On March 30, 2016 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) reported financial results for 2015 (Press release, ImmunoCellular Therapeutics, MAR 30, 2016, View Source [SID:1234510218]).

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Andrew Gengos, ImmunoCellular Chief Executive Officer, commented: "We made important progress in advancing the company in 2015. In particular, we designed and began executing what we believe is the best possible phase 3 registration trial for ICT-107 in patients with newly diagnosed glioblastoma. We took full advantage of about five years of placebo-controlled survival data and immune monitoring results from the phase 2 trial, conversations with key opinion leaders in the field of glioblastoma and discussions with major regulatory bodies in designing this trial. The process of bringing clinical sites online and screening patients in the US is accelerating, and we anticipate that all sites in the US, Canada and Europe will be activated by the end of 2016. In addition, our research relationships and collaborations with prestigious academic institutions, including the University of Texas MD Anderson Cancer Center, Stanford University and the University of Maryland, are progressing well, and represent value-enhancing opportunities for our Company. We are proud of the progress we made in 2015, and are looking forward to delivering another year of growth and achievement in 2016."

For the year ended December 31, 2015, ImmunoCellular incurred a net loss of $12.8 million, or $0.15 per basic and diluted share, compared to a net loss of $9.4 million, or $0.16 per basic and diluted share, for the year ended December 31, 2014. During 2015 the Company incurred $10.9 million of research and development expenses compared to $6.0 million in 2014. The $4.9 million increase primarily reflects the additional expenses associated with the phase 3 trial of ICT-107. General and administrative expenses increased in 2015 to $4.6 million from $3.9 million in 2014, primarily due to additional professional fees and payroll-related expenses. During 2015, the Company recorded a credit to other income of $2.9 million to reflect a write-down in the Company’s warrant liability compared to a credit to other income of $530,000 in 2014. For the quarter ended December 31, 2015, the Company recorded a net loss of $4.8 million, or $0.05 per basic and diluted share, compared to $2.1 million, or $0.03 per basic and diluted share, during the same period in 2014. The increase in the net loss between periods reflects the additional costs of the phase 3 trial of ICT-107.

The Company also reported that cash used in operations in 2015 was $19.0 million compared to $9.9 million in 2014. In addition to the incremental expenses associated with starting the phase 3 trial of ICT-107, the Company also purchased $2.2 million in supplies and made additional vendor deposits of $3.7 million related to the trial. These items will benefit future periods and are reflected on the Company’s balance sheet at December 31, 2015.

During 2015, the Company raised $14.6 million net of offering costs from the issuance of 26,650,000 shares of common stock and warrants to purchase 18,655,000 shares. The warrants have a term of five years and an exercise price of $0.66. During the third quarter of 2015, the Company was awarded $19.9 million from the California Institute of Regenerative Medicine (CIRM) that the Company will be entitled to receive as patients are enrolled in the phase 3 trial of ICT-107, and during the fourth quarter of 2015, the Company received $4.0 million in its first award payment from CIRM. The next award payment is anticipated to be $3.0 million when the next enrollment milestone is achieved. As of December 31, 2015, the Company had $22.6 million in cash.

The Company has agreed in principle with the staff of the SEC on a proposed settlement framework to an investigation related principally to its former Chief Executive Officer involving conduct between November 2011 and August 2012. If the settlement is approved, the Company would consent to the entry of an administrative order requiring that we cease and desist from any future violations of Sections 5, 17(a), and 17(b) of the Securities Act of 1933, as amended, and Section 10(b) of the Securities Exchange Act of 1934, as amended, without admitting or denying any allegations. The proposed settlement also involves the adoption of certain corporate governance amendments to the Company’s policies and practices, in particular as it relates to the retention of investor relations and public relations firms. The proposed settlement is contingent upon execution of a formal offer of settlement and approval by the Commissioners of the SEC, neither of which can be assured. Based upon the settlement framework with the staff of the SEC, the Company has not accrued and does not currently expect to accrue a liability related to this matter. However, any final settlement must be approved by the Commissioners. If the Commissioners do not approve the settlement, the Company may need to enter into further discussions with the SEC to resolve the investigated matters on different terms and conditions. As a result, there can be no assurance as to the final terms of any settlement including its financial impact or any future adjustment to the financial statements.

The ASK1-JNK3 signaling pathway plays a pivotal role in the pathogenesis of Parkinson’s disease (PD). The specific binding of β-arrestin2 to JNK3 is essential for activation of the ASK1-JNK3 cascade, representing a potential therapeutic target for preventing dopaminergic neuronal death in PD. The aim of this study was to identify a novel strategy for the prevention of dopaminergic neuronal death in PD.
Based on the specific binding of β-arrestin2 to JNK3, a 21-amino-acid fusion peptide, termed JNK3-N-Tat, was synthesized. We evaluated the ability of this peptide to inhibit the binding of β-arrestin2 to its target domain in JNK3 in vitro and in vivo.
The JNK3-N-Tat peptide inhibited activation of the ASK1-JNK3 cascade by disrupting the interaction between β-arrestin2 and JNK3. JNK3-N-Tat exerted beneficial effects through pathways downstream of JNK3 and improved mitochondrial function, resulting in attenuated MPP+/MPTP-induced damage. JNK3-N-Tat protected mesencephalic dopaminergic neurons against MPTP-induced toxicity.
JNK3-N-Tat, a JNK3-inhibitory peptide, protects dopaminergic neurons against MPP+/MPTP-induced injury by inhibiting the ASK1-JNK3 signaling pathway.

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Histone H1, referred to as the linker histone, associates with the nucleosome core particle. While there is indication that the budding yeast version of histone H1 (Hho1) contributes to regulation of chromatin structure and certain chromatin-related processes, such as DNA double-strand break repair, cells lacking Hho1 are healthy and display subtle phenotypes. A recent report has revealed that Hho1 is required for optimal sporulation. The studies described here were conducted to determine whether Hho1 influences meiotic recombination, an event that occurs during sporulation, involves generation and repair of DNA double-strand breaks, and is critical for spore viability.
Through tetrad analysis, cells with or without Hho1 were compared for meiotic reciprocal recombination events within several chromosome XV intervals. Parameters investigated included crossover frequency (genetic map distance) and crossover interference. No significant differences were detected between the two cell types. In agreement with earlier studies, spore viability was not affected by Hho1 absence.
These data suggest that complete absence of Hho1 from chromatin does not affect reciprocal recombination between homologous chromosomes during meiosis. Therefore, the basal level of Hho1 that remains after its reported depletion early in meiosis is unlikely to be important for regulating recombination. Furthermore, the subsequent accumulation of Hho1 as the haploid products mature does not appear to be crucial for spore viability.

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This randomized, double-blind trial compared proposed biosimilar LA-EP2006 with reference pegfilgrastim in women receiving chemotherapy for breast cancer (PROTECT-1).
Women (≥18 years) were randomized to receive LA-EP2006 (n = 159) or reference (n = 157) pegfilgrastim (Neulasta(), Amgen) for ≤6 cycles of (neo)-adjuvant TAC chemotherapy. Primary end point was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with absolute neutrophil count <0.5 × 10(9)/l) with equivalence confirmed if 90% and 95% CIs were within a ±1 day margin.
For DSN, LA-EP2006 was equivalent to reference (difference: 0.07 days; 90% CI: -0.09-0.23; 95% CI: -0.12-0.26).
LA-EP2006 and reference pegfilgrastim showed no clinically meaningful differences regarding efficacy and safety in breast cancer patients receiving chemotherapy.

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Death-associated protein kinase (DAPK3) is a serine/threonine kinase involved in various signaling pathways important to tissue homeostasis and mammalian biology. Considered to be a putative tumor suppressor, the molecular mechanism by which DAPK3 exerts its suppressive function is not fully understood and the field lacks an appropriate mouse model. To address these gaps, an in vitro three-dimensional tumorigenesis model was used and a constitutive DAPK3-knockout mouse was generated. In the 3D morphogenesis model, loss of DAPK3 through lentiviral-mediated knockdown enlarged acinar size by accelerated acini proliferation and apoptosis while maintaining acini polarity. Depletion of DAPK3 enhanced growth factor-dependent mTOR activation and, furthermore, enlarged DAPK3 acini structures were uniquely sensitive to low doses of rapamycin. Simultaneous knockdown of RAPTOR, a key mTORC1 component, reversed the augmented acinar size in DAPK3-depleted structures indicating an epistatic interaction. Using a validated gene trap strategy to generate a constitutive DAPK3-knockout mouse, it was demonstrated that DAPK3 is vital for early mouse development. The Dapk3 promoter exhibits spatiotemporal activity in developing mice and is actively expressed in normal breast epithelia of adult mice. Importantly, reduction of DAPK3 expression correlates with the development of ductal carcinoma in situ (DCIS) and more aggressive breast cancer as observed in the Oncomine database of clinical breast cancer specimens.
Novel cellular and mouse modeling studies of DAPK3 shed light on its tumor-suppressive mechanisms and provide direct evidence that DAPK3 has relevance in early development.
©2014 American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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