On April 19, 2018 Oasmia reported that the Private Placement has enabled Oasmia to place 26 new convertible instruments with a limited group of investors at a nominal value of SEK 1,000,000 per convertible instrument through an accelerated book building procedure (Press release, Oasmia, APR 19, 2018, View Source [SID1234556570]).

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The convertible loan is issued with the purpose of replacing the Company’s financing under the Company’s convertible loan 2017:2 in the total amount of MSEK 26, which fell due for payment 18 April 2018. The fallen due loan amount under the Company’s convertible loan 2017:2 will be paid to the convertible loan holders in May 2018 and the fallen due interest was paid in April 2018.

In order to enable the placement, the Board of Directors of Oasmia has, by virtue of the authorisation granted by the Annual General Meeting held on 25 September, 2017, resolved on a directed issue of a new convertible loan in the amount of SEK 26,000,000. The convertible instruments have been subscribed at 100 per cent of the nominal amount and the convertible loan bear an interest rate of 8 per cent per year. The conversion rate is based on the closing price of Oasmia’s shares on Nasdaq Stockholm on 18 April 2018 with premium and will amount to SEK 4.90. The term of the loan is approximately one year with a maturity date on 22 April 2019 if not converted to shares earlier. The terms of the convertible instruments are based on an accelerated book building procedure on 18 April 2018 and the Board of Directors has thereby ensured that the terms of the convertible instruments corresponds to fair market standards.

If the convertible loan is fully converted into shares, the number of shares in Oasmia increases by 5,306,122 from 176,406,372 to 181,712,494 and the share capital increases by SEK 530,612.20 from SEK 17,640,637.20 to SEK 18,171,249.40. In the event of a full conversion into shares, the dilution effect will amount to approximately 2.9 per cent.

On April 18, 2018 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage biopharmaceutical company focused on discovering and developing novel anti-cancer therapeutics, presented preclinical data during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting related to two of its therapeutic candidates, anti-TIGIT (OMP-313M32), currently in the Phase 1a portion of a Phase 1a/b study, and GITRL-Fc trimer (OMP-336B11), currently in a Phase 1a study (Press release, OncoMed, APR 18, 2018, View Source [SID1234525498]). In addition, preclinical data was presented exploring the ability of OncoMed’s Wnt antagonist vantictumab (anti-FZD, OMP-18R5) to potentiate immune responses to checkpoint agents.

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TIGIT (T-cell immunoreceptor with Ig and ITIM domains) is an inhibitory checkpoint receptor that binds to PVR ligand, a protein broadly expressed on tumor cells and tumor-infiltrating cells, and, in doing so, blocks T-cell activation. OncoMed’s presentation (Abstract 5627) showed that anti-TIGIT treatment reduced the abundance of regulatory T-cells (Tregs) within tumors in animal models, and mechanistic studies demonstrated an important contribution of effector function for anti-tumor efficacy. "These investigations highlight the potential of our anti-TIGIT antibody," said Ann Kapoun, Ph.D., OncoMed’s Vice President of Translational Medicine. "These translational research efforts inform our biomarker strategies and may help us identify patients whose tumors are most likely to benefit from our therapeutic candidates."

A series of preclinical studies (Abstract 70, Abstract 2726, Abstract 3826) from OncoMed highlighted the ability of GITRL-Fc, a novel linkerless ligand trimer that binds to the co-stimulatory receptor GITR (glucocorticoid-induced TNF receptor family-related protein), to function as a robust GITR agonist by both stimulating T-cell and NK responses and reducing the abundance of Tregs in tumors. The studies also investigated the impact of aging on anti-tumor immune response, an important and often underappreciated parameter impacting the efficacy of immuno-oncology strategies.

Another preclinical study (Abstract 1733) examined the synergistic impact of OncoMed’s Wnt pathway antagonist vantictumab on the ability of checkpoint agents to promote an effective anti-tumor immune response. These data add to a growing recognition of the importance of the Wnt pathway in shaping immune function.

"The data detailed in these AACR (Free AACR Whitepaper) presentations exemplify the ongoing extensive efforts to deepen our understanding of the mechanisms of action of our agents" said Austin Gurney Ph.D., OncoMed’s Senior Vice President of Research and Chief Scientific Officer. "With both our anti-TIGIT and GITRL-Fc programs advancing in Phase 1 studies, these research efforts will have direct impact on informing our clinical programs."

Below are additional highlights from the OncoMed poster presentations:

Abstract 5627 – Anti-TIGIT biomarker study: Inhibition of TIGIT induces loss of Tregs from tumors and requires effector function for tumor growth inhibition

Using a surrogate anti-TIGIT antibody, potent single-agent dose-dependent anti-tumor efficacy was demonstrated on large established CT26 WT tumors. Anti-TIGIT efficacy was shown to require effector function for tumor growth inhibition and biomarker analysis demonstrated reduction of Treg frequency and activation of T-cells and NK cells as part of the mechanism of action of anti-TIGIT. CD226, a co-receptor for TIGIT’s ligands PVR and PVRL2, was significantly upregulated in T-cells, Tregs and NK cells, reflecting a feedback loop activated by the inhibition of TIGIT activity. Anti-TIGIT gene signatures in tumors and in blood were identified from multiple syngeneic models and may be potential biomarkers for measuring anti-TIGIT activity. Additionally in a human tissue study, TIGIT expression on Tregs was found to be considerably higher than on CD8+ T-cells in multiplexed IHC panels across a panel of multiple solid tumors types.

Abstract #70 – Effect of aging on the antitumor activity of GITRL-Fc

It is now appreciated that the immune system changes in response to aging. In this study, the activity of GITRL-Fc protein was compared in both young and older mice. Compared to young mice, tumors grew faster in older mice. This may be due in part to an observed greater prevalence of myeloid-derived suppressor cells (MDSC) in older mice. GITRL-Fc significantly inhibited tumor growth in both older and younger mice with efficacy more pronounced in young mice. In older mice, GITRL-Fc (mIgG2a) was still able to deplete Tregs in tumor and increase Tregs in the spleen as has been previously shown with GITRL-Fc in young mice. A GITRL-Fc protein deficient in effector function (mIgG2a (N297A)) did not deplete Tregs in the tumor but did retain anti-tumor growth activity. Collectively, these data demonstrate that Treg depletion and activation of GITR signaling contribute to the anti-tumor efficacy of GITRL-Fc in older mice.

Abstract #2726 – In vitro functional activity of OMP-336B11, a GITRL-Fc fusion protein, on primary human immune cells

In this study, functional characterization of OMP-336B11 in various human immune cell assays was presented. OMP-336B11 enhanced activated human T-cell proliferation and augmented IL-2 induced IFNγ from human NK cells. Notably, OMP-336B11 demonstrated superior activity compared to agonist anti-GITR antibodies. OMP-336B11 is designed with an IgG1 Fc domain in order to elicit NK-mediated cytotoxicity of high GITR-expressing cells (i.e., Tregs). Co-incubation of primary human NK cells (effector) and GITR expressing cells (target) resulted in an OMP-336B11 dependent dose-titratable increase in target cytotoxicity.

Abstract #3826 – GITRL-Fc biomarker and mechanism study: GITRL-Fc reduces Treg frequency in tumors and requires effector function for inhibition of tumor growth

Using a surrogate GITRL-Fc molecule, potent single agent dose-dependent anti-tumor efficacy was demonstrated on large established CT26.WT tumors. Biomarker analysis showed that loss of Tregs, activation of T-cells and Fc-mediated effector function are key elements in the mechanism of action of the molecule. Immuno-phenotyping of tumor-associated immune cells revealed a reduction in Treg frequency in the tumor by 24 hours post-dose that was maintained at 7 and 14 days. GITRL-Fc treatment increased proliferation and activation markers on tumor-associated CD4+ and CD8+ T-cells, suggesting an increased cytotoxic environment within the tumor. GITRL-Fc gene signatures were identified in tumors and blood from multiple syngeneic models and may be used as potential biomarkers along with multiplexed IHC panels (e.g. GITR+CD4+ T-cells, GITR+CD8+ T-cells) that were developed. Additional studies comparing intratumoral (IT) vs intraperitoneal GITRL-Fc injection demonstrated both routes of administration produced similar efficacy, suggesting IT administration may be an alternative route of administration.

Abstract #1733 – Wnt antagonists synergize with immune checkpoint inhibitors to enhance anti-tumor responses

While enhanced Wnt signaling has been shown to play a major role in cancer stem cell biology, more recent studies have implicated Wnt in the development of resistance to anti-tumor immune responses. In murine tumor models, targeting Wnt signaling using the Fzd receptor monoclonal antagonist antibody vantictumab in combination with immune checkpoint inhibitors anti-CTLA-4 or anti-PD1 induces enhanced anti-tumor responses leading to decreased tumor volume and increased infiltration of activated CD8+ T-cells into the tumor microenvironment. In addition, the data showed that combined Wnt and immune checkpoint inhibition decreased Tregs and immune suppressive myeloid cell populations, enhanced cytotoxic T-cell activity and increased antigen presentation by APCs. These results suggest that co-targeting Wnt and immune checkpoint proteins may provide valuable opportunities for novel combination strategies for immunotherapeutic clinical development.

These posters are available on the Pipeline section of OncoMed’s website, www.oncomed.com.

Additional information on the meeting can be found on the AACR (Free AACR Whitepaper) website www.aacr.org.

On April 18, 2018 Provectus Biopharmaceuticals, Inc. (OTCQB: PVCT, www.provectusbio.com), ("Provectus" or the "Company"), a clinical-stage biotechnology company developing PV-10 as the first small molecule oncolytic immunotherapy for solid tumor cancers, reported that the Japan Patent Office (JPO) had granted and the European Patent Office (EPO) had allowed the Company’s patent application for the combination of PV-10 with systemic immunomodulatory therapy (i.e., immune checkpoint inhibition) (Press release, Provectus Biopharmaceuticals, APR 18, 2018, View Source [SID1234525516]).Pfizer, Inc. is a co-assignee on the award and allowance.

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The JPO patent and EPO patent allowance are related to U.S. patent (USP) 9,839,688, "Combination of rose bengal and systemic immunomodulative therapies for enhanced treatment of cancer," which was awarded by the United States Patent and Trademark Office (USPTO) in December 2017. USP 9,839,688 is one of the continuations of the Company’s foundational cancer combination therapy patent, USP 9,107,887, which was awarded by the USPTO in August 2015.

Provectus’ patent portfolio provides global intellectual property protection into the 2030s for the synthesis and use of PV-10 and other halogenated xanthene-based therapeutics as monotherapies and part of combination therapies for cancer.

About PV-10

Provectus’ lead investigational cancer drug product, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. It elicits tumor immunity via activation of dendritic cells mediated by the release of damage-associated molecular pattern molecules. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers.

On April 18, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that its Management Board, with the approval of the Supervisory Board, has resolved to increase the share capital of MorphoSys AG by issuing 2,075,000 new ordinary shares from the authorized capital 2017-II, excluding pre-emptive rights of existing shareholders, to implement the initial public offering in the United States of 8,300,000 American Depositary Shares ("ADSs") pursuant to a Registration Statement on Form F-1, as amended, filed with the U.S. Securities and Exchange Commission (Press release, MorphoSys, APR 18, 2018, View Source [SID1234556336]). Furthermore, MorphoSys has granted the underwriters a 30-day option to purchase additional ADSs of up to 15% of the total number of ADSs placed in the offering (i.e. 1,245,000 additional ADSs). Each ADS will represent 1/4 of a MorphoSys ordinary share. The new ordinary shares underlying the ADSs represent 8.1% (including the underwriters’ option to purchase additional ADSs) of the registered share capital of MorphoSys prior to the consummation of the capital increase.

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Pricing of the offering is expected to occur on April 18, 2018, following the end of the bookbuilding in the United States.
Within the United States of America, the securities referred to in this release are offered only by means of a prospectus. A copy of the prospectus can be obtained from Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 1-212-902-9316 or by e-mailing [email protected]; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, telephone: 1-866-803-9204; Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525, ext. 6132, or by e-mailing [email protected].

A registration statement relating to these securities has been filed with the Securities and Exchange Commission but has not yet become effective. These securities may not be sold nor may offers to buy be accepted prior to the time the registration statement becomes effective.

On April 18, 2019 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to CB-839 in combination with cabozantinib for the treatment of patients with metastatic renal cell carcinoma who have received one or two prior lines of therapy, including at least one vascular endothelial growth factor tyrosine kinase inhibitor or the combination of nivolumab and ipilimumab (Press release, Calithera Biosciences, APR 18, 2018, View Source [SID1234535241]). CB-839 is a first-in-class, oral, selective, potent inhibitor of glutaminase being evaluated in the CANTATA trial. The trial is a randomized double-blind clinical study of cabozantinib in combination with CB-839 or placebo in 298 patients with clear cell renal cell carcinoma. The primary endpoint is progression free survival and the global study is open for enrollment.

"Despite a number of new therapies for the treatment of renal cell carcinoma, there remains a significant unmet need among advanced patients who have received prior treatment," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We are pleased that CB-839 has been granted Fast Track designation, demonstrating the FDA’s commitment to facilitate the development and expedite the review of our glutaminase inhibitor as an important new therapy for patients with advanced or metastatic renal cell carcinoma who have failed prior systemic therapy."

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The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of drugs and biologics, to treat serious or life threatening conditions, and to fill an unmet medical need. Specifically, Fast Track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support approval, and also provides the opportunity to submit sections of an NDA on a rolling basis as data become available. About CB-839 Calithera’s lead product candidate, CB-839, is a potent, selective, reversible and orally bioavailable inhibitor of glutaminase. CB-839’s onco-metabolism activity takes advantage of the unique metabolic requirements of tumor cells and cancer-fighting immune cells such as cytotoxic T-cells. It is currently being evaluated in Phase 2 clinical trials in multiple tumor types, in combination with standard of care agents.