateos, Helgi van de Velde, Tomas Skacel, Sagar Lonial
Location: Poster Area, 1st Floor

Format/Timing: Poster Discussion; Thursday, September 24, 2015 (6:40-7:40 p.m. CEST)
Abstract No: 0167
Abstract Title: Phase 3 Study of the Oral Proteasome Inhibitor Ixazomib for Relapsed/Refractory AL Amyloidosis: TOURMALINE-AL1
Authors: Giampaolo Merlini, Angela Dispenzieri, Deborah Berg, Douglas V. Faller, Ai-Min Hui, Raymond L. Comenzo
Location: Poster Area, 1st Floor

Format/Timing: Poster Discussion; Friday, September 25, 2015 (6:40 – 7:40 p.m. CEST)
Abstract No: 0177
Abstract Title: Safety Profile of Oral Ixazomib: Experience from 761 Patients Across 14 Phase 1 or Phase 1/2 Clinical Studies
Authors: Sagar Lonial, Kathleen Colson, R. Donald Harvey, Shaji Kumar, Ai-Min Hui, Guohui Liu, Deborah Berg, Paul Richardson
Location: Poster Area, 1st Floor

About Ixazomib and the TOURMALINE Trials
Ixazomib is an investigational oral proteasome inhibitor which is being studied in multiple myeloma, systemic light-chain (AL) amyloidosis, and other malignancies. Ixazomib was granted orphan drug designation in multiple myeloma in both the United States and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials.

Ixazomib’s clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. Five global Phase 3 trials are ongoing:

TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT
TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis

For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.

About Multiple Myeloma
Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of plasma cells, or myeloma cells, becomes cancerous and multiplies, increasing the number of plasma cells to a higher than normal level. Because plasma cells circulate widely in the body, they have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anemia. Multiple myeloma is a rare form of cancer with approximately 39,000 new cases in the EU and 114,000 new cases globally per year.

On September 23, 2015 OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) reported initial results from the Phase 2 Rainier study evaluating apatorsen in combination with ABRAXANE (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) and gemcitabine compared to ABRAXANE and gemcitabine alone in patients with untreated metastatic pancreatic cancer (Filing, 8-K, OncoGenex Pharmaceuticals, SEP 23, 2015, View Source [SID:1234507534]). The addition of apatorsen to ABRAXANE and gemcitabine did not demonstrate a survival benefit compared to ABRAXANE and gemcitabine alone. The study was sponsored and conducted by Sarah Cannon Research Institute (SCRI) and further results will be presented by SCRI at a future medical meeting.

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Pancreatic cancer accounts for approximately 338,000 new cases each year worldwide. In the U.S., it continues to be the fourth leading cause of cancer death. Most pancreatic cancer patients will die within the first year of diagnosis, and five-year survival rates are less than 10 percent.

"Over the last decade, very few treatments have been able to demonstrate a survival benefit in this very difficult-to-treat cancer," said Johanna Bendell, MD, Director of the GI Cancer Research Program, SCRI, and a primary investigator on the trial. "We understand the dire need for new treatment options and are thankful to the patients who participated in this trial."
The most common grade 3/4 treatment-related toxicities on the apatorsen arm were anemia, neutropenia and fatigue, also consistent with the chemotherapy regimen side effects. These and other adverse events (AEs) observed on the apatorsen arm were similar to those seen in previous trials, with the exception of an increase in grade 4 or greater AEs and serious AEs in this pancreatic cancer trial. While patients in the apatorsen arm had fewer treatment discontinuations due to progressive disease, more patients discontinued therapy due to AEs.

"While we are disappointed with the Rainier results, we also recognize the challenges associated with developing effective treatments for such a lethal and complex disease. We remain confident in our broader apatorsen program, which includes ongoing Phase 2 clinical trials in lung, prostate and bladder cancers," said Scott Cormack, President and CEO of OncoGenex.

Recent Apatorsen Data
Results from an exploratory analysis of the Phase 2 Borealis-1 trial showed that patients with metastatic bladder cancer with poor prognostic features experienced a reduction in risk of death with the addition of 600 mg apatorsen added to first-line chemotherapy, compared to chemotherapy alone.

About Apatorsen and ORCA
Apatorsen (OGX-427) is a once-weekly intravenous (IV) experimental drug that is designed to inhibit production of heat shock protein 27 (Hsp27) to disable cancer cells’ defenses and overcome treatment resistance. Hsp27 in an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Both the potential single-agent activity and synergistic activity of apatorsen with cancer treatments may increase the overall benefit of existing therapies and augment the durability of treatment outcomes, which could lead to increased patient survival. The ORCA (Ongoing Studies Evaluating Treatment Resistance in CAncer) program encompasses clinical trials of apatorsen. For more information on apatorsen and ORCA, please visit www. OncoGenex.com or www.orcatrials.com.

On September 23, 2015 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported updated safety and preliminary efficacy data on its proprietary drug candidate MOR202 from an ongoing phase 1/2a study (Press release, MorphoSys, SEP 22, 2015, View Source [SID:1234507519]). MOR202 is a fully human HuCAL antibody targeting CD38, a highly expressed and validated target in multiple myeloma. The clinical data, which will be presented at the 15th International Myeloma Workshop in Rome, Italy, September 23th-26th, confirm the very good overall safety profile previously reported at this year’s ASCO (Free ASCO Whitepaper) meeting. The update also includes promising first results from the highest dose escalation cohort of 16 mg/kg of MOR202 weekly plus dexamethasone and from the recently initiated combination arms with the immunomodulatory drugs (IMiDs) pomalidomide and lenalidomide.

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As of August 24, 2015, 50 heavily pretreated patients with relapsed/refractory multiple myeloma had received MOR202 with and without dexamethasone and in a few cases in combination with pomalidomide or lenalidomide as part of a recently initiated second part of the study. MOR202 continued to demonstrate long-lasting tumor control, as well as signs of activity. In addition to the earlier reported very good partial response (VGPR) in a cohort dosed weekly with 4 mg/kg of MOR202 plus dexamethasone, a minor response (MR) in the 8 mg/kg MOR202 weekly plus dexamethasone cohort further improved into a partial response (PR). A first MR was observed in one patient in an ongoing cohort at the highest dose level, of 16 mg/kg MOR202 plus dexamethasone. The first evaluable patient in the ongoing combination cohort of 8 mg/kg MOR202 plus pomalidomide and dexamethasone achieved a PR already after the first cycle. In the ongoing combination cohort of 8 mg/kg MOR202 plus lenalidomide and dexamethasone, one patient showed a MR after the first cycle. In total, the data shows one VGPR, two PRs and two MRs so far.

"The MOR202 data have matured nicely since we presented the program at this year’s ASCO (Free ASCO Whitepaper) conference and we expect an even more comprehensive picture as the trial progresses. First results from the combination cohorts with lenalidomide and pomalidomide confirm the synergistic potential we have demonstrated in preclinical studies using our antibody together with these two IMiDs. This bodes well for the future development of MOR202," commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG.

The data to be presented at the International Myeloma Workshop 2015 show that MOR202 was safe and tolerable and could be administered as a 2-hour infusion. Infusion-related reactions occurred in 15 patients (30%). Only one out of these 15 patients received dexamethasone as co-medication and experienced an infusion-related reaction (grade 1). In the absence of dexamethasone, all infusion reactions were grade 1-2 except for one patient with grade 3, mainly limited to the first infusion. The maximum tolerated dose has not been reached.

"The antibody continues to show a balanced safety and tolerability profile and the preliminary efficacy seen so far with MOR202 as single agent and in combinations is promising. Considering the low rate of infusion reactions, even in cohorts without dexamethasone, the short infusion time and other aspects, MOR202 may turn out to be an excellent choice in terms of safety and tolerability," commented Dr. Marc-Steffen Raab, Group Leader Experimental Therapies for Hematologic Malignancies at the Heidelberg University Hospital and the German Cancer Research Center DKFZ.

The study is ongoing and MorphoSys plans to provide a further update at a medical conference later this year.

The IMW poster can be downloaded from the Company’s website:

Poster #0156

Raab et al.: A phase I/IIa study of the human CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma

The poster presentation will take place on Friday Sep 25th, 6:40pm to 7:40pm CEST.

On September 23, 2015 MedImmune, the global biologics research and development arm of AstraZeneca, and Tanabe Research Laboratories U.S.A., Inc. (TRL), a subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC), reported that they have entered into a strategic collaboration and licensing agreement under which TRL will use MedImmune’s pyrrolobenzodiazepine (PBD)-based warhead and linker technology to generate monospecific and bispecific antibody-drug conjugates (ADCs) for investigation in various cancers (Press release, Mitsubishi Tanabe Pharma, SEP 22, 2015, View Source [SID:1234507530]).

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Under the agreement, TRL will exclusively license MedImmune’s next generation PBDs. The companies will partner to combine MedImmune’s PBD technology with TRL’s antibodies to develop next generation ADCs against a number of cancer targets. MedImmune will receive an upfront payment, development and commercial milestone payments, as well as single digit royalties on worldwide net sales.

MTPC will be responsible for the pre-clinical research, development, manufacturing and later-stage activities, including global commercialization. MedImmune has the option to an exclusive license for the development and commercialization of the programs in the United States and Europe at the conclusion of a Phase Ib trial.

ADCs are a developing area of cancer drug technology that offers selective targeting of cancer cells. MedImmune’s proprietary PBD technology provides cytotoxic agents, or warheads, for attachment to specific cancer-targeting antibodies. This targeted ADC approach has the potential to optimize the delivery of the cancer drug to the tumor. MedImmune has an active internal ADC pipeline with candidates nearing the clinic, and TRL has an active program of mono- and bispecific-antibodies targeting cancer cells.

"We are very pleased to join forces with MedImmune to further exploit our proprietary tumor specific antibodies," said Naoki Sakurai, Ph.D, Chief Executive Officer, TRL. "This is an important start for our pioneering work in the field of mono- and bi-specific therapeutic ADCs and we are excited to explore innovative therapeutic approaches in collaboration with one of the world’s leading biotech companies," added Roland Newman, Ph.D., Chief Scientific Officer, TRL.

Ronald Herbst, Vice President, Oncology Research & Development, MedImmune, said, "Developing next generation antibody-drug conjugates, including our proprietary PBD technology, is one of our key strategic areas of focus in oncology. Today’s collaboration with Tanabe Research Laboratories supports our efforts to grow our ADC portfolio through both internal activities and external partnerships, with the goal of generating novel treatments to meaningfully improve the lives of cancer patients."