On January 5, 2016 Cellectar Biosciences, Inc. (NASDAQ:CLRB), an oncology-focused biotechnology company reported data from the first cohort of patients enrolled in its orphan drug-designated Phase 1 study of CLR 131 in patients with relapsed or refractory multiple myeloma (Filing, 8-K, Cellectar Biosciences, JAN 5, 2016, View Source [SID:1234508665]).

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Based on safety and efficacy data from the first cohort, the trial’s Data Monitoring Committee approved enrollment of the second cohort of patients with a 50 percent escalation in dose level of CLR 131.

The primary objective of the multi-center, open label, Phase 1 dose escalation study is to characterize the safety and tolerability of CLR 131 in patients with relapsed or refractory multiple myeloma. Secondary objectives include establishment of the recommended Phase 2 dose, both with and without dexamethasone, as well as an assessment of therapeutic activity.

Prior to their participation in this study, patients in the first cohort had received a minimum of three systemic regimens and up to 12 lines of therapy.

"Judging by the results of the first cohort, I believe there is significant potential for CLR 131 as a safe and tolerable treatment modality for relapsed or refractory multiple myeloma," stated Sikander Ailawadhi, MD, senior associate consultant, Division of Hematology/Oncology, Department of Medicine, The Mayo Clinic, Jacksonville, Florida, and the site’s lead investigator. "I believe initiating the second cohort of the trial will provide additional useful information, both in terms of establishing an appropriate treatment dose, as well as further understanding the compound’s potential in this indication."

Data from the first cohort of patients in the Phase 1 study demonstrated safety and tolerability with a favorable adverse event profile. Additionally, stable disease was achieved in four of five treated patients with two of these patients maintaining stable disease throughout the 85-day study monitoring period.

"Importantly, these data collectively demonstrate safety and tolerability in heavily pre-treated multiple myeloma patients as well as provide promising signals of activity," said Jim Caruso, president and CEO of Cellectar Biosciences. "These early outcomes and feedback from the investigators are encouraging and we look forward to further evaluating CLR 131 in the second cohort to determine optimal dose and regimen. More globally, these results provide us with further confirmation on the utility of our PDC delivery platform, which we believe is instrumental to these outcomes."

The company is developing CLR 131, its lead radiotherapeutic phospholipid drug conjugate (PDC), for the treatment of multiple myeloma through the targeted delivery of iodine-131 to myelomatous cells.

On January 05, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED) reported the achievement of two milestones from Celgene Corporation and pre-announced its 2015 year-end pro-forma cash balance and key anticipated events for 2016 (Press release, OncoMed, JAN 5, 2016, View Source [SID:1234508664]).

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OncoMed achieved the $70 million safety milestone from Celgene based on an analysis of available Phase 1b and blinded interim Phase 2 clinical trial safety data associated with the demcizumab (anti-DLL4, OMP-21M18) program. The data from the pancreatic, non-small cell lung and ovarian cancer clinical trials showed no demcizumab-related Grade 3 or higher cardio-pulmonary toxicities among 155 patients treated with truncated dosing. Of those, 68 patients have received at least two cycles of demcizumab at the Phase 2 dose or higher and have been followed for at least 100 days. OncoMed also achieved a $2.5 million milestone for clinical candidate designation of an undisclosed preclinical immuno-oncology program, "IO#2". This is OncoMed’s second immuno-oncology program to reach clinical candidate designation, and both programs are advancing in IND-enabling studies.

Including the Celgene milestones, OncoMed ended 2015 with approximately $227.2 million in pro-forma cash, representing approximately 1.5 years of cash, without taking into account future potential milestone payments from partners, and exceeding its 2015 guidance predicting a year-end cash balance of greater than $120 million. Full-year operating expenses for 2015 are anticipated to be approximately $110 million, in accordance with previous guidance. OncoMed plans to provide full-year 2016 guidance during its 2015 fourth quarter earnings call in the first quarter of 2016.

"The achievement of the demcizumab $70 million safety milestone is based on extensive Phase 1b and blinded Phase 2 data, and positions OncoMed to rapidly enroll its Phase 2 randomized YOSEMITE and DENALI clinical trials, as well as the Phase 1b demcizumab plus pembrolizumab (anti-PD1) trial, and also to explore the potential of demcizumab in ovarian cancer," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "We enter 2016 in a strong cash position to support all seven internally discovered programs through clinical trials, including four randomized Phase 2 clinical studies, and to advance two immuno-oncology candidates toward IND filings while maintaining ongoing discovery efforts. Over the course of this year, we anticipate completing and reporting on our first randomized Phase 2 clinical trial, the tarextumab ALPINE study in pancreatic cancer, presenting additional data from our ongoing clinical- and discovery-stage programs, filing at least one new IND and achieving additional milestones related to our collaborations."

2016: Anticipated Key Financial Milestones and Pipeline Progress by Program

Demcizumab (anti-DLL4, OMP-21M18)

Present updated Phase 1b survival data for demcizumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in previously untreated pancreatic cancer at the Gastrointestinal Cancer Symposium (ASCO GI) being held January 21-23, 2016 in San Francisco, CA. OncoMed’s presentation, titled "A Phase 1b study of the anti-cancer stem cell agent demcizumab (DEM) and gemcitabine (GEM) +/- nab-paclitaxel in patients with pancreatic cancer (Abstract 341)," will be presented by Dr. Manuel Hidalgo during Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract on Friday, January 22, 2016.
Initiate Phase 1b clinical trial of demcizumab plus anti-PD1 pembrolizumab in the first quarter of 2016.
Update survival data from the demcizumab Phase 1b non-small cell lung cancer (NSCLC) clinical trial.
At the ASCO (Free ASCO Whitepaper) meeting in June 2015, OncoMed reported Phase 1b clinical trial data in NSCLC for 23 advanced-stage patients who received continuous dosing of demcizumab plus standard-of-care chemotherapy. These data showed that 43 percent (10 of 23) of patients were alive past two years, demonstrating prolonged survival in this subset of patients. A recent update of continuous dosing data revealed one additional death with 39 percent (9 of 23) of patients alive past 2 years.

In August, 2015, OncoMed updated survival data for 23 patients who received truncated doses of demcizumab plus chemotherapy and were showing a similar trend toward improved survival. At that time, fifty-two percent (12 of 23) of patients who received truncated doses of demcizumab plus carboplatin and pemetrexed remained alive from 8-30 months after initial dosing. A recent update of these data has revealed four additional deaths. Currently, 35 percent (8 of 23) of patients remain alive between 12 and 34 months after the initiation of treatment and median overall survival is 11.6 months. Although these data represent a Phase 1b clinical trial in small numbers of patients, they suggest that a subset of patients treated with the demcizumab truncated dosing regimen in NSCLC continues to derive long-term benefit. These data continue to support and enable the current randomized Phase 2 "DENALI" trial.

Complete enrollment in the randomized Phase 2 "YOSEMITE" clinical trial of demcizumab in combination with Abraxane and gemcitabine in patients with first-line pancreatic cancer by year end. Data from this study are expected to be available by early 2017.
Continue enrollment in the Phase 2 "DENALI" clinical trial of demcizumab plus carboplatin and pemetrexed in first-line non-squamous NSCLC.
Report results from the ovarian cancer Phase 1b trial of demcizumab plus paclitaxel.
The next potential financial milestone for demcizumab is an opt-in payment from Celgene that may occur through the end of either of the Phase 2 pancreatic cancer or NSCLC trials. Following option exercise, OncoMed and Celgene will co-develop and co-commercialize demcizumab in the U.S., sharing profits 50/50, while Celgene would lead development and commercialization outside the U.S.

Tarextumab (anti-Notch 2/3, OMP-59R5)

Present updated survival data from the Phase 1b clinical trial of tarextumab plus chemotherapy in small cell lung cancer at the time of the IASLC 16th Annual Targeted Therapies of Lung Cancer Meeting being held February 17-21, 2016.
Report top-line results from the Phase 2 "ALPINE" clinical trial of tarextumab in combination with Abraxane plus gemcitabine in advanced pancreatic cancer during the second half of 2016.
GlaxoSmithKline (GSK) may exercise the option for tarextumab through the end of either of the randomized Phase 2 clinical trials in pancreatic or small cell lung cancers. If GSK elects to exercise its option, OncoMed is eligible to receive a $25 million payment, and GSK would lead and fully fund further development and commercialization.

Wnt programs — Vantictumab (anti-Fzd7, OMP-18R5) and Ipafricept (Fzd8-Fc, OMP-54F28)

Advance vantictumab and ipafricept through multiple ongoing Phase 1b clinical studies.
Bayer can elect to exercise its options on vantictumab and ipafricept at any point through completion of Phase 1b trials. OncoMed and Bayer amended their agreement November 2015 to enroll up to 24 additional subjects in the ongoing Phase 1b clinical trials of vantictumab in breast cancer and ipafricept in ovarian cancer. Bayer has agreed to reimburse OncoMed for all out-of-pocket expenses to support this additional patient enrollment. OncoMed anticipates presenting opt-in packages to Bayer for both vantictumab and ipafricept in late 2016/early 2017.

Brontictuzumab (anti-Notch1, OMP-52M51)

Initiate Phase 1b clinical trial of brontictuzumab combined with FOLFIRI in colorectal cancer patients including an expansion cohort of biomarker-selected subjects based on promising data presented in November 2015 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper).
GSK may currently elect to opt in brontictuzumab at the end of Phase 1a, for a fee of $18.75 million or at the conclusion of Phase 2 for a fee of $25 million. GSK and OncoMed have agreed to share out-of-pocket costs on the Phase 1b clinical trial described above, and are currently discussing a potential extension of GSK’s Phase 1a option through the end of Phase 1b.

Anti-DLL4/VEGF bispecific (OMP-305B83)

Aim to present data from the Phase 1a dose-escalation clinical trial of anti-DLL4/VEGF bispecific. Presentation of data will be contingent on the number of dose cohorts needed to identify a Phase 2 single-agent dose and abstract acceptance at a scientific conference.
Through the conclusion of the Phase 1a and 1b clinical trials, Celgene may exercise its option to co-develop and co-commercialize anti-DLL4/VEGF bispecific.

Anti-RSPO3 (OMP-121R10)

Initiate enrollment of Phase 1a biomarker-selected expansion cohort
Aim to present Phase 1a data at an upcoming medical meeting in the second half of 2016, contingent upon dose-escalation and abstract acceptance.
Initiate enrollment of Phase 1b component in the first-in-human trial of anti-RSPO3 in combination with FOLFIRI chemotherapy in subjects with colorectal cancer including biomarker-positive subjects.
As with the anti-DLL4/VEGF bispecific, Celgene may exercise its option to co-develop and co-commercialize anti-RSPO3 through the conclusion of the Phase 1 clinical trial.

Immuno-oncology Pipeline

Advance either the immuno-oncology product candidate that is part of OncoMed’s collaboration with Celgene (IO#2) or OncoMed’s wholly owned GITRL-Fc program to an Investigational New Drug (IND) application filing by the end of 2016. Both programs are currently advancing in IND-enabling preclinical studies.
OncoMed estimates that over the course of the next two-to-three years (2016, 2017 and 2018), the company may be eligible to receive more than $168 million in potential opt-in payments from its collaboration with Celgene, $60 million in potential opt-in and milestone payments from Bayer and $43 million in potential opt-in payments from GSK. Overall, in future years, OncoMed is eligible for more than $5 billion in total potential milestone and option payments from its partners under its collaboration agreements with Celgene, Bayer, and GSK. To date, OncoMed has received over $450 million from its existing partners.

On January 05, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that two patents have been issued by the U.S. Patent and Trademark Office covering composition and methods related to its LADD and GVAX immunotherapy technologies (Press release, Aduro BioTech, JAN 5, 2016, View Source [SID:1234508662]).

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Patent 9,198,960 claims methods for enhancing an immune response to mesothelin by administering first a "prime" dose of an inactivated tumor cell containing a nucleic acid that encodes granulocyte macrophage-colony stimulation factor (GM-CSF) followed by a "boost" dose of an immunotherapy comprising an attenuated Listeria that encodes an expressible, immunologically active portion of mesothelin. The patent also specifically claims the method for Aduro’s live attenuated double deleted (LADD) platform containing deletions of the actA and inlB genes within Listeria. The nominal expiration date for this patent is July 17, 2027, subject to any extensions that may be available. Aduro has demonstrated in a randomized 93-patient Phase 2a clinical trial in metastatic pancreatic cancer that the claimed prime-boost approach utilizing its LADD and GVAX immunotherapies resulted in significant improvement in overall survival when compared to GVAX alone. The company is currently evaluating this regimen against single agent chemotherapy in the randomized Phase 2b ECLIPSE trial and also in combination with the PD-1 immune checkpoint blocker, nivolumab in the randomized Phase 2b STELLAR trial.

Patent 9,200,057, which is jointly owned with Providence Health & Services, claims compositions containing a bacterium or virus which comprises a nucleic acid encoding at least three copies of an EGFRvIII polypeptide, a tumor-specific neo-antigen, which facilitates both antigen expression levels and immunogenicity. Aduro is collaborating with Providence on an investigator-sponsored trial of its LADD immunotherapy containing EGFRvIII and NY-ESO-1, ADU-623 for which Aduro has exclusive rights, to evaluate treatment of high-grade glioma, a form of brain cancer. The EGFRvIII tumor-associated antigen is also being utilized by Aduro for other exclusively-owned LADD-based vaccine strains directed to additional cancer types. The nominal expiration date for this patent is November 17, 2031, subject to any extensions that may be available.

"These two patents are important expansions of our patent estate, encompassing claims associated with our therapeutic approaches and extending patent coverage into 2031," said Thomas Dubensky, Jr., chief scientific officer of Aduro. "These newly issued patents are illustrative of our objective to maintain a leadership position and we look forward to continued advancements, including key data announcements from randomized studies this year."

About LADD

LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. The LADD technology has been applied to several novel compounds in clinical and preclinical testing including CRS-207 (pancreatic cancer, mesothelioma and ovarian/fallopian/peritoneal cancer (collaboration with Incyte Corporation to be tested in combination with epacadostat)), ADU-623 (brain cancer), ADU-214 (lung cancer, licensed to Janssen Biotech, Inc.) and ADU-741 (prostate cancer, licensed to Janssen Biotech, Inc.).

About GVAX

GVAX a family of immunotherapies derived from human cancer cell lines that are genetically modified to express granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune system-stimulating cytokine. GVAX Pancreas, the company’s lead approach in this platform, is derived from human pancreatic cancer cell lines and is designed to activate specific T cell immunity to pancreatic cancer antigens, including mesothelin.

On January 5, 2016 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) and Baxalta Incorporated (Baxalta) (NYSE: BXLT) reported the completion of the rolling submission of the New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R (Press release, CTI BioPharma, JAN 5, 2016, View Source [SID:1234508660]).

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CTI BioPharma and Baxalta are requesting U.S. marketing approval of pacritinib for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/μL) – a specific patient population for which there is an existing unmet medical need. The Companies are seeking accelerated approval and have requested a Priority Review of the application.

Pacritinib is an investigational treatment being developed for patients with myelofibrosis regardless of their platelet counts. If approved, pacritinib would be the first JAK2 inhibitor indicated for the treatment of patients with myelofibrosis and baseline platelet counts of less <50,000/μL.

"We are pleased to have completed the rolling submission and look forward to working with the FDA during the review process with the goal of bringing this important treatment to people living with myelofibrosis, including those with low platelet counts," said James Bianco, M.D., president and chief executive officer of CTI BioPharma.

Myelofibrosis is a rare, but serious and life-threatening chronic leukemia that disrupts the normal production of blood cells and results in scarring of the bone marrow, limiting the ability to produce new blood cells and prompting the spleen and other organs to take over this function. The disease often leads to an enlarged spleen and lower than normal counts of blood cells – including red blood cells and platelets, which are essential for blood clotting.

"Pacritinib has the potential to change the treatment paradigm for people with intermediate and high-risk myelofibrosis, particularly those patients with cytopenias," said David Meek, executive vice president, president of Oncology at Baxalta. "Together with CTI BioPharma, we are continuing to develop this potential new treatment for more people in need around the world."

About the Pacritinib NDA
The NDA includes data from the PERSIST-1 Phase 3 trial – as well as data from Phase 1 and 2 studies of pacritinib. Submission of an NDA after a single Phase 3 trial under accelerated approval, instead of waiting to complete two Phase 3 trials, could potentially reduce time to market by up to 14 months. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high-risk myelofibrosis including, but not limited to, patients with disease-related thrombocytopenia (low platelet counts); patients experiencing treatment emergent thrombocytopenia on another JAK2 therapy; or patients who are intolerant to or whose symptoms are not well controlled (or sub-optimally managed) on another JAK2 therapy.

CTI BioPharma and Baxalta are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.

About Myelofibrosis and Myeloproliferative Neoplasms
Myelofibrosis is one of three main types of myeloproliferative neoplasms (MPN), which are a closely related group of hematological blood cancers. The three main types of MPNs are myelofibrosis, polycethemia vera and essential thrombocythemia.1

Myelofibrosis is a serious and life-threatening chronic bone marrow disorder caused by the accumulation of malignant bone marrow cells that triggers an inflammatory response and scars the bone marrow. The replacement of bone marrow with scar tissue limits its ability to produce red blood cells, prompting the spleen and liver to take over this function. Symptoms that arise from this disease include enlargement of the spleen, anemia, extreme fatigue, and pain.

The estimated prevalence of MPNs suggest there are approximately 300,000 people living with the disease in the U.S., of which myelofibrosis accounts for approximately 18,000 patients.2 In Europe, there is a wide variation of prevalence observed across data sources. Myelofibrosis has a median age of 64 at the time of diagnosis2 and is a progressive disease with approximately 20 percent of patients eventually developing AML.3 The median survival for high-risk myelofibrosis patients is less than one and a half years, while the median survival for patients with myelofibrosis overall is approximately six years.4