On November 09, 2015 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) reported results of operations for the quarter and nine months ended September 30, 2015 (Press release, Progenics Pharmaceuticals, NOV 9, 2015, View Source [SID:1234508141]).

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"We had a highly productive quarter, with positive regulatory developments, key additions to our pipeline and continued clinical progress," stated Mark Baker, CEO of Progenics. "The Breakthrough Therapy Designation for ultra-orphan candidate AzedraTM provides for an expedited development and review process, while the April 2016 PDUFA date for Oral RELISTOR establishes a pivotal near-term catalyst for our RELISTOR franchise. We acquired PyL, an imaging agent which is highly complementary with our 1404 program, establishing the leading portfolio of prostate cancer imaging agent candidates. In addition, our acquisition of EXINI will provide us with software development expertise to help further build our imaging toolkit for prostate cancer. We are well-positioned as we approach critical clinical milestones in the fourth quarter, including the completion of enrollment in our pivotal Phase 2b trial for Azedra and the launch of our Phase 3 program for 1404."

Net loss for the quarter was $10.0 million or $0.14 per diluted share, compared to net income of $37.0 million or $0.51 per diluted share in the third quarter of 2014. Net loss for the current nine months was $32.0 million, or $0.46 per diluted share, compared to net income of $16.6 million or $0.24 per diluted share in 2014. Progenics ended the quarter with cash and cash equivalents of $90.4 million, a decrease of $8.9 million in the quarter and $28.9 million from 2014 year-end.

Third quarter revenue totaled $1.4 million, down from $41.7 million in the third quarter of 2014, reflecting a decrease in collaboration revenue for RELISTOR (methylnaltrexone bromide) of $39.8 million, primarily resulting from the recognition of $40.0 million milestone from Salix and royalty income of $1.2 million compared to $1.6 million in the corresponding period in 2014, based on net sales reported to Progenics by our commercialization partner, Valeant Pharmaceuticals International, Inc. The current quarter decrease in royalty revenue is primarily due to lower net sales of $8.0 million for the three months ended September 30, 2015, compared to $10.8 million for the corresponding period in 2014. Current year first nine months revenues were $3.6 million, down from $44.9 million in the first nine months of 2014, reflecting royalty income of $3.2 million compared to $3.7 million and collaboration revenue of $0.4 million compared to $41.1 million in the corresponding period in 2014.

Third quarter research and development expenses were flat compared to the third quarter of 2014, reflecting higher expenses for the Azedra clinical trial, 1404 and consulting expenses, offset by lower contract manufacturing and compensation expenses. Year-to-date research and development expenses decreased by $2.1 million compared to the corresponding period in 2014 primarily due to lower clinical trial expenses for PSMA ADC and 1404 and compensation expenses, partially offset by higher Azedra-related expenses. Third quarter general and administrative expenses increased by $0.5 million from the corresponding period in 2014 primarily due to higher compensation, consulting and professional fees. Year-to-date general and administrative expenses increased by $2.9 million compared to prior year period primarily due to an action brought by a former employee. The change in the contingent consideration liability for the quarter and year-to-date periods is a non-cash item and resulted from changes in estimates for fair value of contingent consideration liability.

Third Quarter and Recent Events

In October, the Company announced an offer to acquire EXINI Diagnostics AB, a leader in the development of software solutions for medical decision support based on advanced image analysis. The Company reported today that over 90 percent of the outstanding shares of EXINI have been tendered, and Progenics expects the settlement of the Offer to occur on or about November 12, 2015. EXINI is expected to complement Progenics’s strategy to support its imaging and therapeutic agents with sophisticated software and other technologies that help physicians and patients visualize, understand, target and treat cancer. The planned acquisition would provide Progenics with in-house development capabilities in these areas that it can apply to its own pipeline, including its prostate cancer imaging agents 1404 and PyL.

Also in October, Dr. Thomas Strack joined Progenics as Vice President of Clinical Affairs. Prior to joining Progenics, he was the Vice President of Research and Development at Asubio Pharmaceuticals where he led clinical research programs as well as R&D portfolio strategies. Prior to joining Asubio, Dr. Strack held a number of key positions at Eli Lilly, Pfizer, and Takeda Pharmaceuticals, where he led global clinical programs in multiple therapeutic areas, including endocrinology, ophthalmology, and oncology. Dr. Strack is board certified in internal medicine and endocrinology.

In September, Valeant Pharmaceuticals International, Inc. and Progenics announced that the U.S. Food and Drug Administration (FDA) has accepted for review Valeant’s New Drug Application for RELISTOR (methylnaltrexone bromide) Tablets for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of April 19, 2016.

In August, Progenics announced an exclusive worldwide licensing agreement with Johns Hopkins University for [18F]DCFPyL ("PyL"), a clinical-stage prostate specific membrane antigen (PSMA)-targeted imaging agent for prostate cancer. PyL complements Progenics’ existing portfolio of pipeline products for the detection and treatment of prostate cancer, including 1404, the Company’s lead PSMA-targeted imaging agent that is used in conjunction with widely-available SPECT-CT imaging.

In July, Progenics announced that the FDA granted Azedra designation as a Breakthrough Therapy for the treatment of patients with iobenguane-avid metastatic or recurrent pheochromocytoma and paraganglioma. Azedra is currently being evaluated in a pivotal Phase 2b trial, which is being conducted under a Special Protocol Assessment Agreement (SPA), and has received Orphan Drug and Fast Track designations from the FDA.

Also in July, the Company announced the design and key elements of its planned Phase 3 clinical trial for 1404, following the successful completion of the End-of-Phase 2 interactions with the FDA. Progenics expects the Phase 3 trial to commence by the end of this year.

(Filing, 10-Q, Galectin Therapeutics, NOV 9, 2015, View Source [SID:1234508110])

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(Filing, 10-Q, ImmunoCellular Therapeutics, NOV 9, 2015, View Source [SID:1234508160])

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On November 09, 2015 NewLink Genetics Corporation (NASDAQ:NLNK), a biopharmaceutical company at the forefront of discovering, developing and commercializing novel immuno-oncology product candidates, including both cellular immunotherapy and checkpoint inhibitor platforms, to improve the lives of patients with cancer, reported that a study update from a Phase 1b/2 study of indoximod in combination with temozolomide in temozolomide-refractory glioblastoma patients will be presented at the 20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology on November 19-22, 2015 at the San Antonio Marriott Rivercenter (Press release, NewLink Genetics, NOV 9, 2015, View Source [SID:1234508119]).

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Details for the presentation follow:

Abstract Title: Updates on phase 1b/2 combination study of the IDO pathway inhibitor indoximod with temozolomide for adult patients with temozolomide-refractory primary malignant brain tumors
Abstract Number: IMCT-21
Time: 7:30-9:30 p.m.
Date: Friday, November 20
Location: Ballroom B
Session Type: Poster

On November 9, 2015 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported that two posters detailing preclinical data from its BTK and PDK1 inhibitor programs were presented on Sunday, November 8th 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) being held in Boston, Massachusetts (Press release, Sunesis, NOV 9, 2015, View Source;p=RssLanding&cat=news&id=2110307 [SID:1234508142]).

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The two poster presentations (Abstracts C198 and C186), titled "SNS-062 is a potent noncovalent BTK inhibitor with comparable activity against wild type BTK and BTK with an acquired resistance mutation" and "PDK1 inhibitors SNS-229 and SNS-510 cause pathway modulation, apoptosis and tumor regression in hematologic cancer models in addition to solid tumors," are available on the Sunesis website at www.sunesis.com.

"These data represent the first peer-reviewed presentations by Sunesis of our two proprietary kinase inhibitor pipeline programs," said Dan Swisher, Chief Executive Officer of Sunesis. "Each shows compelling, anti-cancer activity and a distinct product profile. SNS-062, our novel, second-generation BTK inhibitor, maintains potent preclinical activity in the presence of a cysteine-481 mutation associated with acquired resistance to ibrutinib. In addition, SNS-062 has a kinase selectivity profile distinct from ibrutinib that may confer additional safety and efficacy advantages that we look forward to uncovering in our upcoming clinical studies. SNS-510 and SNS-229, which belong to a novel class of PDK1 kinase inhibitors, show broad activity in a variety of hematologic cancer cell lines, including cell lines resistant to PI3K and AKT inhibitors, that correlates with significant PDK1 pathway modulation and anti-proliferative activity. We believe this program could soon yield a first-in-clinic selective PDK1 inhibitor to test this important pathway in cancer patients. Near term, we look forward to advancing SNS-062 into the clinic in the first quarter of 2016."

Study Results in Detail

"SNS-062 is a potent noncovalent BTK inhibitor with comparable activity against wild type BTK and BTK with an acquired resistance mutation"

For this study, Sunesis researchers explored the potential of SNS-062, a potent, noncovalent BTK inhibitor, to overcome resistance mechanisms of ibrutinib, a BTK inhibitor with validated anti-cancer efficacy in several B-cell malignancies. These resistance mechanisms include mutation of the cysteine in the BTK active site that ibrutinib requires for covalent binding (C481). SNS-062 has a kinase selectivity profile distinct from ibrutinib showing nM binding affinity for BTK, ITK and Tec kinase family members, but does not meaningfully bind EGFR. A lack of EGFR inhibition by SNS-062 may offer safety advantages over ibrutinib, including reduced diarrhea and rash potentially related to inhibition of EGFR.

Prolonged SNS-062 mediated in vivo inhibition of BTK correlates with potent anti-inflammatory activity in a BTK dependent B-cell mediated collagen induced rat arthritis model. To assess the activity of SNS-062 and ibrutinib against BTK with acquired resistance mutations, inhibition of wild type (WT) and mutant C481S BTK was evaluated in direct kinase assays. SNS-062 inhibits WT and C481S BTK with similar inhibitory concentrations while ibrutinib potency is reduced 40 fold. Similarly, ibrutinib shows a 100 fold loss of potency in inhibiting pBTK levels in C481S BTK expressing cells while SNS-062 activity is unaffected.

SNS-062 shows good oral bioavailability in multiple animal species with a terminal half-life of three to six hours. Pharmacokinetic, pharmacodynamic and toxicity studies demonstrate that SNS-062 plasma concentrations providing >90% inhibition of BTK can be sustained with acceptable tolerability.

"PDK1 inhibitors SNS-229 and SNS-510 cause pathway modulation, apoptosis and tumor regression in hematologic cancer models in addition to solid tumors"

Phosphatidylinositol (PI) dependent kinase 1, or PDK1, is a master kinase that activates kinases important in cell growth and survival including members of the AKT, PKC, RSK and SGK families and can interact with its substrates through PI-dependent (PH-mediated) or PI-independent (PIF-mediated) mechanisms. For this study, Sunesis researchers characterized two potent PDK1 kinase inhibitors, SNS-229 and SNS-510, with broad preclinical antitumor activity in hematologic cancers.

SNS-229 and SNS-510 belong to a novel class of PDK1 inhibitors that bind the inactive conformation of PDK1 as determined by X-ray crystallography and induce a conformational change that perturbs the PIF-pocket, thereby inhibiting PIF-mediated substrate binding, in contrast to the ATP-competitive PDK1 inhibitor tool compounds GSK2334470 and BX-320.

SNS-229 and SNS-510 were evaluated in more than twenty cell lines derived from hematologic cancers including acute myeloid leukemia, multiple myeloma, B-cell lymphoma, and mantle cell lymphoma. SNS-510 shows strong anti-proliferative activity and induces apoptosis in PI3K and AKT inhibitor resistant cell lines. SNS-229 and SNS-510 are compared to the PDK1 inhibitor GSK2334470 and were up to 30 fold more potent at inhibiting PDK1, S6K, RSK and AKT phosphorylation and up to 50 fold more potent in cancer cell viability assays.

In vivo, SNS-510 shows dose and time dependent inhibition of PDK1 autophosphorylation and up to 90% inhibition of RSK2 and AKT phosphorylation after eight hours, whereas GSK-2334470 and the pan-PI3K inhibitor GDC0941 only show moderate PDK1 and RSK2 inhibition and no AKT inhibition. In PK studies in CD/1 mice, SNS-229 and SNS-510 have good pharmacokinetic properties, with a terminal half-life of four to five hours and an oral bioavailability of >90%.

In an AML xenograft mouse model, both SNS-229 and SNS-510 show dose-related efficacy with >95% tumor growth inhibition and partial regression (>50% tumor shrinkage) in 70% and 100% of animals at the highest dose after 21-day dosing. These studies show that targeting the inactive conformation of PDK1 leads to potent and sustained pathway inhibition resulting in strong tumor growth inhibition and regression.