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Five Prime Announces Second Quarter 2016 Results and Provides Business Update

On August 4, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported a corporate update and reported financial results for the second quarter ended June 30, 2016 (Press release, Five Prime Therapeutics, AUG 4, 2016, View Source [SID:1234514240]).

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"We’re pleased with the progress we’ve made through the first half of the year and remain on track with our clinical programs," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "At ASCO (Free ASCO Whitepaper) in June, we announced early but encouraging Phase 1 data for our FGFR2b antibody, FPA144, including confirmed partial responses in three of nine patients with FGFR2b+ gastric tumors and one confirmed complete response in a patient with bladder cancer. Notably, FPA144 recently received FDA Orphan Drug Designation in patients with FGFR2b+ gastric cancer. Development of our anti-CSF1R antibody, FPA008, now named cabiralizumab, is also progressing according to plan. We still expect the Phase 1b dose expansion portion of the trial combining cabiralizumab with OPDIVO (nivolumab) in multiple tumor types to begin during the second half of 2016. Also on track is our Phase 2 clinical trial of cabiralizumab in patients with pigmented villonodular synovitis (PVNS), a rare indication for which we received FDA Orphan Drug Designation."

Business Highlights and Recent Developments

Clinical Pipeline:

FPA008 (cabiralizumab): an investigational antibody that inhibits CSF1R and has been shown to block the activation and survival of monocytes and macrophages. In some cancers, macrophages suppress the immune system’s ability to kill cancer cells. In pigmented villonodular synovitis (PVNS), macrophages form the bulk of the tumor mass in joints. Cabiralizumab blocks the activation and survival of these cell types. Five Prime and Bristol-Myers Squibb (BMS) have an exclusive worldwide collaboration agreement for the development and commercialization of cabiralizumab.

Advanced Phase 1a/1b cabiralizumab/OPDIVO combination trial.
Five Prime continued dose exploration in the Phase 1a/1b clinical trial evaluating the safety, tolerability and preliminary efficacy of the immunotherapy combination of cabiralizumab with OPDIVO, BMS’s PD-1 immune checkpoint inhibitor. The trial is currently expected to enroll up to 280 patients and remains on target to move into Phase 1b during the second half of 2016.

Advanced clinical trial of cabiralizumab in patients with PVNS into Phase 2 in May.
Five Prime advanced cabiralizumab into the Phase 2 dose expansion portion of the ongoing Phase 1/2 trial in PVNS, a CSF-1 receptor-driven tumor. The Phase 2 portion is evaluating clinical measures including response rate, pain and range of motion in approximately 30 PVNS patients. The U.S. Food and Drug Administration (FDA) granted cabiralizumab Orphan Drug Designation for the treatment of PVNS. Five Prime estimates the U.S. prevalence for diffuse PVNS patients may be as high as 25,000 patients.

FPA144: an isoform-selective antibody in development as a targeted immuno-therapy for tumors that over-express FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. FPA144 has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells.

In July, received FDA Orphan Drug Designation for FPA144 for the treatment of gastric cancer and cancer of the gastroesophageal junction in patients whose tumors overexpress FGFR2b.

Presented data from the ongoing Phase 1 trial of FPA144 in an oral session at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June.

FPA144 monotherapy demonstrated early evidence of anti-tumor efficacy in gastric cancer patients with FGFR2b protein overexpression from Part 1b and Part 2 of the trial. These heavily pre-treated patients had received between 1 and 6 prior therapies with a median of 2 prior therapies. The highlights of the data presented at ASCO (Free ASCO Whitepaper) include:

Efficacy as of the April 1, 2016 data cutoff:
3 confirmed partial responses (PRs) out of 9 gastric cancer patients treated (33%); 1 of these 3 PRs was confirmed after the data cutoff
7 of 9 gastric cancer patients with disease control (3 PRs + 4 stable disease), disease control rate (DCR) = 77%
12-week progression-free survival (PFS) in 6 of 9 gastric cancer patients (67%)
Median duration of treatment of 112 days (range 42-182 days), with 2 of 9 gastric cancer patients still on study
A patient with metastatic bladder cancer in the dose escalation portion of the trial in solid tumors achieved a confirmed complete response (CR)

In addition to the 3 PRs in gastric cancer noted above, there was an additional unconfirmed PR in the 10th gastric cancer patient with FGFR2b protein overexpression, whose scan became available after the data cutoff.
Safety as of the April 1, 2016 data cutoff:

No dose-limiting toxicities (DLTs); maximum-tolerated dose (MTD) was not reached
No treatment-related serious adverse events (SAEs)
The most common treatment-related AEs ( > 5%) were all grades 1 or 2: fatigue (22.5%), nausea (20%) and vomiting (12.5%)

Presented preclinical data for FPA144 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. FPA144 was featured in two presentations at the AACR (Free AACR Whitepaper) Annual Meeting in April 2016. Five Prime demonstrated that FPA144’s enhanced ADCC mechanism drives innate and adaptive immune responses in the tumor microenvironment, recruiting NK and T cells into the tumor. Additionally, FPA144 produced an additive effect on tumor growth inhibition when combined with PD-1 blockade. These pre-clinical findings suggest the therapeutic potential for a combination of FPA144 with a checkpoint inhibitor.

FP-1039: a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to and neutralizes FGF ligands (such as FGF2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells.

GSK presented data in mesothelioma patients from the ongoing Phase 1b trial of FP-1039 at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting.

Although GSK has terminated its FP-1039 license from Five Prime, GSK is continuing to conduct the ongoing study of FP-1039 in combination with 1st-line pemetrexed and cisplatin in patients with untreated, unresectable mesothelioma. GSK has now capped the trial at the 25 patients enrolled at the 15 mg/kg dose.

The trial data are not sufficiently mature for Five Prime to make decisions yet on potential future development of FP-1039 in mesothelioma. Those decisions will be based on our future assessment of the response rate and durability in this trial, as well as other considerations, such as drug supply and manufacturing.
Preclinical Research and Development:

Progressed internal immuno-oncology research programs. Five Prime continues to advance multiple immuno-oncology candidates through preclinical development and expects to have two programs entering pre-IND studies before the end of 2016. The company anticipates filing one IND by the end of 2017 and to have preclinical assets sufficient to keep the pace of one IND per year for the foreseeable future.

GSK licensed intellectual property for respiratory disease target identified using Five Prime’s proprietary protein discovery platform. In June, GSK exercised its option to take an exclusive license to the intellectual property related to a target under the 2012 respiratory diseases research collaboration between the companies. This triggered a $1.5 million license payment to Five Prime, which was recognized as revenue in the second quarter. Five Prime is eligible to receive up to $92.75 million in contingent milestone payments for each product that targets the licensed protein.
Summary of Financial Results and Guidance:

Cash Position. Cash, cash equivalents and marketable securities totaled $469.2 million on June 30, 2016, compared to $517.5 million on December 31, 2015. The decrease in cash was primarily attributable to cash used in operations to advance the FPA144 clinical trial, preclinical programs and tax payments.

Revenue. Collaboration revenue for the second quarter of 2016 increased by $2.9 million to $9.2 million from $6.3 million in the second quarter of 2015. This increase was primarily due to revenue recognized under the 2015 cabiralizumab collaboration agreement with BMS, under which Five Prime is reimbursed for the immuno-oncology trial expenses.

R&D Expenses. Research and development expenses for the second quarter of 2016 increased by $8.9 million, or 66.9%, to $22.2 million from $13.3 million in the second quarter of 2015. This increase was primarily related to advancing the FPA144 clinical trial, preclinical development and immuno-oncology research programs.

G&A Expenses. General and administrative expenses for the second quarter of 2016 increased by $3.5 million, or 76.1%, to $8.1 million from $4.6 million in the second quarter of 2015. This increase was primarily due to increases in cash and stock-based compensation expenses.

Net Loss. Net loss for the second quarter of 2016 was $13.1 million, or $0.49 per basic and diluted share, compared to a net loss of $11.5 million, or $0.45 per basic and diluted share, for the second quarter of 2015.

Shares Outstanding. Total shares outstanding were 28.3 million as of June 30, 2016.

Cash Guidance. Five Prime continues to expect full-year 2016 net cash used in operating activities to be less than $120 million, comprising less than $90 million used in operations and less than $30 million used for tax payments. The company estimates ending 2016 with approximately $400 million in cash, cash equivalents and marketable securities.

Curis Reports Second Quarter 2016 Financial Results

On August 04, 2016 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, reported its financial results for the second quarter ended June 30, 2016 (Press release, Curis, AUG 4, 2016, View Source [SID:1234514237]).

"We are pleased that dosing of patients has started in the Phase 1 trial of CA-170, the first oral, small molecule immune checkpoint inhibitor targeting PD-L1 and VISTA pathways from our collaboration with Aurigene," said Ali Fattaey, Ph.D., Curis’s President and CEO. "Additionally, the second immuno-oncology program in our Aurigene collaboration that is focused on oral small molecules that target PD-1 and TIM3 pathways continues to progress well, further supporting our strategy to address inhibitory immune checkpoints with oral small molecules."

Dr. Fattaey continued, "We continue to enroll patients in the Phase 2 trial of CUDC-907 in patients with relapsed/refractory diffuse large B cell lymphoma or DLBCL, to assess its efficacy specifically in patients with MYC—altered DLBCL and remain on track for data in 2017."

Second Quarter 2016 Financial Results

Curis reported a net loss of $11.3 million, or ($0.09) per share on both a basic and diluted basis for the second quarter of 2016, as compared to a net loss of $8.1 million, or ($0.06) per share on both a basic and diluted basis for the same period in 2015. Curis reported a net loss of $20.7 million or ($0.16) per share on both basic and diluted basis for the six months ended June 30, 2016, as compared to a net loss of $40.0 million, or ($0.34) per share on both basic and diluted basis for the same period in 2015. The net loss for the six months ended June 30, 2015 includes a non-cash in-process research and development charge of $24.3 million related to Curis’s license agreement with Aurigene.

Revenues for the second quarter of 2016 were $1.7 million, as compared to $2.1 million for the same period in 2015. Revenues for both periods comprise primarily royalty revenues recorded on Genentech and Roche’s net sales of Erivedge. Revenues for the six months ended June 30, 2016 were $3.4 million, as compared to $3.7 million for the same period in 2015.

Operating expenses were $12.4 million for the second quarter of 2016, as compared to $9.5 million for the same period in 2015.

Operating expenses for the six months ended June 30, 2016 were $22.9 million, as compared to $42.1 million for the same period in 2015, and comprised the following:

Costs of Royalty Revenues. Costs of royalty revenues, primarily amounts due to third-party university patent licensors in connection with Genentech and Roche’s Erivedge net sales, were $0.1 million for both the second quarter of 2016 and 2015. Cost of royalty revenues for the six months ended June 30, 2016 and 2015 were $0.2 million for both periods.

In-Process Research and Development Expense. No in-process research and development expenses were recorded for the six months ended June 30, 2016 as compared to $24.3 million recorded during the same period in 2015 associated with the issuance of 17,120,131 shares of Curis common stock to Aurigene as partial consideration for the rights granted under the terms of the January 2015 collaboration agreement.

Research and Development Expenses. Research and development expenses were $8.8 million for the second quarter of 2016, as compared to $5.9 million for the same period in 2015. The increase was primarily due to increased direct spending related to clinical activities of CUDC-907 and programs under the Aurigene collaboration over the prior year period, including a $3.0 million milestone payment to Aurigene upon the U.S. Food and Drug Administration (FDA) acceptance of the CA-170 IND. Employee-related expenses increased over the prior year period primarily due to additional headcount to support the multiple programs. Research and development expenses were $15.7 million for the six months ended June 30, 2016 as compared to $10.7 million for the same period in 2015.

General and Administrative Expenses. General and administrative expenses remained unchanged at $3.4 million for the second quarter of 2016 as compared the second quarter of 2015. General and administrative expenses were $7.1 million for the six months ended June 30, 2016, as compared to $6.9 million for the same period in prior 2015.

Other expense, net was $0.6 million for the second quarter of 2016, as compared to $0.8 million for the same period in 2015. Other expense, net primarily consisted of $0.7 million and $0.8 million in interest expense for the quarters ended June 30, 2016 and 2015, respectively, related to the loan made by BioPharma-II (an investment fund managed by Pharmakon Advisors) to Curis Royalty (a wholly owned subsidiary of Curis). Other expense, net was $1.2 million and $1.6 million for the six months ended June 30, 2016 and 2015, respectively.

As of June 30, 2016, Curis’s cash, cash equivalents, marketable securities and investments totaled $61.7 million and there were approximately 129.5 million shares of common stock outstanding.

Second Quarter Operational Highlights

Precision oncology (CUDC-907: HDAC / PI3K inhibitor program):

In June 2016, updated data from the Phase 1 trial of CUDC-907 in 75 patients with relapsed/refractory lymphoma or multiple myeloma were presented at the European Hematology Association (EHA) (Free EHA Whitepaper)’s Annual Meeting. The updated assessment from a total of 31 of these patients with relapsed refractory DLBCL showed that among 21 response-evaluable patients with DLBCL, objective responses were reported in 9 patients, including 3 patients with complete responses. Additionally, a retrospective post-hoc analysis showed that among 6 response-evaluable DLBCL patients whose tumors were characterized with MYC alterations, 5 experienced objective responses, including 3 patients with complete responses. All 5 patients with MYC altered disease who experienced objective responses also had alterations in BCL-2, including 2 patients with BCL-2 gene translocations.

In June 2016, Curis presented the CUDC-907 Phase 2 trials-in-progress poster at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The presentation included the Phase 2 study’s design for investigating CUDC-907’s efficacy in patients with relapsed/refractory DLBCL with MYC alterations.
Immuno-oncology (CA-170: PD-L1 / VISTA antagonist program; Aurigene collaboration):

In June 2016, the Company filed an Investigational New Drug (IND) application with the U.S. FDA to initiate the Phase 1 trial of CA-170 for once-daily oral treatment of patients with advanced solid tumors or lymphoma. The FDA accepted the Company’s IND filing during the same month.

In June 2016, the Company initiated dosing of the first patient in the Phase 1 trial of CA-170.
Erivedge (partner: Roche/ Genentech):

In June 2016, Roche presented data from two trials of Erivedge at the ASCO (Free ASCO Whitepaper) Annual Meeting, highlighting that (1) the safety profile of Erivedge continues to be consistent with the previously reported safety profiles, and (2) intermittent dosing schedules may be an option for patients with multiple basal cell carcinomas to derive long term benefit from Erivedge treatment.
Upcoming Activities

Curis expects that it will make presentations at the following conferences through September 2016:

Baird’s Global Healthcare Conference on Sept 8-9, 2016 in New York City

BioCryst Reports Second Quarter 2016 Financial Results

On August 4, 2016 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported financial results for the second quarter ended June 30, 2016 (Press release, BioCryst Pharmaceuticalsa, AUG 4, 2016, View Source [SID:1234514234]).

"We continue to make progress, and have initiated subject screening to start the APeX-1 trial evaluating our once daily oral kallikrein inhibitor BCX7353 to prevent HAE attacks," said Jon P. Stonehouse, President & Chief Executive Officer. "Our goal remains to report out initial data by year end for this trial."

Second Quarter Financial Results
For the three months ended June 30, 2016, revenues decreased to $4.8 million from $25.8 million in the second quarter of 2015. The decrease was primarily due to the one time, partial recognition of a large upfront payment from Seqirus UK Limited (Seqirus) associated with the licensing of RAPIVAB (peramivir injection) in the second quarter of 2015, as well as lower collaborative revenue associated with BCX4430 development in the second quarter of 2016.

Research and Development (R&D) expenses for the second quarter of 2016 decreased to $14 .2 million from $16.5 million in the second quarter of 2015. This decrease was primarily due to lower development costs associated with the Company’s BCX4430 program.

General and administrative (G&A) expenses for the second quarter of 2016 decreased to $2.7 million compared to $3.5 million for the second quarter of 2015, due to a general reduction of administrative expenses throughout the Company during the second quarter of 2016, as compared to the second quarter of 2015.

Interest expense, which is primarily related to Company’s non-recourse notes payable, was $1.4 million in the second quarter of 2016 and $1.3 million in the second quarter of 2015. In addition, a $3.7 million mark-to-market loss on the Company’s foreign currency hedge was recognized in the second quarter of 2016, as compared to a $796,000 mark-to-market loss in the second quarter of 2015. These gains and losses result from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement. During the second quarters of 2016 and 2015, we also realized currency gains of $811,000 and $1.5 million, respectively, from the exercise of a U.S. Dollar/Japanese yen currency option within our foreign currency hedge.

The net loss for the second quarter of 2016 was $16.3 million, or a $0.22 net loss per share, compared to net income of $4.9 million, or $0.06 net income per fully diluted share, for the second quarter 2015.

Cash, cash equivalents and investments decreased to $64.3 million at June 30, 2016, as compared to $100.9 million at December 31, 2015. Net operating cash use for the second quarter of 2016 was $15.4 million, as compared to $12.0 million for the second quarter of 2015.

Year to Date Financial Results
For the six months ended June 30, 2016, total revenues decreased to $9.6 million from $32.7 million in the first half of 2015. The decrease in revenue resulted from the recognition of approximately $21.7 million of collaborative revenue in the second quarter of 2015 associated with the RAPIVAB out-licensing transaction with Seqirus in June 2015.

R&D expenses increased to $34.7 million in the first half of 2016 from $33.6 million in the first half of 2015. The increase in 2016 R&D expense, as compared to 2015, reflects increased spending in our RAPIVAB program, somewhat offset by decreased development activity in our BCX4430 program. The majority of R&D spending was associated with the Company’s HAE development program.

G&A expenses decreased to $5.9 million for the six months ended June 30, 2016 from $7.6 million for the six months ended June 30, 2015, due primarily to lower unrestricted grants awarded to HAE patient advocacy groups, as well as a general reduction of administrative expenses in the first half of 2016.

In the first half of 2016 and 2015, interest expense was $2.9 million and $2.6 million, respectively, and was primarily related to the Company’s non-recourse notes payable. A mark-to-market loss on our foreign currency hedge of $6.4 million was recognized in the first half of 2016, compared to a mark-to-market loss of $332,000 in the first half of 2015. These gains and losses result from periodic changes in the U.S. dollar/Japanese yen exchange rate and the related mark-to-market valuation of our underlying hedge arrangement. As noted above, we also realized currency gains of $811,000 and $1.5 million from the exercise of U.S. dollar/Japanese yen currency options during the first half of 2016 and 2015, respectively.

The net loss for the six months ended June 30, 2016 increased to $39.1 million, or $0.53 per share, from $10.3 million, or $0.14 per share for the same period last year.

Corporate Update & Outlook
The APeX-1 clinical trial of BCX7353 for prophylaxis of angioedema attacks in patients with HAE has received regulatory approval in Canada and several European countries, and patient screening has commenced. We expect initial data from APeX-1 to be available by year end 2016.

A clinical pharmacology study of several dosage formulations of avoralstat is nearing completion. Cohorts of healthy volunteers have received single doses ranging from 200 mg to 2000 mg of avoralstat in tablet or suspension formulations, with no clinically significant adverse events reported. While these dosing formulations have improved total avoralstat exposure (AUC) up to approximately five-fold compared to a 500 mg dose given as soft gel capsules, the plasma concentration-time profile has not met our objectives of twice-daily dosing with drug levels at or above the target range. For that reason, we have decided to stop further development of avoralstat.

A phase 1 first-in-human study of the broad-spectrum antiviral drug BCX4430 has been completed. Study drug was administered by i.m. injection to healthy volunteers. Single doses of BCX4430 ranging from 0.3 to 10 mg/kg were administered, and daily doses of 2.5 mg/kg to 10 mg/kg were administered for 7 days. Exposure to BCX4430 was dose-proportional. BCX4430 dosing was generally safe and well-tolerated, and there were no grade 3 or 4 adverse events.

On July 5, 2016, BioCryst announced that the National Institute of Allergy and Infectious Diseases (NIAID) has provided additional funding for efficacy studies of BCX4430 in non-human primates to further assess effective dose regimens. This funding represents an increase of $5.5 million for the development of BCX4430 as a treatment for hemorrhagic fever viruses. The NIAID contract value now totals $39.5 million, if all contract options are exercised. To date, approximately $35.4 million of funding has been awarded under the contract.

About APeX-1
APeX-1 is a two part, Phase 2, randomized, double-blind, placebo-controlled proof of concept and dose ranging trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of BCX7353 as a preventative treatment to eliminate or reduce the frequency of angioedema attacks in HAE patients. Up to a total of approximately 50 eligible subjects with HAE will be enrolled in the trial.

In part 1 of APeX-1, up to 36 subjects with HAE will be randomized in a 1:1 ratio to receive an oral dose of either 350 mg of BCX7353 once daily or placebo once daily for four weeks. An interim analysis will be conducted after the first 24 subjects have completed treatment through study day 28. If a robust treatment effect is observed at the interim analysis, Part 2 of the study will be initiated. In the event the treatment effect is not well characterized with 24 subjects, a total of up to approximately 36 subjects will be enrolled in part 1. The sample size in Part 1 was kept flexible to cover a range of response options that would achieve 90% power with an alpha of 0.05, based on reduction of attack rate of at least 70% on BCX7353, placebo response rate of approximately 30%, and standard deviation of approximately 0.45 attacks per week.

To characterize dose-response in part 2 of APeX-1, 14 additional subjects with HAE will be randomized to 250mg of BCX7353 once daily (n=6), 125mg of BCX7353 once daily (n=6) or placebo (n=2).

The primary efficacy endpoint of APeX-1 is the number of angioedema attacks; attack rate per week, counts of attacks, proportion of subjects with no attacks, and number of attack-free days will be analyzed. Efficacy analyses will be conducted for HAE attacks reported over the entire dosing interval (Days 1 through 28) and during the dosing period in which plasma concentrations of BCX7353 should be at steady-state conditions (Days 8 through 28). Secondary efficacy endpoints include severity and duration of angioedema attacks, and measures of health-related quality of life. Safety will be characterized through evaluation of adverse events and laboratory testing. Pharmacokinetics and pharmacodynamic effects will be assessed through measurement of plasma drug levels and kallikrein inhibition.

About BCX7353
Discovered by BioCryst, BCX7353 is a novel, once-daily, selective inhibitor of plasma kallikrein in development for the prevention of angioedema attacks in patients diagnosed with HAE. By inhibiting plasma kallikrein, BCX7353 suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients. BCX7353 has been generally safe and well tolerated in clinical pharmacology studies that have enrolled 117 healthy volunteers, 46 receiving single doses of up to 1000 mg, and 71 receiving once-daily doses of up to 500 mg for 7 days and 350 mg for 14 days. In the second week of study, approximately 4-5% of healthy volunteers administered daily doses of ‘7353 for at least 7 days developed a drug-related skin rash that resolved within a few days.

Financial Outlook for 2016
Based upon development plans and our awarded government contracts, BioCryst expects its 2016 net operating cash use to be in the range of $55 to $75 million, and its 2016 operating expenses to be in the range of $78 to $98 million. Our operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the Company’s stock, as well as by the vesting of the Company’s outstanding performance-based stock options.

AVEO Oncology Reports Second Quarter 2016 Financial Results and Provides Business Update

On August 4, 2016 AVEO Oncology (NASDAQ:AVEO) reported financial results for the second quarter ended June 30, 2016 (Press release, AVEO, AUG 4, 2016, View Source;p=RssLanding&cat=news&id=2192884 [SID:1234514233]).

"The second quarter of 2016 marked a defining moment for AVEO, with the initiation of TIVO-3, our Phase 3 pivotal study of tivozanib in refractory advanced renal cell cancer, and the closing of debt and equity financings to support our North American first- and third-line registration strategy for tivozanib as well as our planned PD-1 combination study," said Michael Bailey, president and chief executive officer. "We are very pleased with investigator support for TIVO-3 to date, and remain on track to complete enrollment in 2017 and see top-line data in the first quarter of 2018. We expect to achieve several milestones over the next 12 months, including the initiation of a tivozanib PD-1 combination study, a decision on approval for tivozanib in front-line RCC in Europe, meaningful progress in our partnered pipeline programs as well as a potential partnership for AV-353. Along with anticipated milestone payments from our partnered pipeline programs, we believe that our resources will allow us to fully fund our U.S. tivozanib development strategy through at least pivotal top-line data for TIVO-3 in the first quarter of 2018."

Recent Highlights

Dosing of First Patient in Pivotal Phase 3 TIVO-3 Study of Tivozanib in Renal Cell Carcinoma. In May 2016, AVEO announced that the first patient was dosed in the Company’s pivotal TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory advanced renal cell carcinoma (RCC). Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). The Phase 3 trial is expected to enroll approximately 322 patients with recurrent or metastatic RCC who have failed at least two prior regimens, including VEGFR-TKI therapy (other than sorafenib). Eligible patients may also have received checkpoint inhibitor therapy in earlier lines of treatment. Patients will be randomized 1:1 to receive either tivozanib or sorafenib, with no crossover between arms.

The primary endpoint of the study is progression free survival. Secondary endpoints include overall survival, overall response rate, and safety and tolerability. Top line readout of the study is currently projected for the first quarter of 2018. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support a first and third line indication for tivozanib in the U.S. A marketing authorization application seeking approval of tivozanib as a treatment for first line renal cell cancer is currently pending in Europe based on an application submitted by AVEO’s partner EUSA Pharma.
Closing of Private Placement and Amended Term Loan. In May 2016, AVEO announced the closing of a private placement of 17,642,482 units, each consisting of one share of common stock and a warrant to purchase one share of common stock, at a price of $0.965 per unit, for gross proceeds of approximately $17 million. The transaction was led by New Enterprise Associates and included New Leaf Venture Partners and Perceptive Advisors, among other institutional investors. Certain members of the Company’s management team and Board of Directors also participated in the financing. Piper Jaffray & Co. served as the exclusive placement agent for the financing.

The Company also announced that it entered into an amendment to its 2010 loan and security agreement with Hercules Capital, Inc. Pursuant to the loan amendment, the Company borrowed an additional $5.0 million from Hercules. If specified conditions are met, AVEO may borrow an additional tranche of $5.0 million from Hercules in the first half of 2017, and repayment of principal on AVEO’s loans may be deferred to begin in 2018.
Filing of Provisional Patent Applications for AV-353, a Notch 3-Specific Inhibitor Antibody for PAH. In May 2016, AVEO announced that it had filed provisional patent applications with the United States Patent and Trademark Office covering composition of matter claims for AV-353, the Company’s potent inhibitory antibody specific to Notch 3 for development in Pulmonary Arterial Hypertension (PAH). These patent applications are the second set of applications related to AV-353 and the Company’s Notch 3 antibody program. Current treatments in PAH focus only on controlling symptoms by avoiding vasoconstriction and increasing vasodilation of vessels and do not reverse the underlying cause of the disease. In contrast, with the results of a recently concluded research study supported by AVEO, AV-353 has generated a growing body of preclinical data that supports AV-353’s ability to potentially reverse the disease phenotype, which would represent a potential disease-modifying approach to treatment. Consistent with the Company’s focus on developing oncology therapeutics, AVEO is currently seeking an appropriate partner to develop and commercialize AV-353 worldwide in PAH.
Second Quarter 2016 Financial Highlights

AVEO ended Q2 2016 with $39.5 million in cash, cash equivalents and marketable securities as compared with $34.1 million at December 31, 2015. The increase was attributable to the net proceeds of our private placement of securities and additional borrowings under our existing loan and security agreement in the second quarter of 2016, net of the use of cash to fund operations during 2016.
Total collaboration revenue in Q2 2016 was approximately $0.2 million compared with $0.1 million Q2 2015. The increase was primarily due to $0.1 million in revenue recognized in the second quarter of 2016 in connection with the out-licensing agreement with EUSA, which was executed in December 2015.
Research and development expense was $5.6 million in Q2 2016 compared with $1.8 million for Q2 2015. The increase was primarily attributable to an increase in tivozanib clinical trial costs in connection with the preparation for, and conduct of, the TIVO-3 phase 3 trial in renal cell carcinoma that commenced enrollment and patient treatment in May 2016.
General and administrative expense was $1.7 million in Q2 2016 compared with $2.9 million for Q2 2015. The decrease was primarily the result of continued reduction of facilities and other operating expenses after completing our restructuring in the first quarter of 2015.
Net loss for Q2 2016 was $8.6 million, or a loss of $0.13 per basic and diluted share, compared with net loss of $5.5 million, or a loss of $0.10 per basic and diluted share for Q2 2015.
Financial Guidance

We believe that our $39.5 million in cash resources could allow us to fund our planned operations at least into the fourth quarter of 2017.

AVEO expects that its cash resources, its borrowing capacity under its amended loan agreement, together with certain anticipated operational milestone payments from its collaboration partners, could allow the Company to fund its U.S. tivozanib development strategy through at least pivotal Phase 3 TIVO-3 top-line data as well as a tivozanib-PD-1 inhibitor combination trial.

Array BioPharma Reports Financial Results For The Fourth Quarter And Full Year Of Fiscal 2016

On August 4, 2016 Array BioPharma Inc. (NASDAQ: ARRY), a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule cancer therapies, reported results for its fiscal fourth quarter and full year ended June 30, 2016 and provided an update on the progress of its key clinical development programs (Press release, Array BioPharma, AUG 4, 2016, View Source;p=RssLanding&cat=news&id=2192986 [SID:1234514231]).

Array BioPharma. (PRNewsFoto/Array BioPharma Inc.)
"The recent filing of an NDA for binimetinib in NRAS-mutant melanoma represents an important milestone for Array," said Ron Squarer, Array’s Chief Executive Officer. "We also look forward to announcing top-line results from our Phase 3 COLUMBUS trial in BRAF-mutant melanoma in the third quarter of 2016 and to advancing both the Phase 3 BEACON CRC trial in BRAF-mutant colorectal cancer and a new immuno-oncology Phase 1/2 trial of a CSF-1R inhibitor combined with a PD-1 inhibitor."

KEY PIPELINE UPDATES

Binimetinib (MEK162) and encorafenib (LGX818)

Novartis continues to substantially fund all ongoing trials with binimetinib and encorafenib that were active or planned as of the close of the Novartis Agreements in 2015, including the NEMO and COLUMBUS Phase 3 trials. Reimbursement revenue from Novartis was approximately $107.3 million for the previous 12 months, of which $33.4 million was recorded over the past quarter.

NEMO: Global Phase 3 trial of binimetinib versus dacarbazine in NRAS-mutant melanoma patients

Array submitted an NDA for binimetinib to the Food and Drug Administration (FDA) at the end of June 2016. Array is planning for an Oncologic Drugs Advisory Committee (ODAC) meeting as part of the regulatory review process. Array is also currently preparing for an Application Orientation Meeting (AOM) with the FDA in September 2016, which we expect will include a discussion of the NDA package including clinical risk / benefit.

Results from the NEMO trial were presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm; hazard ratio (HR) 0.62, [95% CI 0.47-0.80], p<0.001. In the pre-specified subset of patients who received prior treatment with immunotherapy, including ipilimumab, nivolumab or pembrolizumab, patients who received binimetinib experienced 5.5 months of median PFS (95% CI, 2.8–7.6), compared with 1.6 months for those receiving treatment with dacarbazine (95% CI, 1.5–2.8). While the results in the pre-specified sub-group of patients who had received prior treatment with immunotherapy are of interest, interpretation beyond overall consistency with the primary result should be made with care. Array anticipates that the primary consideration for marketing approval will be the results for the primary endpoint of the trial.

In addition to improving PFS, binimetinib also demonstrated significant improvement in overall response rate (ORR) and disease control rate (DCR). While there was no statistically significant difference demonstrated in overall survival, the median overall survival (mOS) favored the binimetinib arm.

Confirmed ORR was 15 percent (95% CI, 11-20 percent) in patients receiving binimetinib vs. 7 percent (95% CI, 3-13 percent) in patients receiving dacarbazine.
DCR for patients receiving binimetinib was 58 percent (95% CI, 52-64 percent) vs. 25 percent (95% CI, 18-33 percent) for patients receiving dacarbazine.
mOS was estimated at 11.0 months in patients receiving binimetinib vs. 10.1 months for patients treated with dacarbazine [(HR) = 1.0 (95% CI 0.75-1.33), p=0.499].
Under the NEMO protocol, and in accordance with accepted statistical practice, the subgroup analyses of overall survival (OS) are formally conducted only if the key secondary endpoint of OS reached statistical significance.

Binimetinib was generally well-tolerated and the adverse events (AEs) reported were consistent with previous results in NRAS-mutant melanoma patients. Grade 3/4 AEs reported in greater than or equal to 5 percent of patients receiving binimetinib included increased creatine phosphokinase (CPK) and hypertension.

Activating NRAS mutations are present in up to 20 percent of patients with metastatic melanoma, and are a poor prognostic indicator for these patients. Treatment options for this population remain limited beyond immunotherapy, and these patients face poor clinical outcomes and high mortality.

COLUMBUS: Global Phase 3 trial of binimetinib plus encorafenib versus vemurafenib in BRAF-mutant melanoma patients

Array expects COLUMBUS top-line results during the third quarter of 2016.

Activating BRAF mutations are present in approximately 50 percent of patients with metastatic melanoma. In two separate Phase 1/2 trials in this patient population, binimetinib plus encorafenib demonstrated encouraging clinical activity and an attractive tolerability profile, including low incidence of pyrexia and little to no incidence of rash or photosensitivity. Patients treated in two Phase 3 trials of dabrafenib plus trametinib (COMBI-d and COMBI-v) experienced greater than 50 percent incidence of pyrexia (fever), while in a large, randomized trial of vemurafenib and cobimetinib (coBRIM) nearly 50 percent of patients experienced photosensitivity reactions. Of the patients who experienced pyrexia on COMBI-d and COMBI-v, one-half reported three or more events, and at least half required dose modifications, including interruptions, reductions or discontinuation as a result of their pyrexia. Of the patients who experienced photosensitivity on coBRIM, the median duration of photosensitivity was three months, with some patients experiencing durations as long as 14 months. Only 63 percent of patients on coBRIM with photosensitivity reactions experienced resolution while on study.

BEACON CRC: Global Phase 3 trial of binimetinib, encorafenib and Erbitux (cetuximab) versus Erbitux in BRAF-mutant colorectal cancer (CRC) patients

During the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting, Array, Pierre Fabre, and Merck KGaA, Darmstadt, Germany, jointly announced the initiation of BEACON CRC (Binimetinib, Encorafenib And Cetuximab Combined to treat BRAF-mutant ColoRectal Cancer), a pivotal Phase 3 global clinical trial, assessing the efficacy of binimetinib, encorafenib and Erbitux compared to Erbitux and irinotecan-based therapy in patients with BRAF-mutant CRC.

BEACON CRC is a randomized, open-label, global study evaluating the efficacy and safety of binimetinib, encorafenib and Erbitux in patients with BRAF-mutant metastatic CRC who have previously received first-or second-line systemic therapy. The study includes a safety lead-in with approximately 30 patients. With appropriate results from the lead-in, approximately 615 patients are expected to be randomized 1:1:1 to receive triplet therapy (binimetinib, encorafenib and Erbitux), doublet therapy (encorafenib and Erbitux) or the control arm (irinotecan-based therapy and Erbitux).

The primary endpoint of the trial is OS of the triplet therapy compared to the control arm. Secondary endpoints address efficacy of the doublet therapy compared to the control arm, and the triplet therapy compared to the doublet therapy. Other secondary endpoints include PFS, objective ORR, duration of response, safety and tolerability. Health related quality of life data will also be assessed.

Array will act as the global sponsor of the study. Pierre Fabre licensed commercial rights to binimetinib and encorafenib for Europe and other global markets from Array in December 2015. As part of this collaboration, Pierre Fabre has elected to co-fund 40 percent of the cost of the BEACON CRC trial. Merck KGaA, Darmstadt, Germany, is the owner of Erbitux outside of the United States and Canada, and will supply Erbitux to all trial sites in those geographies as part of the collaboration. If successful, the results would support regulatory submissions for all three parties.

Array also announced updated results from a Phase 2 study of the combination of encorafenib and cetuximab, with or without alpelisib, a selective PI3K alpha inhibitor, in patients with advanced BRAF-mutant CRC at the 2016 ASCO (Free ASCO Whitepaper) meeting. Data from this study suggest that mOS for these patients may exceed one year, which is more than double several historical published benchmarks for this population.

In the Phase 2 study, 102 patients with BRAF-mutant CRC who had progressed after one or more prior therapies were randomized to receive the doublet regimen of encorafenib and cetuximab (ENCO 200 mg PO QD and CETUX per label; n=50) or the triplet regimen of encorafenib, cetuximab and alpelisib (ENCO, CETUX and ALP 300 mg PO QD; n=52). The Phase 2 analysis for these treatment regimens demonstrated promising clinical activity in patients:

Median OS was 12.4 and 13.1 months for the doublet and alpelisib-containing triplet regimens, respectively.
Median PFS was 4.2 and 5.4 months for the doublet and alpelisib-containing triplet regimens, respectively.
ORR was 22 percent and 27 percent for the doublet and alpelisib-containing triplet regimens, respectively.
Grade 3 or 4 AEs occurring in greater than 10 percent of patients included anemia, hyperglycemia and increased lipase.
Several historical published median PFS and median OS results after first-line treatment range from 1.8 to 2.5 months and four to six months, respectively, and published ORR from various studies in this population range between six percent to eight percent. As alpelisib added toxicity with only marginal additional activity, the BEACON CRC trial utilizes binimetinib, a MEK inhibitor, in the triplet arm.

Colorectal cancer is the third most common cancer among men and women in the United States, with more than 134,000 new cases and nearly 50,000 deaths from the disease projected in 2016. In the United States, BRAF mutations occur in 8 to 15 percent of patients with colorectal cancer and represent a poor prognosis for these patients.

ARRY-382

Phase 1/2 dose escalation study initiated with ARRY-382, a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, in combination with pembrolizumab, a PD-1 antibody, for the treatment of patients with advanced solid tumors

In July 2016, Array initiated a Phase 1/2 dose escalation immuno-oncology trial of ARRY-382 in combination with pembrolizumab (Keytruda), a Programmed Cell Death Receptor 1 (PD-1) antibody, in patients with advanced solid tumors. ARRY-382 is a wholly-owned, potent, highly selective, small-molecule inhibitor of CSF-1R kinase activity.

The study will enroll up to 18 patients with selected advanced solid tumors to determine the maximum tolerated dose and/or recommended Phase 2 dose of the combination. In addition, the safety profile, pharmacodynamic effects, and preliminary assessment of activity of the combination will be assessed. With appropriate results, Array has the option to advance the combination into expansion cohorts of patients with metastatic melanoma or advanced non-small cell lung cancer (NSCLC).

Results from a prior Phase 1 study designed to assess the safety, pharmacokinetics and pharmacodynamics of ARRY-382 for treating patients with cancer have been presented and a dose and schedule that demonstrates target engagement based on multiple pharmacodynamic biomarkers was identified for further study.

With this new combination study, Array is strengthening its position in the immuno-oncology field. Earlier this year, Array initiated an immuno-oncology research collaboration with the Dana-Farber Cancer Institute that Array believes has broad potential applicability to its drug discovery efforts.

ARRY-797 (ARRY-371797)

Phase 2 trial ongoing 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. Results will be presented at the European Society of Cardiology on August 30, 2016. By age 45, approximately 70 percent of patients with LMNA A/C-related DCM will have died; suffered a major cardiac event; or will have undergone a heart transplant. Array has presented a qualitative summary of the Phase 2 study. The primary endpoint of the study is mean change in the six-minute walk test (6MWT) at 12 weeks relative to the baseline. ARRY-797 exceeded benchmarks set by a number of recently-approved drugs for rare diseases on the basis of the 6MWT as a primary endpoint. Secondary endpoints in the ARRY-797 trial, including changes in N-Terminal pro-Brain-derived Natriuretic Peptide (NT-proBNP, a serum biomarker of heart failure severity), and patient reported outcomes, are directionally consistent with the primary endpoint. Data for patients followed over a 48-week period suggest a durable effect. Taken together, the data to date suggest a path forward for this program, and Array has met with regulators to discuss the design of a study that could be the basis for marketing approval.

Selumetinib (partnered with AstraZeneca)

Registration trials advancing in NSCLC (SELECT-1), thyroid cancer (ASTRA) and neurofibromatosis type 1

AstraZeneca expects top-line results from SELECT-1 in the second half of 2016 and projects a regulatory filing of selumetinib in NSCLC in the first half of 2017. AstraZeneca continues to advance selumetinib in three registration trials: SELECT-1 in patients with KRAS-mutant non-small cell lung cancer (NSCLC); a registration trial in patients with neurofibromatosis type 1; and ASTRA in patients with differentiated thyroid cancer.

SELECT-1 is a 500-patient randomized, double-blind, placebo-controlled study that was designed to evaluate the safety and efficacy of selumetinib plus docetaxel as a second-line therapy in locally advanced or metastatic KRAS-mutant NSCLC. KRAS mutations are among the most common mutations in NSCLC, present in approximately 25 percent of these patients. The study is designed to evaluate PFS as the primary endpoint, and a key secondary endpoint is OS. AstraZeneca’s decision to progress selumetinib to Phase 3 in NSCLC followed the results from a randomized Phase 2 study evaluating the combination of selumetinib with docetaxel against docetaxel alone in KRAS-mutation positive NSCLC. This study demonstrated response rates of 37.2% vs 0% (p<0.0001), and a statistically significant improvement in PFS of 5.3 vs 2.1 months (HR 0.58, p<0.014).

FINANCIAL HIGHLIGHTS

Cash, cash equivalents and marketable securities were approximately $111 million and accounts receivable were approximately $39.3 million as of June 30, 2016. Accounts receivable primarily consist of receivables expected to be paid by Novartis within three months. In March 2015, binimetinib and encorafenib became wholly-owned assets of Array, which prompted changes to the classification of revenue and expenses for the programs. The new expense classifications were included in the financial results for the fourth quarter of fiscal 2015. Beginning in the first quarter of fiscal 2016, Array reports revenue from the Novartis reimbursements under its agreements with Novartis for binimetinib and encorfenib as a separate line item called "reimbursement revenue." The net earnings (or loss) per share described below are diluted net earnings (or loss) per share.

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

Revenue for the fourth quarter of fiscal 2016 was $43.2 million, compared to $43.0 million for the prior sequential quarter.
Cost of partnered programs for the fourth quarter of fiscal 2016 was $5.4 million, compared to $5.8 million for the prior quarter.
Research and development expense was $49.5 million, compared to $48.8 million in the prior quarter.
Net loss for the fourth quarter was $25.0 million, or ($0.17) per share, and was $22.7 million, or ($0.16) per share in the prior quarter. The increase in net loss was primarily due to the initiation of the BEACON CRC trial.
Fourth Quarter of Fiscal 2016 Compared to Fourth Quarter of Fiscal 2015 (Prior Year Comparison)

Revenue for the fourth quarter of fiscal 2016 increased by $30.9 million compared to the same quarter of fiscal 2015, primarily due to reimbursement revenue from Novartis.
Cost of partnered programs decreased by $1.5 million compared to the fourth 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 by $30.9 million compared to the fourth quarter of fiscal 2015 due to the change in categorization of binimetinib costs, as well as new investment in encorafenib.
Net loss for the fourth quarter of fiscal 2016 was $25.0 million, or ($0.17) per share, and was $12.7 million, or ($0.09) per share, for the same quarter in fiscal 2015.
Full Year of Fiscal 2016 Compared to Full Year of Fiscal 2015 (Prior Year Comparison)

Revenue was $137.9 million for the fiscal year ended June 30, 2016, compared to $51.9 million for the same period in fiscal 2015.
Net loss for the fiscal year ended June 30, 2016, was $92.8 million, or ($0.65) per share, compared to a net income of $9.4 million, or $0.07 per share, in the comparable prior year period.
The fiscal year ended 2015 included a one-time $80.0 million net gain on the binimetinib and encorafenib agreements.
Net cash used in operating activities for the fiscal year ended June 30, 2016 was $70.1 million.
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