(Filing, 10-Q, BioTime, NOV 9, 2015, View Source [SID:1234508133])

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(Filing, 10-Q, Navidea Biopharmaceuticals, NOV 9, 2015, View Source [SID:1234508168])

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On November 9, 2015 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a clinical-stage pharmaceutical company, reported financial results for the third quarter 2015 and commented on recent accomplishments and clinical development plans for its pipeline of SINE-based therapeutics including selinexor, its lead product candidate (Filing, 8-K, Karyopharm, NOV 9, 2015, View Source [SID:1234508114]).

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"This has been a very busy period for Karyopharm with active enrollment across our ongoing selinexor clinical studies and new studies, primarily in combination with other anticancer agents, continuing to come on-line," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We look forward to sharing additional data on our pipeline of first-in-class oncology therapeutics at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) 2015 annual meeting, including selinexor activity in combination regimens across hematologic malignancies."

Conference Call Information:

Karyopharm will host a conference call today, Monday, November 9, 2015, at 8:30 a.m. Eastern Time, to discuss the third quarter 2015 financial results, recent accomplishments and clinical developments plans. To access the conference call, please dial (855) 437-4406 (US) or (484) 756-4292 (international) at least five minutes prior to the start time and refer to conference ID: 69164993. An audio recording of the call will be available under "Events & Presentations" in the Investor section of Karyopharm’s website, View Source, approximately two hours after the event.
Clinical Development Plans:

• Based on striking preclinical synergy in animal models of myeloma, Karyopharm initiated a multi-center, Phase 1b/2 clinical study of selinexor called STOMP ("Selinexor and Backbone Treatments of Multiple Myeloma Patients") with support from Myeloma Canada. In this multi-arm study, Karyopharm is evaluating the combination of selinexor and low dose dexamethasone with backbone therapies bortezomib, pomalidomide or lenalidomide in patients with previously treated multiple myeloma. Approximately 220 patients with multiple myeloma will be enrolled in this study with preliminary top-line data anticipated in 2017. Selinexor and low dose dexamethasone are already being combined with carfilzomib in an Investigator-sponsored trial (IST), where promising preliminary data were presented at the ASH (Free ASH Whitepaper) 2014 annual meeting and will be updated with additional patient data at the ASH (Free ASH Whitepaper) 2015 annual meeting.

• Karyopharm is actively enrolling patients in four later phase clinical studies evaluating single-agent selinexor: one in older patients with relapsed/refractory acute myeloid leukemia (SOPRA study), the second in patients with relapsed/refractory diffuse large B-cell lymphoma (SADAL study), the third in patients with multiple myeloma (STORM study) and the fourth in patients with Richter’s transformation (SIRRT study). Interim data are expected from the SOPRA and STORM studies in the middle of 2016. Preliminary top-line data from the SOPRA and SADAL studies are anticipated in the fourth quarter of 2016.

Targeting Disease at the Nuclear Pore

• Karyopharm is currently conducting company-sponsored trials of single-agent selinexor in three solid tumor indications including heavily pretreated patients with gynecologic malignancies (SIGN study), recurrent glioblastoma multiforme (KING study) and hormone-refractory prostate cancer (SHIP study). Based on promising data observed in a Phase 1 study, a randomized, blinded Phase 2/3 trial of selinexor versus placebo in liposarcoma (SEAL study) is planned to commence in the fourth quarter of 2015.

• In addition, a number of ISTs or company-sponsored trials evaluating the potential of selinexor in combination with either chemotherapy or targeted agents are currently ongoing or planned.

• Based on promising preclinical data, Karyopharm filed an Investigational New Drug (IND) application with the Food and Drug Administration (FDA) for KPT-8602 and, pending review, plans to initiate a clinical study in multiple myeloma in early 2016.

• Karyopharm also plans to file an IND for its first-in-class, oral PAK4 Allosteric Modulator, KPT-9274, and initiate clinical development in patients with heavily pretreated solid tumors or lymphoma in the first half of 2016.
Scientific Presentations and Publications:

• Five oral presentations and twelve poster presentations describing Karyopharm’s pipeline of first-in-class oncology therapeutics were accepted for presentation at the upcoming 57th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) 2015 meeting being held December 5 – 8, 2015 in Orlando, Florida. The accepted abstracts include:

• Clinical and preclinical data demonstrating the promising activity of selinexor (KPT-330), Karyopharm’s most advanced, novel, oral Selective Inhibitor of Nuclear Export/SINE compound, in combination with other anti-cancer agents;

• Preclinical data on KPT-8602, a second generation SINE compound in early-stage development with the potential for distinct pharmaceutical characteristics; and

• Preclinical data on KPT-9274, a first-in-class oral PAK4 Allosteric Modulator.

• Preclinical data demonstrating the anti-tumor benefits of combining selinexor with immunotherapy in aggressive melanoma models were presented at the Society for Immunotherapy Cancer (SITC) (Free SITC Whitepaper) 2015 Annual Meeting held November 4 – 8, 2015 in National Harbor, Maryland. In an oral presentation entitled "Selinexor, a Selective Inhibitor of Nuclear Export (SINE), enhanced activity in combination with PD-1/PD-L1 blockade in syngeneic murine models of colon cancer and melanoma" Karyopharm researchers and collaborators at The Ohio State University demonstrated that the combination of selinexor with PD-1 or PDL-1 immune checkpoint inhibitors exerts considerable anti-tumor and immune-stimulating activity in an aggressive murine melanoma model.

• Data demonstrating the beneficial pharmacological effects of SINE-based compounds in neurodegenerative models, including Amyotrophic Lateral Sclerosis (ALS), were recently published in the journal Nature and presented at the American Neurological Association (ANA) and the Society for Neuroscience (SfN) meetings. These data confirm that nuclear transport is disrupted by a common gene mutation found in ALS and describe the neuroprotective effects of SINE compounds, similar to the neuroprotective effects previously observed in Multiple Sclerosis (MS). Karyopharm’s SINE compound research efforts in ALS are being supported entirely by collaborator grant funding, with MS research supported by the National Multiple Sclerosis Society. Given the tremendous unmet need for new treatments for ALS and MS, Karyopharm is advancing its oral SINE compound KPT-350 for these indications.

Targeting Disease at the Nuclear Pore

Third Quarter September 30, 2015 Financial Results
Cash, cash equivalents and investments as of September 30, 2015, including restricted cash, totaled $230.2 million, compared to $256.0 million as of June 30, 2015.

For the quarter ended September 30, 2015, research and development expense was $25.9 million compared to $16.0 million for the quarter ended September 30, 2014. For the quarter ended September 30, 2015, general and administrative expense was $4.8 million compared to $3.8 million for the quarter ended September 30, 2014. The increase in research and development expense resulted primarily from the increase in expenses related to the continued clinical development of selinexor. The increase in general and administrative expense resulted primarily from the costs of being a public company and an increase in stock-based compensation.

Karyopharm reported a net loss of $30.4 million, or $0.85 per share, for the quarter ended September 30, 2015, compared to a net loss of $19.7 million, or $0.61 per share, for the quarter ended September 30, 2014. Net loss includes stock-based compensation expense of $3.5 million and $2.9 million for the quarters ended September 30, 2015 and September 30, 2014, respectively.

Financial Outlook
Based on current operating plans, Karyopharm expects that its existing cash and cash equivalents will fund its research and development programs and operations into 2018, including moving the four later-stage clinical studies to their next data inflection points. Karyopharm expects to end 2015 with greater than $200 million in cash, cash equivalents and investments.

On November 09, 2015 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body’s immune system to fight cancer, reported results from multiple new preclinical studies demonstrating enhanced anti-tumor activity and immune activation for combinations of a preclinical bavituximab equivalent and checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 in preclinical models of breast cancer and melanoma (Press release, Peregrine Pharmaceuticals, NOV 9, 2015, View Source [SID:1234508140]). Additionally, the company announced preliminary results for a new clinical test specifically designed to illustrate how bavituximab, the company’s investigational phosphatidylserine (PS)-signaling pathway inhibitor, modulates immune responses in the tumor microenvironment. Results from these studies were presented at the 2015 annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), which was held in National Harbor, MD, on November 4 – 8, 2015.

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"The positive data presented at SITC (Free SITC Whitepaper) with regard to combinations of bavituximab and checkpoint inhibitors further support our belief that bavituximab has the potential to be a critical component of innovative combination cancer immunotherapies," said Jeff T. Hutchins, vice president preclinical development of Peregrine. "Particularly exciting is the new data in animal models of breast cancer which showed that a significantly greater number of subjects demonstrated anti-tumor activity when treated with the combination of bavituximab and anti-PD-1 as compared to treatment with anti-PD-1 alone. Additionally, combination treatment led to prolonged protection for animals as evidenced by their lack of new tumor development when later re-challenged with the same tumors."

Bavituximab is an investigational immunotherapy designed to assist the body’s immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine’s PS signaling pathway inhibitor candidates, including bavituximab, reverse the immunosuppressive environment that many tumors establish in order to proliferate, while also fighting cancer by activating immune cells that target and fight cancer. The preclinical equivalent of bavituximab, ch1N11, is used in animal model studies as a guide for clinical development.

Breast Cancer
Researchers from Duke University and Peregrine evaluated the combination of ch1N11 (preclinical bavituximab equivalent) and anti-PD-1 therapy versus anti-PD-1 stand-alone therapy in well-characterized murine breast cancers, including the triple negative breast cancer (TNBC) model E0771. Study data showed that the combination therapy significantly enhanced overall survival (p=0.0016) and was capable of mediating complete tumor regressions in a greater number of subjects compared to single agent treatments (60% vs. 20%). Data also demonstrated that animals receiving combination treatment had significant increases in tumor associated indicators of immune system activation, including CD45+, CD8+ and CD3+ T-cells. Importantly, the combination treatment led to a prolonged anti-tumor immune response which protected the animals against a re-challenge with the same tumor. This sustained anti-tumor response suggests the potential of the combination therapy to trigger immune system memory and support adaptive immune responses against reemerging disease in breast cancers. All study animals experienced no signs of adverse effects following repeated doses of all therapeutic agents.

Melanoma
In follow-on work, researchers from the University of Texas, Southwestern and Peregrine evaluated combinations of ch1N11 and checkpoint inhibitors (anti-PD-1 or anti-CTLA-4) versus each agent as a stand-alone therapy in common models of melanoma (B16F10 and K1735). Data showed that the combinations of ch1N11 with either anti-PD-1 or anti-CTLA-4 led to significantly greater levels of tumor infiltrating CD8+ T cells than any of the three agents alone. Additionally, findings demonstrated that the combination therapies were more effective at shifting the tumor microenvironment from immunosuppressive to immune active than the single agents, as shown by greater increases in the ratio of T effector cells to T regulatory cells, reactivation of tumor infiltrating T cells and restoration of the effector function of the tumor infiltrating T cells. This activity was more pronounced for the ch1N11/anti-PD-1 combination than for the ch1N11/anti-CTLA-4 combination. Based on these data, study investigators concluded that ch1N11 synergizes with checkpoint inhibitors to induce strong tumor specific CD8 T cell immunity.

"There is an extensive and growing collection of data that demonstrates that phosphatidylserine directly triggers broad immunosuppression in the tumor microenvironment and contributes to resistance to checkpoint inhibitor therapy. By targeting and blocking PS, bavituximab appears able to shift the tumor environment from immunosuppressive to immune active and, in turn, enhance the anti-tumor activity of checkpoint inhibitors such as anti-PD-1 and anti-CTLA4," said Bruce Freimark, Ph.D., director of pre-clinical oncology of Peregrine. "This latest data in well validated models of multiple tumor types further support our belief that bavituximab may be able to play an essential role in combination immuno-oncology treatment regimens. With this in mind, we are committed to evaluating the agent’s potential in combination with a range of cancer therapies against various cancer types."

ImmunoProfiling
Researchers presented preliminary results for a new custom assay designed to provide detailed profiles of immune activity in patient tumors. The Opal 6-plex quantitative immunofluorescence (IF) assay is specifically designed to measure the level and type of lymphocytes, myeloid and dendritic cell subsets found within the tumor microenvironment. This information is important as it can be used to correlate immune response parameters with bavituximab treatment outcome and patient survival.

Presented results demonstrated that the Opal assay could reliably detect, measure and phenotype lymphocytes and monocytes present in tumor tissues from rectal adenocarcinoma, hepatocellular carcinoma and advanced melanoma patients treated with bavituximab combination therapies. Importantly, the findings were able to show changes in key indicators of immune activation, including CD8+, CD4+ and regulatory T-cells, as well as myeloid and dendritic cells, in the tumor microenvironment following bavituximab treatment. The ability of this new assay to accurately measure specific immune responses is expected to provide important additional information to assist in Peregrine’s ongoing development efforts for bavituximab. This will be particularly valuable as the company works to better elucidate the connection between the drug candidate’s impact on immunomodulation and patient response to treatment.

"We are very pleased with the performance of the Opal assay, particularly its ability to compare the interaction of up to six phenotypic and functional markers on a single slide of tissue. The power and prognostic value of such immune activity assessments in the area of cancer was initially established by the Immunoscore, and we believe the Opal assay represents an important evolution of that work," said Bernard A. Fox, Ph.D., Harder Family Endowed Chair for Cancer Research, Member and Chief, Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center; a world-renowned translational cancer immunotherapist; a founding member of the Immunoscore steering committee. "I am looking forward to continued collaboration with Peregrine to further optimize and validate this assay to improve our understanding of immune infiltrate in tumors thereby facilitating the rational design and use of bavituximab in combination with novel and standard therapies."

About Bavituximab: A Targeted Investigational Immunotherapy
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine’s immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.

(Filing, 10-Q, Curis, NOV 9, 2015, View Source [SID:1234508134])

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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

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