(Filing, 10-Q, BioMarin, AUG 5, 2015, View Source [SID:1234507022])

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On August 05, 2015 ArQule, Inc. (Nasdaq:ARQL) reported its financial results for the second quarter of 2015 (Press release, ArQule, AUG 5, 2015, View Source [SID:1234507015]).

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For the quarter ended June 30, 2015, the Company reported a net loss of $4,017,000 or $0.06 per share, compared to a net loss of $6,339,000 or $0.10 per share, for the second quarter of 2014. For the six-month period ended June 30, 2015, the Company reported a net loss of $8,568,000 or $0.14 per share, compared to a net loss of $13,480,000 or $0.22 per share for the six-month period ended June 30, 2014.

At June 30, 2015, the Company had a total of $48,001,000 in cash, equivalents and marketable securities.

Key Highlights

Phase 3 METIV-HCC trial for tivantinib progressing as expected: Enrollment in the pivotal Phase 3 trial for tivantinib in hepatocellular carcinoma (HCC) continues on track to complete patient accrual by year end. The trial targets a biomarker-defined patient population, is randomized 2:1 and will enroll approximately 300 patients with the primary end-point of overall survival.

Phase 2 trial for ARQ 087 in intrahepatic cholangiocarcinoma (iCCA) begins enrollment: The Phase 2 trial in iCCA with ARQ 087 follows the observation of two confirmed partial responses in this patient population in the Phase 1 portion of the program. ARQ 087 is a small molecule, multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family. The FGFR2 gene fusion is a pre-defined biomarker being used to enroll patients in the trial.

Positive feedback from the FDA on the Phase 1 trial for ARQ 092 in Proteus syndrome: Our collaborators at the National Institute of Health (NIH) received positive feedback from the FDA on the design of the Phase 1 trial for Proteus syndrome, and we expect the IND to be filed imminently. ARQ 092 is a small molecule designed to inhibit the AKT serine/threonine kinase. Proteus syndrome is a rare disease driven by the AKT1 mutation.

Increasing signs of efficacy in our Phase 1b trial for ARQ 092 in oncology: A Phase 1b trial is on-going in lymphoma, endometrial and other cancers harboring the AKT1 mutation. ARQ 092 continues to produce single agent responses, most recently in a breast cancer patient harboring the AKT1 mutation.

"We continue to be pleased with the robust rate of enrollment in the METIV-HCC trial with tivantinib as second-line therapy in MET-high HCC patients," said Paolo Pucci, chief executive officer of ArQule. "In addition, recent data from an investigator-initiated, Phase 2 study of tivantinib in combination with cetuximab in MET-high, KRAS wild-type metastatic colorectal cancer presented by Dr. Lorenza Rimassa at the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer further underscores the therapeutic activity of tivantinib in the MET-high patient population."

"ArQule’s proprietary pipeline continues to mature," said Dr. Brian Schwartz, head of research and development. "Our AKT inhibitor, ARQ 092, is on track to enroll its first patient in the third quarter in the Phase 1 trial in Proteus syndrome, a rare disease that is caused by a mutation in the AKT1 gene. Moreover, in the oncology portion of the ARQ 092 clinical program we have observed five patients with confirmed partial responses, four of which came in the Phase 1b enriched cohort and two of which had the same AKT1 mutation which occurs in Proteus syndrome. This is an evolving story that we continue to pursue."

"In all of our studies, with tivantinib, ARQ 087 and ARQ 092, our strategy of conducting biomarker driven clinical trials with small molecules in areas of high unmet need demonstrates our leadership in precision medicine and more importantly our commitment to deliver therapies for our patients on an expedited basis," said Mr. Pucci.

Revenues and Expenses

The Company reported research and development revenue of $3,004,000 for the quarter ended June 30, 2015, compared with $2,901,000 for the quarter ended June 30, 2014. For the six-month period ended June 30, 2015, research and development revenue for the company was $5,789,000, compared with $5,577,000 for the six-month period ended June 30, 2014.

Research and development revenue in the three and six months ended June 30, 2015 is comprised of revenue from the Daiichi Sankyo tivantinib development agreement and the Kyowa Hakko Kirin exclusive license agreement for tivantinib. The revenue increase in the three and six month periods is due to higher revenue from our Daiichi Sankyo tivantinib program.

Total costs and expenses for the quarter ended June 30, 2015 were $7,103,000 compared to $9,307,000 for the second quarter of 2014. For the six-month period ended June 30, 2015, total costs and expenses were $14,703,000 compared with $19,288,000 for the six-month period ended June 30, 2014.

Research and development costs for the three and six months ended June 30, 2015 were $4,327,000 and $8,740,000 respectively, compared with $6,236,000 and $12,967,000 for three and six-month periods of 2014.

Research and development expense in the quarter ended June 30, 2015 decreased by $1.9 million primarily due to lower labor related costs of $0.8 million related to the August 2014 restructuring, outsourced clinical and product development costs of $0.4 million, lab expenses of $0.3 million, and facility costs of $0.3 million.

Research and development expense in the six months ended June 30, 2015 decreased by $4.3 million primarily due to lower labor related costs of $1.7 million related to the August 2014 restructuring, outsourced clinical and product development costs of $1.1 million, lab expenses of $0.6 million, facility costs of $0.5 million and other costs of $0.3 million.

General and administrative expense for three and six-month periods ended June 30, 2015 were $2,776,000 and $5,963,000 respectively, compared to $3,071,000 and $6,321,000 for the three and six-month periods of 2014. General and administrative expense decreased in the three and six months ended June 30, 2015 principally due to lower non-cash stock compensation cost.

On August 5, 2015 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company focused on the discovery, development, and commercialization of targeted cancer therapies, reported financial results for the second quarter 2015 ended June 30, 2015 and provided an update on its pipeline (Press release, Loxo Oncology, AUG 5, 2015, View Source [SID:1234507019]).

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"Over the last several months, Loxo has delivered important advances against our pipeline priorities," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "Last week, we achieved an important milestone with the peer-reviewed publication of the first clinical response to LOXO-101, our tropomyosin receptor kinase (TRK) inhibitor. This important early result validates the potential of Loxo’s drug development approach – that selective, purpose-built medicines in genetically well-defined populations can show dramatic and early evidence that justifies continued and rapid drug development. Today we are excited to announce plans for a Phase 2 trial for this program, which accelerate development timelines ahead of previous plans. In addition, we have made significant progress with our preclinical pipeline, allowing us to prioritize our Rearranged during Transfection (RET) and our isoform-sparing Fibroblast Growth Factor Receptor (FGFR) programs, positioning them as our likely next IND filings."

Program Updates

Loxo provided the following updates on its development programs:

LOXO-101: the only potent, oral, selective inhibitor of the TRK family of proteins

Clinical Validation for LOXO-101 Published in Cancer Discovery

The research brief published on July 27, 2015 in Cancer Discovery provides early clinical validation of LOXO-101 against TRK fusion cancer.

The publication, authored in collaboration with Foundation Medicine, Inc. and the Doebele Research Lab at the University of Colorado, includes the case study of the first TRK fusion patient treated in the Phase 1 trial of LOXO-101. A woman with advanced soft tissue sarcoma widely metastatic to the lungs enrolled on study and experienced substantial tumor regression, with imaging studies after one month demonstrating a partial response (PR) as defined by standard RECIST 1.1 criteria. The patient’s shortness of breath rapidly resolved and she was able to discontinue her supplemental oxygen and resume activities of daily living. As discussed in the publication, with four months of treatment, additional CT scans demonstrated almost complete tumor disappearance of the largest tumors. After four months of dosing, the patient did not have any adverse events that were attributed to LOXO-101.

The publication also describes novel assays for assessing LOXO-101’s impact on TRK signaling, patient-derived TRK fusion models in vitro and in vivo which illustrate LOXO-101’s TRK inhibition, and the first-ever description of the molecular epidemiology of TRK fusions in soft tissue sarcoma.

LOXO-101 Phase 2 Trial to Open in the Second Half of 2015

Based on evidence from the Phase 1 trial, including drug exposures that exceeded expectations, Loxo plans to initiate a Phase 2 trial in the second half of this year, earlier than previously anticipated. The trial will be a multicenter, international Phase 2 open label study in adult cancer patients whose tumors harbor TRK fusions. Loxo will provide additional details on the timing, size, and design of the Phase 2 trial after the first clinical site is open.
Loxo believes that a wide variety of tumor types harbor TRK fusions, and plans to work creatively with clinical partners to identify patients with these genetic alterations. Loxo will provide additional details on these plans after the first clinical site of the Phase 2 trial is open.

LOXO-101 Phase 1 Update

In the ongoing Phase 1 study, LOXO-101 continues to consistently achieve systemic drug exposures anticipated to inhibit TRK signaling by over 90%.
Loxo anticipates presenting additional data from the Phase 1 study at a leading medical meeting likely by the first half of 2016.
An update on the future direction of the ongoing Phase 1 trial will be provided in conjunction with the start of the Phase 2 trial.

Pre-clinical Programs

Prioritization of RET and FGFR Programs

Loxo’s collaboration with Array BioPharma continues to generate compelling and differentiated chemical matter. Loxo has used its multi-target, prioritize-by-success collaboration structure to focus on RET and FGFR.
Activating fusions and mutations in RET have been identified across a range of cancer histologies. Loxo is designing a highly specific RET inhibitor that optimizes on-target potency for RET fusions, activating mutations, and anticipated resistance mutations.
Activating fusions and mutations in FGFR3 and FGFR2 have also been identified across a range of cancer histologies. However, most small molecule FGFR inhibitors are functionally equipotent against isoforms FGFR1, FGFR2 and FGFR3, and are associated with metabolic and systemic toxicities that limit dose, duration of therapy and target engagement. Loxo is designing an FGFR1-sparing inhibitor that has the potential to avoid many of the side effects that have been endemic to the FGFR class.
Consistent with prior guidance, Loxo has submitted preclinical data abstracts for presentation 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) meeting in November 2015 in Boston, MA. These data will provide evidence of some of the clinically-differentiating features of these programs. Loxo will provide IND guidance for one of these programs by the end of 2015.

Loxo has elected not to file an IND in the first half of 2016 on either of the two unnamed preclinical programs discussed in previous announcements. These programs have identified lead candidates, but still require additional target validation to merit clinical investigation, in the opinion of the Loxo scientific advisory board and management.

Second Quarter 2015 Financial Results

As of June 30, 2015 Loxo had aggregate cash, cash equivalents and investments of $101.8 million, compared to $112.9 million as of December 31, 2014.

The Company continues to expect cash burn of $30-$33 million in 2015, and based on the current operating plan, the Company believes existing capital resources will be sufficient to fund anticipated operations into 2017.

Research and development expenses were $5.7 million for the second quarter 2015 compared to $2.7 million for the second quarter 2014. The increase was primarily due to expanded clinical development activities for LOXO-101 and additional full-time equivalents and other support dedicated to discovery, preclinical, and manufacturing activities at Array BioPharma. The Company also recognized R&D-related stock-based compensation expense of $0.9 million during the second quarter of 2015 compared to $0.3 million for the second quarter of 2014.

Research and development expenses were $9.5 million for the six months ended June 30, 2015 compared to $4.8 million for the six months ended June 30, 2014. The increase was primarily due to expanded clinical development activities for LOXO-101 and additional full-time equivalents and other support dedicated to discovery, preclinical, and manufacturing activities at Array BioPharma. The Company also recognized R&D-related stock-based compensation expense of $1.4 million during the six months ended June 30, 2015 compared to $0.3 million for the six months ended June 30, 2014.

General and administrative expenses were $2.4 million for the second quarter 2015 compared to $1.2 million for the second quarter 2014. The increase was primarily due to additional full-time equivalents, increased compensation costs and increased costs associated with operating as a public company. The Company also recognized G&A-related stock-based compensation expense of $0.8 million during the second quarter of 2015 compared to $0.2 million for the second quarter of 2014.

General and administrative expenses were $4.8 million for the six months ended June 30, 2015 compared to $2.0 million for the six months ended June 30, 2014. The increase was primarily due to additional full-time equivalents, increased compensation costs and increased costs associated with operating as a public company. The Company also recognized G&A-related stock-based compensation expense of $1.3 million during the six months ended June 30, 2015 compared to $0.2 million for the six months ended June 30, 2014.

Net loss attributable to common shareholders was $8.1 million and $14.2 million for the three and six months ended June 30, 2015, respectively, compared to $3.9 million and $6.8 million for the three and six months ended June 30, 2014, respectively.

On August 5, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported two research projects involving the company’s Lm Technology immunotherapy candidate ADXS-PSA, which is being developed for prostate cancer, have been selected as 2015 Movember Foundation-PCF Challenge Awards, sponsored by the Movember Foundation and the Prostate Cancer Foundation (PCF) (Press release, Advaxis, AUG 5, 2015, View Source [SID:1234507025]). Grants amounting to $1 million each have been awarded to two ADXS-PSA teams conducting innovative large-scale research projects concerning metastatic, treatment-resistant prostate cancer, an advanced form of the disease with often-lethal outcomes.

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The Movember Foundation-PCF Challenge Awards support cross-disciplinary teams of investigators conducting pioneering research to address critical, unmet medical needs for prostate cancer patients. These highly competitive awards make large investments in multi-year projects that may fall outside the parameters of traditional funding organizations. Each proposal submitted to PCF was subjected to a rigorous peer review process that assessed the scientific merit of the project as well as its potential impact for patients. To date, the Movember Foundation has donated approximately $39 million to PCF to support innovative prostate cancer research, funding 28 research awards in the U.S., Canada and Great Britain.

Both ADXS-PSA projects awarded involve principal investigator Adam P. Dicker, M.D., Ph.D., Chair of the Department of Radiation Oncology at the Sidney Kimmel Cancer Center at Thomas Jefferson University, and will evaluate progression-free survival (PFS) as the primary endpoint and look at deep sequencing of T cell receptors to follow expansion of specific T cell clones.

"I look forward to having the opportunity to explore the potential of ADXS-PSA as immunotherapy in locally advanced and metastatic prostate cancer in two clinical trials," said Dr. Dicker. "These trials will help further the scientific understanding on the effects of targeting the prostate-specific antigen associated with prostate cancer."

The following ADXS-PSA proposals were selected to receive funding:

The first proposal, "CARAVAN (Checkpoint-Radiation-Vaccine Neoadjuvant) trial for metastatic prostate cancer," is led by researchers at the Sidney Kimmel Cancer Center at Thomas Jefferson University (Adam P. Dicker, M.D., Ph.D.) and the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center (Lawrence Fong, M.D.). This is a Phase 1/2 study investigating intraprostatic anti-CTLA-4 and PD-1 blockade, plus radiation and ADXS-PSA in metastatic prostate cancer (N= ~42 +/-, its variable).

The second proposal, "Altering the natural history of metastatic prostate cancer using stereotactic ablative radiotherapy and immune stimulation," is led by researchers at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Phuoc T. Tran, M.D., Ph.D. and Ashley Ross, M.D., Ph.D.) and Sidney Kimmel Cancer Center at Thomas Jefferson University (Adam P. Dicker, M.D., Ph.D.). This is a Phase 1/2 study that combines stereotactic ablative radiation to prostate cancer metastases, followed by treatment with ADXS-PSA (N= ~36).

"We are tremendously honored to have ADXS-PSA recognized and supported in this way by the 2015 Movember Foundation-PCF Challenge Awards," said David J. Mauro, M.D., Ph.D., Executive Vice President and Chief Medical Officer of Advaxis. "This funding will bring about the research necessary to potentially bring ADXS-PSA immunotherapy to people with metastatic prostate cancer, a disease that is expected to take the lives of 27,540 men in 2015."

Advaxis recently announced that enrollment has initiated in the Phase 1/2 KEYNOTE-046 clinical trial evaluating the combination of ADXS-PSA and Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with previously treated, metastatic castration-resistant prostate cancer (mCRPC). KEYNOTE-046 is the first-in-human study of ADXS-PSA and the second study initiated to evaluate the use of KEYTRUDA in the treatment of advanced prostate cancer. Data from preclinical studies suggest that Advaxis’s Lm Technology immunotherapies in combination with a PD-1 antibody may lead to an enhanced anti-tumor immune response.

About the Prostate Cancer Foundation

The Prostate Cancer Foundation (PCF) is the world’s leading philanthropic organization funding and accelerating prostate cancer research. Founded in 1993, PCF has raised more than $615 million and provided funding to more than 2,000 research programs at nearly 200 cancer centers and universities. The PCF global research enterprise now extends to 19 countries. PCF advocates for greater awareness of prostate cancer and more efficient investment of governmental research funds for transformational cancer research. Its efforts have helped produce a 20-fold increase in government funding for prostate cancer. For more information, click here.

About the Movember Foundation

The Movember Foundation is a global charity raising funds and awareness for men’s health. These funds deliver breakthrough research and support services to allow men to live longer, healthier, happier lives. Since 2003, millions have joined the men’s health movement, raising more than $650 million and funding over 1,000 programs through impact investments, focusing on prostate cancer, testicular cancer and poor mental health.

The Foundation runs awareness and fundraising activities year-round, with the annual Movember campaign in November being globally recognized for its fun and innovative approach to raising money and getting men to take action for their health. During Movember, we challenge men to grow a moustache or to make a commitment to get active and MOVE, both of which are about real action for health and are done to spark conversation and raise vital funds and awareness. The Foundation’s vision is to have an everlasting impact on men’s health.

Movember is fully accredited by the Better Business Bureau, and for the past three years, has been named a Top 100 best NGO by The Global Journal. For more information please visit Movember.com. Movember is a registered 501(c)(3) charity.

About the KEYNOTE-046 Trial

KEYNOTE-046 is a multicenter, dose determining, open-label Phase 1/2 study designed to evaluate the safety and efficacy of ADXS-PSA as a monotherapy and in combination with KEYTRUDA in approximately 51 mCRPC patients. Part A of the study will be a dose escalating study designed to establish the maximum tolerated dose of ADXS-PSA as a monotherapy. Part B will consist of a dose escalating trial of ADXS-PSA in combination with KEYTRUDA, followed by an expansion cohort phase. The primary objective is to evaluate safety and tolerability of the two immunotherapies, with the secondary objective to evaluate anti-tumor activity and PFS. Further information about KEYNOTE-046 can be found on ClinicalTrials.gov, using Identifier NCT02325557.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that approximately 220,800 new cases of prostate cancer will be diagnosed and about 27,540 men are expected to die of the disease in 2015.

About ADXS-PSA

ADXS-PSA is an Lm Technology immunotherapy that is designed to target the prostate-specific antigen (PSA), a protein produced exclusively by prostate cells that is associated with prostate cancer. ADXS-PSA secretes the PSA antigen, fused to the powerful immunostimulant tLLO, directly inside the antigen presenting cells that are capable of driving a cellular immune response to PSA expressing cells. This approach is also designed to inhibit the Treg and myeloid-derived suppressor cells (MDSCs) that contribute to immunologic tolerance of prostate cancer. In preclinical analysis, ADXS-PSA inhibits the immunosuppression caused by Treg and MDSC cells localized inside tumors that may promote immunologic tolerance of prostate cancer.

(Filing, 10-Q, ArQule, AUG 5, 2015, View Source [SID:1234507031])

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