On November 4, 2015 Array BioPharma Inc. (NASDAQ: ARRY) reported results for the first quarter of its fiscal year ending June 30, 2016 and provided an update on progress on its key clinical development programs (Press release, Array BioPharma, NOV 4, 2015, View Source;p=RssLanding&cat=news&id=2106469 [SID:1234507941]).

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Ron Squarer, Chief Executive Officer of Array, noted, "The first quarter has been a period of important progress as we continue to advance binimetinib and encorafenib, two innovative oncology products in Phase 3, toward 2016 regulatory submissions. Recently presented data supports the value of our BRAF-mutant melanoma and BRAF-mutant colorectal cancer programs by showing the potential for differentiation compared to other approaches."

KEY PIPELINE UPDATES

Binimetinib (MEK162) and encorafenib (LGX818)

NEMO (binimetinib / NRAS-mutant melanoma) and COLUMBUS Part 1 and Part 2 (binimetinib and encorafenib / BRAF-mutant melanoma) target enrollment achieved
NEMO and COLUMBUS top-line results expected in 2H 2015 and 1H 2016, respectively
BRAF- and NRAS-melanoma trial results presented at ESMO (Free ESMO Whitepaper) European Cancer Congress (ECC)

Update on Phase 3 trials

In April 2015, the NEMO Phase 3 study completed patient enrollment and Array expects top-line results by year end and a regulatory filing in the first half of 2016. In addition, the COLUMBUS (Part 1) study also completed enrollment in April 2015 and Array expects top-line results and reaffirms a projected regulatory filing of binimetinib and encorafenib in 2016. In October 2015, COLUMBUS (Part 2) achieved its target patient enrollment. The MILO Phase 3 trial in patients with low-grade serous ovarian cancer continues to enroll patients, and Array estimates the availability of top-line data from MILO, along with a projected regulatory filing, in 2017.

New BRAF-mutant melanoma interim results

LOGIC2 is an ongoing 140-patient, two-part study designed to explore the safety and activity of novel triplet combinations in BRAF-mutant melanoma. In Part 1, patients are treated with the combination of binimetinib and encorafenib until disease progression. Based on the results of molecular profiling at that time, each patient is assigned to one of four arms containing a triplet combination of binimetinib, encorafenib and a third innovative targeted therapy. Results from Part 1 of the study were reported separately for patients who have previously received a BRAF and/or MEK inhibitor versus those who were initially naïve to BRAF and MEK inhibitor treatment.

In Part 1, patients are treated with binimetinib 45 mg twice daily (BID) and encorafenib 450 mg once daily (QD), the same doses evaluated in the ongoing Phase 3 COLUMBUS trial. Interim results from this study were presented at ESMO (Free ESMO Whitepaper) ECC in September 2015. In the BRAF/MEK-naïve group (n=40), the interim overall response rate (confirmed and unconfirmed complete response or partial response) was 68%, with a 6-month progression-free survival estimate of 79%. Of note, 96% of patients in this group continued to receive study treatment as of the data cutoff. Preliminary data from all patients in the study (n=89) also indicate that the combination of binimetinib and encorafenib showed good tolerability with a 12% incidence of pyrexia and little to no rash or photosensitivity. These results indicate that the combination of binimetinib and encorafenib show encouraging clinical activity and an emerging differentiated tolerability profile relative to other MEK/BRAF inhibitor combinations.

New NRAS-mutant melanoma interim results

Promising preliminary antitumor activity from a Phase 1b/2 study of binimetinib in combination with ribociclib (Novartis, LEE011), a CDK4/6 inhibitor, in NRAS-mutant melanoma patients, was presented at ESMO (Free ESMO Whitepaper) ECC. Results were shared from 45 patients enrolled in the dose escalation portion of the study, which included two dosing schedules (28-day or 21-day cycles). For the 28-day dosing schedule, patients received continuous twice daily dosing of binimetinib while receiving ribociclib for 21 days per 28 day cycle. For the 21-day schedule, both agents were delivered for 14 days of a 21 day cycle.

For patients receiving the combination on a 28-day cycle (n=22), the Objective Response Rate (ORR, confirmed and unconfirmed complete or partial responses) was 41%, the Disease Control Rate (DCR, confirmed and unconfirmed complete or partial responses and stable disease) was 82% with a median Progression Free Survival (mPFS) of 6.7 months. Furthermore, the ORR was 56% (n=9) for patients receiving dose level 1 of the 28-day schedule consisting of binimetinib 45 mg BID and the lowest dose of ribociclib (200 mg QD), indicating that robust activity can be achieved with this dose and schedule. Common treatment-related adverse events included elevated creatine phosphokinase (CPK), skin and gastrointestinal events. Investigation of the alternative 21-day schedule is ongoing.

Update on European partnership

Array expects to complete a European partnership for both binimetinib and encorafenib by year end and will provide further updates as appropriate.

Selumetinib (partnered with AstraZeneca) – Three registration trials advancing in NSCLC (SELECT-1), thyroid cancer (ASTRA) and neurofibromatosis type 1

AstraZeneca continues to advance selumetinib in three registration trials: SELECT-1 in patients with KRAS-mutant non-small cell lung cancer, a registration trial in patients with neurofibromatosis type 1 and ASTRA in patients with differentiated thyroid cancer. AstraZeneca expects to share top-line results from SELECT-1 in 2016.

ARRY-797 (ARRY-371797) – Phase 2 trial on-going in patients with LMNA A/C-related dilated cardiomyopathy (DCM)

Array is conducting a 12-patient Phase 2 study to evaluate the effectiveness and safety of ARRY-797 in patients with LMNA A/C-related DCM, a serious, genetic cardiovascular disease. By age 45, approximately 70% of patients with LMNA A/C-related DCM experience cardiovascular death, transplant or a major cardiac event. Currently, Array has patients on this trial past 48 weeks and ARRY-797 has been well-tolerated. Patients completing this Phase 2 trial are being enrolled in a roll-over study to continue treatment. Interim data continue to be encouraging for multiple endpoints across patients, but further data are needed to fully assess the magnitude, consistency and durability of effects.

Filanesib (ARRY-520) – Two Phase 2 studies nearing completion; No current plans to initiate additional clinical trials with filanesib

Given Array’s significant opportunity with the Phase 3 binimetinib and encorafenib programs across a number of cancer indications, Array currently has no plans to initiate additional trials with filanesib, a highly selective, targeted KSP inhibitor. Two studies in patients with relapsed / refractory multiple myeloma are nearing completion: a randomized Phase 2 trial of the combination of filanesib and Kyprolis (carfilzomib) and Kyprolis alone (ARRAY-520-216) and the AfFIRM trial, a Phase 2 single agent study. Array expects to present interim data from the ARRAY-520-216 study at a scientific conference by the end of the year.

LEADERSHIP

Array appoints Patricia Henahan to Chief Financial Officer

Array appointed Patricia Henahan to the position of Chief Financial Officer. Ms. Henahan has extensive financial experience in the biopharmaceutical industry including leadership roles at Hospira, AstraZeneca, Eli Lilly and MedImmune. She has strong expertise in strategic planning, financial analysis, commercialization, R&D, operations and alliance management. Prior to joining Array, Ms. Henahan was Vice President of Finance for Hospira’s $3 billion U.S. pharmaceutical-focused business. During her tenure, Hospira delivered double-digit profit growth and achieved its highest ever U.S. market share and revenue level.

FINANCIAL HIGHLIGHTS

Cash, cash equivalents, marketable securities and accounts receivable totaled $173.3 million at the end of the quarter. Accounts receivable primarily consist of receivables expected to be paid by Novartis within three months. In March 2015, two clinical programs, binimetinib and encorafenib, became wholly-owned assets which prompted changes to our classification of revenue and expenses for the programs. The new expense classifications were included in the fourth quarter of fiscal 2015 financial results and, beginning in the current quarter, Array reports revenue from Novartis reimbursements as a separate line item called "reimbursement revenue."

First Quarter of Fiscal 2016 Compared to Fourth Quarter of Fiscal 2015 (Sequential Quarters Comparison)

Revenue for the first quarter of fiscal 2016 was $16.2 million, compared to $12.3 million for the prior sequential quarter. The $3.9 million increase in revenue was primarily due to higher reimbursement revenue from Novartis. Cost of partnered programs for the first quarter of fiscal 2016 was $6.2 million, compared to $7.0 million for the prior quarter. Research and development expense was $21.0 million, compared to $18.6 million in the prior quarter. The increase in research and development expense is primarily related to the ongoing transition of binimetinib and encorafenib trials from Novartis to Array. Net loss for the first quarter was $21.0 million, or ($0.15) per share, and was $12.7 million, or ($0.09) per share in the prior quarter as the fourth quarter of fiscal 2015 was favorably impacted by a $11.5 million in gains from the sale of marketable securities and our CMC business.

First Quarter of Fiscal 2016 Compared to First Quarter of Fiscal 2015 (Prior Year Comparison)

Compared to the same quarter of fiscal 2015, revenue for the first quarter of fiscal 2016 increased $10.1 million primarily due to $9.6 million in reimbursement revenue from Novartis. Cost of partnered programs decreased $6.0 million compared to the first quarter of fiscal 2015 primarily due to binimetinib development costs being presented as research and development expense instead of cost of partnered programs upon becoming wholly-owned programs. Research and development expense increased $8.8 million compared to the first quarter of fiscal 2015 due to the categorization of binimetinib costs, as well as new spending on encorafenib, which was not an Array asset in the prior year period. Net loss for the first quarter of fiscal 2016 was $21.0 million, or ($0.15) per share, and was $27.6 million, or ($0.21) per share, for the same quarter in fiscal 2015.

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On November 04, 2015 ArQule, Inc. (NASDAQ:ARQL) reported its financial results for the third quarter of 2015 (Press release, ArQule, NOV 4, 2015, View Source [SID:1234507939]).

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For the quarter ended September 30, 2015, the Company reported a net loss of $2,354,000 or $0.04 per share, compared to a net loss of $6,399,000 or $0.10 per share, for the third quarter of 2014. For the nine-month period ended September 30, 2015, the Company reported a net loss of $10,922,000 or $0.17 per share, compared to a net loss of $19,879,000 or $0.32 per share for the nine-month period ended September 30, 2014.

At September 30, 2015, the Company had a total of $43,759,000 in cash, equivalents and marketable securities.

Key Highlights

Tivantinib phase 2 data in hepatocellular carcinoma presented at International Liver Cancer Association (ILCA) Conference supports tumor MET status as a prognostic and predictive biomarker: The biomarker-driven phase 3 trial for tivantinib, METIV-HCC, in second line hepatocellular carcinoma (HCC) is expected to complete patient accrual by year end. The METIV-HCC trial is randomized 2:1 against best supportive care and will enroll approximately 300 MET-high patients with the primary end-point of overall survival.

Exercise of co-commercialization option for tivantinib in the U.S.: The Company exercised its co-commercialization option under its collaboration agreement with partner, Daiichi Sankyo; if the METIV-HCC trial is approved by regulatory authorities, the first commercial indication for tivantinib would be second-line HCC.

ESMO presentation and PLOS ONE publication support AKT1 and PI3K mutations as targets for ARQ 092 and ARQ 751 – fifth partial response (PR) observed in phase 1b trial: A phase 1b trial of ARQ 092 as a single agent is on-going in lymphoma, endometrial and other cancers harboring the AKT1 or P13K mutations. Five PRs have now been observed in 27 patients who have been dosed in the trial thus far.

Phase 1 trial for Proteus syndrome with ARQ 092 is open for enrollment: Our collaborator, the National Institutes of Health (NIH), has completed pre-trial preparations and recently opened the site for enrollment.

Phase 2 trial for ARQ 087 in intrahepatic cholangiocarcinoma (iCCA) continues to enroll: Five sites are now open and enrolling in the U.S. for iCCA patients with the FGFR translocation. Additional sites in Italy are expected to be enrolling shortly. 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.

Updated 2015 financial guidance reflects disciplined cost controls resulting in higher expected 2015 year-end cash balance: ArQule now expects net use of cash to be between $22 and $24 million for 2015. The company expects to end 2015 with between $37 and $39 million in cash, equivalents and marketable securities, an increase from the previous guidance of $32 to $35 million.

"The last few months have been very productive for ArQule from both an operational and pipeline development standpoint," said Paolo Pucci, Chief Executive Officer of ArQule. "As we are approaching the completion of recruitment for the METIV-HCC trial we have exercised our co-commercialization option with Daiichi Sankyo in the U.S. for tivantinib. We are also making progress with ArQule’s proprietary pipeline which continues to show promising results in multiple biomarker-driven trials."

"We continue to show excellent progress in our AKT program with the achievement of the fifth PR in the phase 1b expansion cohort," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "These data validate the preclinical hypothesis underlying the recently published PLOS ONE manuscript. We will be presenting additional data on ARQ 092 and ARQ 751, as well as tivantinib and ARQ 087, at the AACR (Free AACR Whitepaper)-NCI-EORTC conference, triple meeting, in Boston this weekend. We are also looking forward to our collaborator, the NIH, dosing the first patient with ARQ 092 in Proteus syndrome."

"In summary, we had a very strong quarter," said Mr. Pucci. "In addition to progress across our clinical pipeline we also announced revised 2015 financial guidance to reflect a higher cash balance expected at year-end."

Revenues and Expenses

The Company reported research and development revenue of $2,653,000 for the quarter ended September 30, 2015, compared with $2,662,000 for the quarter ended September 30, 2014. For the nine-month period ended September 30, 2015, research and development revenue for the company was $8,442,000, compared with $8,239,000 for the nine-month period ended September 30, 2014.

Research and development revenue in the three and nine months ended September 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 nine month period is due to higher revenue from our Daiichi Sankyo tivantinib program.

Total costs and expenses for the quarter ended September 30, 2015 were $5,019,000 compared to $9,110,000 for the third quarter of 2014. For the nine-month period ended September 30, 2015, total costs and expenses were $19,722,000 compared with $28,398,000 for the nine-month period ended September 30, 2014.

Research and development costs for the three and nine months ended September 30, 2015 were $3,180,000 and $11,920,000 respectively, compared with $5,014,000 and $17,981,000 for three and nine-month periods of 2014.

Research and development expense in the quarter ended September 30, 2015 decreased by $1.8 million primarily due to lower labor related costs of $0.5 million from reduced headcount, outsourced clinical and product development costs of $0.6 million, facility costs of $0.6 million and lab expenses of $0.1 million.

Research and development expense in the nine months ended September 30, 2015 decreased by $6.1 million primarily due to lower labor related costs of $2.2 million from reduced headcount, outsourced clinical and product development costs of $1.7 million, facility costs of $1.4 million and lab expenses of $0.7 million.

General and administrative expense for three and nine-month periods ended September 30, 2015 were $1,839,000 and $7,802,000 respectively, compared to $2,997,000 and $9,318,000 for the three and nine-month periods of 2014.

General and administrative expense decreased by $1.2 million in the quarter ended September 30, 2015 principally due to lower facility costs of $0.9 million and labor related costs from reduced headcount of $0.2 million.

General and administrative expense decreased by $1.5 million in the nine months ended September 30, 2015 principally due to lower facility costs of $0.7 million and labor related costs of $0.6 million from reduced headcount.

Restructuring and other costs for the three and nine months ended September 30, 2014 were $1.1 million. There were no restructuring expenses incurred in the three or nine-month periods ended September 30, 2015.

Updated 2015 Guidance

For 2015, ArQule expects net use of cash to range between $22 and $24 million. Revenues are expected to range between $10 and $11 million. Net loss is expected to range between $13 and $15 million, and net loss per share is expected to range between $(0.21) and $(0.24). ArQule expects to end 2015 with between $37 and $39 million in cash, equivalents and marketable securities.

On November 4, 2015 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutic candidates that regulate cellular growth and repair, reported a corporate update and reported financial results for the third quarter ended September 30, 2015 (Press release, Acceleron Pharma, NOV 4, 2015, View Source [SID:1234507937]).

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"We made significant progress across our clinical pipeline in the quarter and are poised, with our partner Celgene, to launch two pivotal Phase 3 programs by year-end," said John Knopf, Ph.D., Chief Executive Officer of Acceleron. "We also revealed new clinical data showing unprecedented results with our locally delivered muscle agent, ACE-083. Finally, our discovery team continues to innovate with the introduction of our new IntelliTrap platform, to discover selective and novel compounds targeting the transforming growth factor-beta superfamily of proteins."

Recent Highlights and Current Updates

Development Programs

Hematology

Acceleron and Celgene plan to initiate Phase 3 studies with luspatercept in beta-thalassemia, the BELIEVE trial, and myelodysplastic syndromes (MDS), the MEDALIST trial, by the end of 2015.

Completed enrollment and treatment in the luspatercept Phase 2 dose escalation and expansion studies in MDS and beta-thalassemia.

Treatment continues in Phase 2 long-term extension studies with luspatercept in beta- thalassemia and MDS.
Amended and expanded Phase 2 MDS study. Additional study cohorts have been added to evaluate the effects of luspatercept in lower risk MDS patients that are either erythropoietin-stimulating agent (ESA) treatment naïve or ring sideroblast negative.

Muscle Diseases

Announced initial Phase 1 data on ACE-083, Acceleron’s therapeutic candidate designed to increase muscle mass and strength when delivered locally to targeted muscle groups. Acceleron reported an unprecedented 14.5% mean increase in muscle volume in the injected muscle of the quadriceps. The Company plans to begin a Phase 2 trial in facioscapulohumeral muscular dystrophy (FSHD) in mid-2016.

Presented preclinical data on ACE-083 at the 20th Annual International Congress of the World Muscle Society. ACE-083 produced significant increases in muscle mass of approximately 75% in the injected muscle with no observed effect on either the uninjected contralateral muscle or on whole body mass. Increases in muscle mass were associated with a significant increase in muscle force and power of approximately 40%.

Introduced ACE-2494, Acceleron’s first IntelliTrap molecule, designed for systemic administration to increase muscle mass and strength. In mice, ACE-2494 generated dose dependent increases in muscle mass at a magnitude comparable to the powerful effects of soluble ActRIIB fusion proteins. After 4 weeks of treatment, ACE-2494 (10 mg/kg twice weekly) generated increases in muscle mass ranging from 41% to 87% across different muscle groups. The Company expects to begin clinical studies with ACE-2494 by the end of 2016.

Oncology

FDA granted Fast Track Designation for dalantercept in combination with axitinib for the treatment of patients with advanced renal cell carcinoma (RCC), following treatment with an anti-angiogenic agent.
Presented RCC Phase 2 data showing that the combination of dalantercept and axitinib generated encouraging, progression-free survival after one year. The Company reported the 12-month Kaplan Meier estimate for a progression-free survival rate of 39% for the combination of dalantercept plus axitinib in patients with advanced RCC in Part 1 of the Phase 2 DART study. This compares favorably to the 12-month PFS rate of 25% with axitinib alone.

Nephrology

Acceleron and Celgene will refocus the development of sotatercept in the pre-dialysis chronic kidney disease setting. The Companies plan to meet with regulators in the first half of 2016 to discuss study designs.

Research and Development

Acceleron introduced its new IntelliTrap discovery platform. The IntelliTrap platform is designed to generate dozens of highly selective molecules that optimally target the transforming growth factor-beta superfamily to discover innovative new therapies.

Upcoming Milestones and Events

Initiation of the pivotal Phase 3 clinical trials with luspatercept in MDS and beta-thalassemia is expected by year-end.
Additional luspatercept data from ongoing Phase 2 MDS and beta-thalassemia studies will be presented at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), December 5-8, 2015 in Orlando, Florida.
ACE-083 Phase 1 clinical data will be presented at the 8th International Conference on Cachexia, Sarcopenia and Muscle Wasting, December 4-6, 2015, in Paris, France.

Clinical and preclinical data will be presented at the American Society of Nephrology Kidney Week, November 3-8, 2015, in San Diego, CA.

Financial Results

Cash Position – Cash, cash equivalents and investments as of September 30, 2015 were $148.1 million. As of December 31, 2014 the company had cash and cash equivalents of $176.5 million. Acceleron expects that its cash, cash equivalents and investments as of September 30, 2015 will be sufficient to fund the Company’s operations into the second half of 2017.