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Calithera Presents Preclinical Study Findings for CB-1158 at the 2015 AACR-NCI-EORTC International Conference

On November 06, 2015 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported it will announce preclinical data today for its lead immuno-oncology therapeutic candidate, CB-1158, at the 2015 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) in Boston, Massachusetts (Press release, Calithera Biosciences, NOV 6, 2015, View Source;p=RssLanding&cat=news&id=2107977 [SID:1234508339]). CB-1158 is a first-in-class immuno-oncology metabolic checkpoint inhibitor targeting arginase, a key immunosuppressive enzyme that limits T-cell proliferation in a wide range of tumors.

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"We believe that drugs targeting metabolic checkpoints have the potential to be transformational in the treatment of cancer. At Calithera, we are dedicated to researching and developing first-in-class therapies that could significantly advance the field of oncology. We have made significant progress on our CB-1158 program and remain on track to file an Investigational New Drug application (IND) in the first half of 2016," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.

Preclinical data will be presented in a poster titled, "CB-1158 Inhibits the Immuno-Oncology Target Arginase and Causes an Immune Mediated Anti-Tumor Response," (Abstract #A195). CB-1158, a highly selective, orally bioavailable, small molecule inhibitor of human arginase with nanomolar potency, demonstrated single agent efficacy in animal models. Inhibition of tumor growth was accompanied by a rapid increase in the local concentration of arginine, and the induction of multiple pro-inflammatory changes in the tumor microenvironment. CB-1158, when administered with anti-CTLA-4, increased CD8+ T-cell infiltrates in the tumor. The addition of CB-1158 to anti-CTLA-4 and anti-PD-1, significantly inhibited tumor growth in a mouse model that was resistant to dual checkpoint inhibitor therapy. CB-1158 was well tolerated as a single agent and in combination with checkpoint inhibitors in animal studies.

Arginase is a critical immunosuppressive enzyme responsible for T-cell suppression. Arginase depletes arginine, a nutrient that is critical for the activation, growth and survival of the body’s cancer-fighting immune cells, known as cytotoxic T-cells. Arginase inhibitors can restore arginine levels and reverse this immunosuppressive effect of myeloid-derived suppressor cells (MDSCs). Myeloid cells are present in many human tumors and are correlated with poor prognosis. CB-1158 has the potential for anti-tumor activity in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role.

8-K – Current report

On November 6, 2015 Lixte Biotechnology Holdings, Inc. (OTCQB: LIXT) reported that in an ongoing Phase I trial its lead anti-cancer compound, LB-100, was associated with stabilization of a variety of advanced cancers that had been progressing despite extensive prior treatment (Filing, 8-K, Lixte Biotechnology, NOV 6, 2015, View Source [SID:1234508181]). The results were presented at the AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference, Boston, on November 6. The authors were Vincent Chung, City of Hope, Duarte, CA; Donald Richards, Texas Oncology, Tyler, TX; Fadi Braiteh, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; John S. Kovach, Lixte Biotechnology Holdings, Inc., East Setauket, NY; Aaron Scott Mansfield, Mayo Clinic, Rochester, MN.

A total of 21 patients received LB-100 for 3-consecutive days in 3-week cycles. Nine of these patients had stabilization of their disease without significant toxicity. One patient with pancreatic cancer received 14 cycles of LB-100 (42 weeks); one with thymoma, 9 cycles; one with testicular and one with carcinoid of the lung, 5 cycles; two with ovarian, 3 and 6 cycles; and one with NSCLC and one with duodenal cancer, 3 cycles. The average number of cycles received at the last four evaluable dose levels of LB-100 was 4.8 (14.4 weeks). In a study by Mansfield et al (2015 JCO 33[15] suppl:2567), the average number of cycles of a new drug in 51 NCI-sponsored Phase 1 trials conducted from 1994-2014 involving 1841 patients was 2.0 (6-8 weeks).

John S. Kovach M.D., founder and president of Lixte, said "Lixte interprets the results as showing that LB-100 has single agent activity in suppressing the growth of several types of cancer. What is highly encouraging is that stabilization of disease occurred in the absence of dose-limiting toxicity. In fact, most patients tolerated repeated doses without any ill-effects. As pre-clinical studies have shown that LB-100 potentiates the effectiveness of cytotoxic agents, we believe that LB-100 alone and in combination with standard anti-cancer drugs and/or radiation may offer new therapeutic options for a spectrum of neoplastic diseases."

TESARO Announces Data Presentations for Niraparib at the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

On November 6, 2015 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported the presentation of three posters describing niraparib at the 2015 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), November 5-9, 2015, in Boston, Massachusetts (Press release, TESARO, NOV 6, 2015, View Source [SID:1234508096]). The posters describe the homologous recombination deficiency (HRD) analysis being performed on tumor samples from the ongoing Phase 3 NOVA trial of niraparib in patients with ovarian cancer, in addition to preclinical data demonstrating that niraparib crosses the blood brain barrier in animal models and highlighting potential genetic markers of resistance in animal models of small cell lung cancer.

"We are executing a very comprehensive development program for niraparib, and believe that the emerging profile of this promising candidate warrants expansion to a variety of tumor types, as a monotherapy and in combination with immuno-oncology and other targeted agents," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "We are very optimistic about the potential of niraparib for patients with ovarian, breast and other cancers, and we look forward to initiating several new trials in the coming months."

Presentation Details:

Sunday, November 8, 2015, 12:30 PM to 3:30 PM
Homologous recombination deficiency of high grade serous ovarian tumors from the NOVA Phase III clinical study
Abstract: C53, Location: Session C, Hall C-D

Saturday, November 7, 2015, 12:30 PM to 3:30 PM
The PARP inhibitor, niraparib, crosses the blood brain barrier in rodents and is efficacious in a BRCA2-mutant intracranial tumor model
Abstract: B168, Location: Session B, Hall C-D

Saturday, November 7, 2015, 12:30 PM to 3:30 PM
A mouse avatar tumor maintenance study identified a subset of SCLC patient-derived tumor xenograft models sensitive to the PARP inhibitor niraparib
Abstract: B169, Location: Session B, Hall C-D

About Niraparib

Niraparib is an orally active and potent poly (ADP-ribose) polymerase, or PARP, inhibitor. A Phase 1/2 monotherapy study of niraparib has been completed in more than 100 patients with advanced solid tumors. Two Phase 3 trials are currently ongoing to evaluate a single oral dose of niraparib for patients with ovarian cancer and for patients with BRCA-positive breast cancer.

Stemline Therapeutics Reports Third Quarter 2015 Financial Results

On November 6, 2015 Stemline Therapeutics, Inc. (Nasdaq:STML) reported financial results for the quarter ended September 30, 2015 (Press release, Stemline Therapeutics, NOV 6, 2015, View Source [SID:1234508095]).

Ivan Bergstein, M.D., Stemline’s Chief Executive Officer, commented, "During the third quarter, we made significant progress on many fronts as we continue to advance our clinical programs forward. We are actively enrolling patients, and opening additional sites, in the expansion stage of our ongoing SL-401 pivotal trial in blastic plasmacytoid dendritic cell neoplasm, BPDCN. We look forward to sharing clinical updates from both the lead-in and initial expansion stages of this trial at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) meeting this December, and on into next year."

Dr. Bergstein continued, "We remain focused on the BPDCN indication while continuing to pursue expansion opportunities for SL-401 in additional malignancies. We have single agent trials currently open in several indications and we anticipate combination studies coming on-line as well. We are also continuing to develop our other pipeline candidates, SL-701 and SL-801, and look forward to treating our first patient with SL-801, our novel XPO1 inhibitor, early next year. With a strong cash position and multiple ongoing programs advancing across a range of indications of unmet medical need, we remain focused on achieving our objective of building a leading commercial stage biopharmaceutical company."

Third Quarter 2015 Financial Results Review

Stemline ended the third quarter of 2015 with $104.0 million in cash, cash equivalents and investments, as compared to $58.6 million as of December 31, 2014. In the first quarter of 2015, the Company completed an equity offering raising $68.6 million in gross cash proceeds on the sale of 4.4 million common shares.

For the third quarter of 2015, Stemline had a net loss of $9.2 million, or $0.53 per share, compared with a net loss of $6.9 million, or $0.53 per share, for the same period in 2014.

Research and development expenses were $7.3 million for the third quarter of 2015, which reflects an increase of $2.3 million compared with $5.0 million for the third quarter of 2014. The higher expenses during the third quarter were primarily attributable to the ramp up of SL-401 and SL-701 clinical activities. Also, we incurred costs relating to SL-801 IND-enabling studies.

General and administrative expenses were $2.2 million for the third quarter of 2015, which reflects an increase of $0.2 million compared with $2.0 million for the third quarter of 2014. The higher costs were primarily attributable to an increase in non-cash stock based compensation expense relating to employees.

PharmaMar’s Novel Antibody-Drug Conjugate (ADC) demonstrates anticancer activity in HER2-expressing Tumors

On November 6, 2015 PharmaMar (MSE:PHM), a world-leading biopharmaceutical company in the discovery and development of innovative marine-derived anticancer drugs, reported that its novel Antibody-Drug Conjugate (ADC) demonstrates strong anticancer activity in vitro and in vivo against tumors expressing HER2 derived from breast, gastric and ovarian cancers (Press release, PharmaMar, NOV 6, 2015, View Source [SID:1234508082]).
The novel ADC MI130004 consists of a new marine-derived tubulin inhibitor (PM050489) that is covalently bound to the HER2 antibody trastuzumab via a nonhydrolysable linker. The results have been presented today in a poster presentation during the Therapeutic Agents – Biological session at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference "Molecular Targets and Cancer Therapeutics" taking place in Boston, November 5-9.

When tested in a panel of tumor cells expressing the receptor HER2 in their surface (HCC-194, SK-BR3 and BT-747) or tumor cells that do not express it (MCF-7 and MDA-MB-231), MI13004 demonstrated strong potency in those cells expressing the receptor. The authors found that the ADC MI130004 impairs tubulin polymerization, causing disorganization of the microtubule network leading to mitotic failures and halting cell division in cells expressing HER2, similar to the effect of the payload PM50489.

In the study, HER2-expresing tumor cells from breast, gastric and ovarian cancers were subcutaneously implanted into immunosuppressed mice to develop tumors up to certain volume (about 114 mm3). Upon treatment with MI130004 at different
doses once a week over a course of 5 weeks, mice treated with the highest dose showed substantial tumor shrinkage with complete tumor remissions in all the mice implanted with BT747 breast tumor cells that lasted up to 120 days. MI130004 was
shown to induce complete remissions in some of, but not all, the mice implanted with the breast tumor cells JIMT-1, the two gastric cancer cells Gastric-008 and N87 and the two ovarian cancer cells SK-OV-3 and A2780cis. Complete tumor remissions lasted even 385, 354 and 341 days in mice implanted with SK-OV-3, Gastric-008 and A2780cis, respectively.

The effect of MI130004 in all HER2-expressing tumors was confirmed 24h after treatment by showing mitotic aberrations in tumor cells indicating an anticancer activity mediated by microtubule inhibition and blockade of cell division.

Title: MI130004, a new ADC with a payload of marine origin shows outstanding activity against HER2-expressing tumors (Abstract A147). Session Start/End Time and location: Friday, Nov 06, 12:15 PM – 3:15 PM, session A, Hall C-D.