1stOncology™: Cancer Intelligence Service – Page 15647 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Pacira Pharmaceuticals, Inc. Reports Second Quarter 2016 Financial Results

On August 4, 2016 Pacira Pharmaceuticals, Inc. (NASDAQ:PCRX) reported updates on EXPAREL (bupivacaine liposome injectable suspension) for postsurgical pain in the United States and announced consolidated financial results for the second quarter ended June 30, 2016 (Press release, Pacira Pharmaceuticals, AUG 4, 2016, View Source;p=RssLanding&cat=news&id=2192934 [SID:1234514287]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"The second quarter marked another period of double-digit, year-over-year revenue growth as we advanced multiple initiatives to support EXPAREL in the latter half of this year and into 2017," said Dave Stack, Chief Executive Officer and Chairman of Pacira. "Our aggressive investments in patient outreach and clinical development, as well as commercial and educational programs, are progressing as planned. For the rest of this year, we look forward to continuing the strong progress we’ve made with the Phase 4 randomized controlled trials in strategic orthopedic surgeries, Phase 3 nerve block studies, enhanced recovery protocols in soft tissue procedures and data presentations on bundled payments. We also anticipate increasing our public relations and advocacy efforts to bring attention to addressing the opioid epidemic by providing an alternative to opioids in the acute postsurgical setting, where epidemic often starts."

Recent Highlights

Choices Matter Launches in Response to New Research Showing Opioid Addiction and Dependence After Surgery is Significantly Higher than Previously Known: Although the national focus of research has primarily been on opioid addiction as a result of their use to treat chronic pain, new research shows that even prescribing opioids for short-term postsurgical pain can put patients at serious risk, with one in ten patients surveyed indicating they’ve become addicted to or dependent on opioids after being exposed to these powerful medications following an operation. On August 1, Pacira launched the Choices Matter campaign to foster surgeon-patient dialogue and educate patients about their non-opioid options, empowering them to play an active role in the decision-making process related to their postsurgical pain management. The American Society for Enhanced Recovery and former star volleyball player, Gabrielle Reece, whose recent knee replacement surgery has made this issue personal, have joined the campaign.

Preparations in Support of Oral Surgery Launch are Underway: Pacira remains on track for the launch of EXPAREL in oral surgery at the American Association of Oral and Maxillofacial Surgeons (AAOMS) annual meeting in September, where the company will present the results of the study in third molar, or "wisdom teeth," procedures. EXPAREL will provide an alternative to opioids for targeted oral and maxillofacial surgeries. In fact, a recent study in full arch surgery therapy (FAST) dental implant procedures showed that patients receiving EXPAREL experienced significantly less cumulative pain compared to patients receiving standard of care. With this launch, Pacira will also introduce a 10 mL vial and 4 vial package configuration of EXPAREL to the oral surgery marketplace.

Data Continue to Demonstrate Benefits of EXPAREL versus Bupivacaine Across Multiple Surgical Specialties, Including Soft Tissue Procedures: A study was recently published in Anaesthesia assessing patients who received ultrasound-guided transversus abdominis plane (TAP) blocks with EXPAREL versus non-liposomal bupivacaine for postsurgical pain control after undergoing laparoscopic hand-assisted donor nephrectomy. Patients who received EXPAREL experienced a significant decrease in maximal pain scores 24-48 and 48-72 hours after injection, as well as a significant reduction in opioid use 48-72 hours following injection. In July, the Foundation for Women’s Cancer hosted a webinar highlighting the importance of pain management as part of an enhanced recovery strategy for gynecologic oncology surgeries. Dr. Sean Dowdy presented data demonstrating that patients who received an enhanced recovery protocol (ERP) with EXPAREL for pain control for complex cytoreduction achieved a 90% reduction in opioid requirements compared to conservative management.
Second Quarter 2016 Financial Results

EXPAREL net product sales were $65.8 million in the second quarter of 2016, a 15% increase over the $57.0 million reported for the second quarter of 2015.

Total revenues were $69.6 million in the second quarter of 2016, an 18% increase over the $59.1 million reported for the second quarter of 2015.

Total operating expenses were $76.1 million in the second quarter of 2016, compared to $57.3 million in the second quarter of 2015.

GAAP net loss was $8.0 million, or $(0.21) per share (basic and diluted), in the second quarter, compared to GAAP net income of less than $0.1 million, or $0.00 per share (basic and diluted), in the second quarter of 2015.

Non-GAAP net income was $7.9 million, or $0.21 per share (basic) and $0.19 per share (diluted), in the second quarter of 2016, compared to non-GAAP net income of $8.4 million, or $0.23 per share (basic) and $0.20 per share (diluted), in the second quarter of 2015.

Pacira ended the second quarter of 2016 with cash, cash equivalents and short-term investments ("cash") of $162.7 million.

Pacira had 37.2 million basic weighted average shares of common stock outstanding in the second quarter of 2016.

For non-GAAP measures, Pacira had 40.8 million diluted weighted average shares of common stock outstanding in the second quarter of 2016.
2016 Outlook

Pacira updates full year 2016 financial guidance as follows:

EXPAREL net product sales of $270 million to $280 million.

Non-GAAP gross margins of 70% to 73%.

Non-GAAP research and development (R&D) expense of $60 million to $70 million.

Non-GAAP selling, general and administrative (SG&A) expense of $125 million to $135 million.

Stock-based compensation of $30 million to $35 million.
Today’s Conference Call and Webcast Reminder

The Pacira management team will host a conference call to discuss the company’s financial results and recent developments today, Thursday, August 4, 2016, at 9 a.m. ET. The call can be accessed by dialing 1-877-845-0779 (domestic) or 1-720-545-0035 (international) ten minutes prior to the start of the call and providing the Conference ID 12857671.

A replay of the call will be available approximately two hours after the completion of the call and can be accessed by dialing 1-855-859-2056 (domestic) or 1-404-537-3406 (international) and providing the Conference ID12857671. The replay of the call will be available for two weeks from the date of the live call.

The live, listen-only webcast of the conference call can also be accessed by visiting the "Investors & Media" section of the company’s website at investor.pacira.com. A replay of the webcast will be archived on the Pacira website for two weeks following the call.

Non-GAAP Financial Information

This press release contains financial measures that do not comply with U.S. generally accepted accounting principles (GAAP), such as non-GAAP net income, non-GAAP cost of goods sold, non-GAAP gross margins, non-GAAP research and development (R&D) and non-GAAP selling, general and administrative (SG&A) expenses, because such measures exclude stock-based compensation, amortization of debt discount, loss on extinguishment of debt and a termination fee with CrossLink BioScience, LLC. These measures supplement our financial results prepared in accordance with GAAP. Pacira management uses these measures to better analyze its financial results, estimate its future cost of goods sold, gross margins, R&D and SG&A outlook for 2016 and to help make managerial decisions. In management’s opinion, these non-GAAP measures are useful to investors and other users of our financial statements by providing greater transparency into the operating performance at Pacira and the company’s future outlook. Such measures should not be deemed to be an alternative to GAAP requirements or a measure of liquidity for Pacira. Non-GAAP net income measures are also unlikely to be comparable with non-GAAP disclosures released by other companies. See the tables below for a reconciliation of non-GAAP net income to GAAP net income (loss), and a reconciliation of our non-GAAP to GAAP 2016 financial guidance for gross margins, R&D and SG&A.

Corvus Pharmaceuticals Announces Second Quarter Financial Results and Provides Business Update

On August 4, 2016 Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), reported financial results for the second quarter and six months ended June 30, 2016 and provided a business update (Press release, Corvus Pharmaceuticals, AUG 4, 2016, View Source;p=RssLanding&cat=news&id=2193256 [SID:1234514283]).

"We are making good progress with our product candidates," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "Enrollment in the dose selection stage of our Phase 1/1b trial with our lead product candidate, CPI-444, is continuing on track and as of today we have opened 18 sites in the U.S., Canada and Australia. Patients have been dosed in each of the three single agent cohorts and in the cohort evaluating CPI-444 in combination with Genentech’s TECENTRIQ (atezolizumab).

"We also initiated IND-enabling studies with our humanized anti-CD73 antibody, an adenosine production inhibitor, in anticipation of commencing a Phase 1 trial in late 2017. Additionally, we selected a lead candidate for our ITK inhibitor program and expect to start IND-enabling studies with a Phase 1 trial anticipated in late 2017.

"To date, our successful execution of a strategy based on in-licensing product opportunities and developing products from our internal R&D efforts has led to a robust pipeline of four programs. During the quarter, we continued to build upon this strategy and expertise with the recently announced addition of Dr. Jason Coloma, who joins us from Roche as our Chief Business Officer, and who adds further depth to our team," concluded Dr. Miller.

SUMMARIZED HIGHLIGHTS OF THE QUARTER AND SUBSEQUENT WEEKS INCLUDED:

Ongoing enrollment in the dose selection stage of Corvus’ Phase 1/1b trial with CPI-444 with patients dosed in each of the four cohorts; three of which are single agent and one that is in combination with Genentech’s TECENTRIQ
Presented at the Rational Combinations meeting in June preliminary biomarker and research data indicating CPI-444’s ability to block the peripheral lymphocyte adenosine A2A receptor. These data confirmed that dosing leads to high levels of A2A receptor occupancy by the drug. In addition, observations of an increase in activated immune cells in blood in some treated patients receiving single agent and combination therapy were reported. The presentation also included preclinical models demonstrating the foundational strategy for CPI-444 with single agent activity and synergy shown in several tumor models with various checkpoint inhibitors
Received notice of the acceptance of three abstracts for the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting to be held October 7-11
Announced the hiring of Dr. Jason Coloma from Roche to the newly created post of Chief Business Officer
Initiated IND-enabling studies using Corvus’ humanized anti-CD73 antibody with a Phase 1 trial planned for late 2017
Selected a lead ITK inhibitor drug candidate for IND enabling studies with plans to initiate a Phase 1 in late 2017
SECOND QUARTER 2016 FINANCIAL RESULTS

At June 30, 2016, Corvus had cash, cash equivalents and marketable securities totaling $152.2 million, which included the underwriter’s decision to exercise its over-allotment option to purchase 502,618 shares of Corvus’ common stock following its IPO, and which resulted in net proceeds to the Company of $7.0 million. This compared to cash, cash equivalents and marketable securities of $94.4 million at December 31, 2015.

Research and development expenses for the three months ended June 30, 2016 totaled $7.1 million, up from $2.0 million for the prior period, primarily due to an increase of $1.4 million in personnel and related costs associated with higher headcount, an increase of $2.1 million in outside costs for the Phase 1/1b clinical trial for CPI-444, and an increase of $1.1 million in outside costs associated with other clinical development programs.

General and administrative expenses for the three months ended June 30, 2016 increased to $1.7 million, from $0.3 million for the prior period, primarily due to an increase of $0.9 million in personnel and associated costs, and $0.3 million in costs associated with operating as a public company.

The net loss for the three months ended June 30, 2016 was $8.6 million, compared with a net loss of $20.2 million, for same period in 2015. The 2015 net loss included $17.9 million associated with a non- cash change in the fair value of the company’s convertible preferred stock liability. Total stock compensation expense for the three months ended June 30, 2016 was $1.1 million, compared to negligible stock compensation expense in the prior year period.

First-In-Human Trials using Non-Viral Sleeping Beauty System to Express CD19-Specific CAR in T cells Published in Journal of Clinical Investigation

On August 4, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new immunotherapies, reported the publication of data highlighting the benefits of using the non-viral Sleeping Beauty (SB) system to genetically modify T-cells to express a chimeric antigen receptor (CAR) for use against leukemias and lymphomas (Press release, Ziopharm, AUG 4, 2016, View Source [SID:1234514282]). The article, titled "Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells," was published in the Journal of Clinical Investigation (doi:10.1172/JCI86721), and is available online here.

In the paper, 26 patients with multiply relapsed B-lineage acute lymphoblastic leukemia (ALL, n=17) or B-cell non-Hodgkin lymphoma, (NHL, n=9) were enrolled in two investigator-initiated clinical trials at the University of Texas MD Anderson Cancer Center infusing SB-modified T cells after autologous (n=7) or allogeneic (n=19) hematopoietic stem-cell transplantation (HSCT).

Autologous CAR-T: Seven patients with advanced NHL were treated with autologous HSCT followed by administration of patient-derived CAR T cells. Six of the seven patients remain in complete remission (CR) and the 30-month progression-free survival (PFS) and overall survival (OS) rates were 83.3% and 100%, respectively.
Allogeneic CAR-T: Nineteen patients (ALL n=17, NHL n=2) received donor-derived CAR T cells. The patients had advanced disease at the time of HSCT and CAR T cells were administered without additional lymphodepletion. Eleven of 19 patients remain in remission with 1-year PFS and OS rates of 53% and 63%, respectively.
HLA partially-matched allogeneic CAR-T: When the subset of allogeneic recipients of HSCT receiving haplo-identical CAR T cells were examined, eight patients had 1-year PFS and OS rates of 75% and 100%, respectively.
SB-mediated gene transfer and stimulation resulted in large ex vivo expansion of T cells while retaining CAR expression and without integration hotspots. Autologous and allogeneic T cells survived after infusion an average of 201 and 51 days, respectively. No unexpected acute infusion or delayed toxicities were noted in the autologous or allogeneic recipients. Mild elevations in cytokines were observed without cytokine storm.

Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM, states: "By following these patients over an extended duration, as we do in these studies, we can better understand the added benefit of CAR-T over HSCT alone. Although the primary objective of these trials was not to establish efficacy, the recipients’ outcomes are encouraging with apparent doubling of survivals compared to historical controls. We are encouraged by these clinical data and look forward to results from our Phase 1 study infusing our next generation CD19-specific CAR T cells in patients with advanced lymphoid malignancies."

Supported by results from two Phase I clinical studies conducted by investigators at MD Anderson Cancer Center, the publication describes how the use of the SB transposon/transposase platform could reduce the costs and complexity associated with recombinant viral vector-based immunotherapy. Additionally, by infusing a CD19-specific CAR T cells to target minimal residual disease after autologous and allogeneic HSCT, the SB system may improve tolerability by avoiding cytokine storm.

"The use of the non-viral Sleeping Beauty platform provides us with leverage to both decrease the cost of modifying T cells and reduce the T-cell manufacturing steps requiring GMP," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "As we continue to advance Sleeping Beauty engineered designs, ZIOPHARM benefits from both viral and non-viral approaches within CAR-T, while focusing efforts on non-viral gene delivery for TCR given its unique ability to enable personalized therapies for patients with solid tumors."

Juno Therapeutics Reports Second Quarter 2016 Financial Results

On August 4, 2016 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported financial results and business highlights for the second quarter 2016 (Press release, Juno, AUG 4, 2016, View Source;p=RssLanding&cat=news&id=2193215 [SID:1234514279]).

"The JCAR015 Phase II ROCKET trial is open again after we amended the protocol to return to a cyclophosphamide-only preconditioning regimen. If the ROCKET data are in the range of the Phase I results, where most patients were treated using this preconditioning regimen, we will have the opportunity to change the standard of care and offer improved hope for adult patients with relapsed or refractory ALL," said Hans Bishop, Juno’s President and Chief Executive Officer. "Additionally, we continue to enroll patients in our JCAR017 trial. We are encouraged that JCAR017, the backbone of our CD19 franchise, will change the standard of care again across a range of B cell malignancies with approvals projected to occur as early as 2018."
Second Quarter 2016 and Recent Corporate Highlights
Clinical Update:

CD19 Portfolio:

JCAR015
Announced the removal on July 12, 2016 by the U.S. FDA of a clinical hold that the agency had placed on the Phase II ROCKET trial on July 6, 2016. The ROCKET trial continues using JCAR015 with cyclophosphamide (cy) preconditioning alone. Juno’s trials and plans for its other CD19-directed CAR T cell product candidates, including JCAR017, were not affected.

Announced interim results, as of May 19, 2016, in Memorial Sloan Kettering Cancer Center’s (MSK) Phase I trial of JCAR015 in adult relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) patients:
Complete remission was observed in 23/30 (77%) patients with morphologic disease and in 18/20 (90%) patients with minimal disease. In patients who achieved a complete remission and had adequate evaluation for minimal residual disease by flow cytometry or polymerase chain reaction, complete molecular remission (CmR) was observed in 19/21 (90%) patients with morphologic disease and in 14/18 (78%) patients with minimal disease.

Median overall survival (OS) for patients with minimal disease treated with JCAR015 had not been reached yet, and that for morphologic patients treated with JCAR015 was 9 months; median OS follow-up for all patients was 13 months with 40% of patients alive at two years.

Durable responses and survival observed in patients who received JCAR015 were comparable between groups that received a subsequent stem cell transplant and those that did not.

Severe cytokine release syndrome (sCRS) was observed in 14/51 (27%) patients and severe neurotoxicity was observed in 15/51 (29%) patients. For patients with minimal disease, 1/20 (5%) patients experienced sCRS and 4/20 (20%) patients had severe neurotoxicity.

JCAR017
Announced Phase I non-Hodgkin lymphoma (NHL) preliminary efficacy and safety data for the ongoing trial. As of early July, 13 patients were evaluable for safety. Two, or 15%, experienced severe neurotoxicity and no patients experienced sCRS. There are early signs of efficacy with an overall response rate of eight out of ten efficacy-evaluable patients, or 80%, and a complete response rate of seven out of ten, or 70%. We plan to update results with more patients and durability data at a future scientific meeting.

Announced interim results, as of May 17, 2016, from Seattle Children’s ongoing Phase I/II study of JCAR017 in pediatric and young adults with r/r ALL (n=42) demonstrating 39/42 (93%) patients experienced a complete remission, all of which were a CmR by flow cytometry. In patients who received fludarabine/cyclophosphamide (flu/cy) preconditioning followed by JCAR017, 14/14 (100%) achieved a complete remission and a CmR. sCRS was observed in 10/42 (24%) patients and severe neurotoxicity was observed in 10/42 (24%) patients. The rates of sCRS and severe neurotoxicity were similar in the flu/cy and cy cohorts of this trial.
JCAR014 – Announced interim results, as of May 18, 2016, from Fred Hutchinson Cancer Research Center’s (FHCRC) ongoing Phase I/II study of JCAR014 in adults with advanced B cell malignancies:
In efficacy-evaluable ALL patients (n=34), complete remission was reported in 34/34 (100%) patients and a CmR as measured by flow cytometry was achieved in 32/34 (94%) patients. In the cohort that received flu/cy preconditioning followed by JCAR014, 22/22 (100%) of the efficacy-evaluable patients achieved a complete remission, all of which were a CmR. Median disease free survival (DFS) and OS have not yet been reached in this cohort of patients, with follow-up for up to 18 months. sCRS was observed in 14/36 (39%) patients and severe neurotoxicity was observed in 14/36 (39%) patients.

In patients with multiple NHL histologies (n=20), predominantly diffuse large B-cell lymphoma, who received flu/cy preconditioning followed by JCAR014 dose level 2 (2×106/kg), 16/20 (80%) had an overall response (OR), of which 10/20 (50%) experienced a complete response (CR). CRs continued in 70% of patients, ranging from 3 to 11+ months. sCRS was observed in 2/20 (10%) patients and severe neurotoxicity was observed in 2/20 (10%) patients. Notably, 16/20 (80%) patients treated with flu/cy preconditioning followed by JCAR014 dose level 2 were treated in the outpatient setting, and 6/20 (30%) did not require hospitalization during the first 30 days of treatment.

A total of 13 high-risk chronic lymphocytic leukemia (CLL) patients (complex karyotype, del17p, ibrutinib-refractory, ibrutinib-intolerant) received JCAR014 and either non-flu/cy (n=2) or flu/cy (n=11) preconditioning. In the flu/cy patients, the OR rate was 10/11 (91%) patients, of which 5/11 (45%) patients achieved CR. CRs were ongoing in 100% of these five patients with a range of 3 to 19+ months. sCRS was observed in 3/13 (23%) patients and severe neurotoxicity was observed in 3/13 (23%) patients.
JCAR018 – Investigators presented interim data, from the ongoing Phase I study in pediatric and young adult r/r ALL patients at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2016 (AACR 2016), showing all three patients at dose level 2 (1 x 106 cells/kg) achieved a complete remission and CmR as measured by flow cytometry. These patients remained in complete remission with follow-up ranging from 3 to 6 months. Limited cytokine release syndrome and no severe neurotoxicity was seen at dose level 2. Dose limiting toxicity was observed at higher doses, so dosing will continue at dose level 2 (1 x 106 cells/kg).

JTCR016 – In the first three solid organ tumor patients treated on the trial, all with mesothelioma, preliminary data, as of early April, presented at AACR (Free AACR Whitepaper) 2016 showed one patient with an ongoing partial response to the WT-1 TCR. The clinical activity appeared to correlate with the pharmacokinetics of the engineered T cells, as the patient with the partial response had the best T cell expansion and persistence. JTCR016 was generally well-tolerated in these three refractory mesothelioma patients, with no evidence of sCRS or severe neurotoxicity.

Corporate News:
Celgene Corporation exercised its option to develop and commercialize CAR product candidates from Juno’s CD19 program outside of North America and China. With the exercise of this option, Celgene paid Juno a fee of $50.0 million and the companies will now generally share worldwide research and development expenses for CAR product candidates in the CD19 program. Celgene has commercial rights outside of North America and China, and will pay Juno a royalty at a percentage in the mid-teens on any future net sales in Celgene’s territories of CAR therapeutic products developed through the CD19 program. Juno retains commercialization rights in North America and China.

Juno entered into an exclusive license agreement with MSK and Eureka Therapeutics, Inc. for a novel, fully-human binding domain targeting B-cell maturation antigen (BCMA), along with antibodies against two additional undisclosed multiple myeloma targets to be used for the potential development and commercialization of CAR cell therapies for patients with multiple myeloma. MSK and Eureka Therapeutics are eligible to receive an undisclosed upfront payment, additional payments upon the achievement of undisclosed clinical, regulatory, and commercial milestones, and royalties on net sales. The parties expect the BCMA CAR to enter human testing as early as the first half of 2017.

Juno acquired RedoxTherapies, a privately held company. The acquisition provides Juno with an exclusive license to vipadenant, a small molecule adenosine A2a receptor antagonist that has the potential to disrupt important immunosuppressive pathways in the tumor microenvironment in certain cancers. Juno intends to explore this molecule in combination with its engineered T cell platform and may over time explore it in other areas as well. The upfront consideration for the RedoxTherapies acquisition was $10.0 million in cash. The seller is also eligible to receive payments upon the achievement of clinical, regulatory, and commercial milestones.

Second Quarter 2016 Financial Results
Cash Position: Cash, cash equivalents, and marketable securities as of June 30, 2016 were $1.11 billion compared to $1.13 billion as of March 31, 2016 and $1.22 billion as of December 31, 2015.

Cash Burn: Cash burn in the second quarter of 2016, excluding the $50.0 million opt-in fee from Celgene and cash inflows and outflows from business development, was $55.2 million. Including the cash inflow from Celgene of $50.0 million, and excluding cash inflows and outflows from business development activities, cash burn in the second quarter of 2016 was $5.2 million, compared to $18.5 million in the second quarter of 2015. Included in cash burn in the three months ended June 30, 2016 and 2015 are cash outflows for capital expenditures of $7.4 million and $6.8 million, respectively.

Revenue: Revenue for the three and six months ended June 30, 2016 was $27.6 million and $37.4 million, respectively, compared to $12.5 million for the three and six months ended June 30, 2015. The increase of $15.1 million and $24.9 million in the three and six months ended June 30, 2016, respectively, was due primarily to revenue recognized in connection with the Celgene collaboration and CD19 opt-in as well as milestone revenue from Novartis. Included in revenue for the three and six months ended June 30, 2015 was an upfront fee of $12.3 million received in connection with the Novartis sublicense agreement.

R&D Expenses: Research and development expenses for the three and six months ended June 30, 2016, inclusive of non-cash expenses and computed in accordance with GAAP, were $72.3 million and $146.0 million, respectively, compared to $60.2 million and $118.0 million for the same periods in 2015. The increases in 2016 were primarily due to increased costs incurred to execute Juno’s clinical development strategy, manufacture its product candidates, and expand its overall research and development capabilities, milestones achieved in 2016, and an increase in stock-based compensation expense. These increases were offset by upfront payments made to Fate Therapeutics and Editas in 2015, the gains recognized during the first two quarters of 2016 related to the change in the estimated value of Juno’s contingent consideration liabilities, and the difference between the periods in expense related to Juno’s estimated success payment liability. For the three months ended June 30, 2016 and 2015, Juno recorded expenses of $3.5 million and $4.0 million, respectively, related to Juno’s success payment liability. For the six months ended June 30, 2016, Juno recorded a gain of $3.1 million related to Juno’s success payment liability, compared to an expense of $42.9 million for the same period in 2015, resulting in a decrease of $46.0 million in research and development expense for the six months ended June 30, 2016.

Non-GAAP R&D Expenses: Non-GAAP research and development expenses for the three and six months ended June 30, 2016 were $72.1 million and $152.3 million, respectively, compared to $23.9 million and $40.9 million for the same periods in 2015. Non-GAAP research and development expenses for the three and six months ended June 30, 2016 include $8.9 million and $18.0 million of stock-based compensation expense, respectively, compared to $2.3 million and $4.1 million for the same periods in 2015. Non-GAAP research and development expenses in the first half of 2016 exclude the following:
An expense of $3.5 million for the three months ended June 30, 2016 and a gain of $3.1 million for the six months ended June 30, 2016 associated with the change in the estimated value and elapsed service period for Juno’s potential success payment liabilities to FHCRC and MSK.

Non-cash stock-based compensation expense of $1.2 million and $2.4 million for the three and six months ended June 30, 2016, respectively, related to a 2013 restricted stock award to a co-founding director that became a consultant upon his departure from Juno’s board of directors in 2014.

A gain of $4.5 million and $5.5 million for the three and six months ended June 30, 2016, respectively, associated with the change in the estimated fair value of the contingent consideration liabilities recorded in connection with the Stage and X-Body acquisitions.
Non-GAAP research and development expenses in the first half of 2015 exclude the following:
Expense of $4.0 million and $42.9 million for the three and six months ended June 30, 2015, respectively, associated with the change in estimated value and elapsed accrual period for Juno’s potential success payment liabilities to FHCRC and MSK.

Non-cash stock-based compensation expense of $1.7 million and $3.6 million for the three and six months ended June 30, 2015, respectively, related to a 2013 restricted stock award to a co-founding director that became a consultant upon his departure from Juno’s board of directors in 2014.

An expense of $0.1 million for the three and six months ended June 30, 2015, associated with the change in the estimated fair value of the contingent consideration liabilities recorded in connection with the Stage and X-Body acquisitions.

Upfront payments related to license agreements of $30.8 million for the three and six months ended June 30, 2015 associated with the Editas and Fate Therapeutics collaborations.

G&A Expenses: General and administrative expenses on a GAAP basis for the three and six months ended June 30, 2016 were $16.8 million and $32.8 million, respectively, compared to $20.2 million and $27.6 million for the same periods in 2015. The decrease in the second quarter of 2016 compared to the same period in 2015 was primarily due to lower litigation and business development costs, offset by increased personnel costs, including non-cash stock-based compensation expense, and increased consulting fees including costs related to commercial readiness. The increase in the first half of 2016 compared to the first half of 2015 was primarily due to increased personnel costs, including non-cash stock-based compensation expense, and consulting fees including costs related to commercial readiness, offset by lower litigation and business development expenses. General and administrative expenses include $5.5 million and $10.4 million of non-cash stock-based compensation expense for the three and six months ended June 30, 2016, respectively, compared to $3.0 million and $4.8 million for the same periods in 2015.

GAAP Net Loss: Net loss for the three and six months ended June 30, 2016 was $64.8 million, or $0.64 per share, and $135.9 million, or $1.35 per share, respectively, compared to $66.0 million, or $0.79 per share and $130.9 million, or $1.58 per share for the same periods in 2015.

Non-GAAP Net Loss: Non-GAAP net loss, which incorporates the non-GAAP R&D expense, for the three and six months ended June 30, 2016 was $64.6 million, or $0.64 per share and $142.1 million, or $1.40 per share, respectively, compared to $29.6 million, or $0.35 per share and $53.8 million, or $0.65 per share, respectively, for the same periods in 2015.
A reconciliation of GAAP net loss to non-GAAP net loss is presented below under "Non-GAAP Financial Measures."

2016 Financial Guidance
Juno reaffirms 2016 cash burn guidance, excluding cash inflows or outflows from business development activities, of between $220 million and $250 million.
Operating burn estimated to be between $170 million and $195 million.
Capital expenditures estimated to be between $40 million and $55 million, the vast majority of which are related to one-time infrastructure build-outs.

Alnylam Pharmaceuticals Reports Second Quarter 2016 Financial Results and Highlights Recent Period Progress

On August 4, 2016 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its consolidated financial results for the second quarter 2016, and highlighted recent progress in advancing its pipeline (Press release, Alnylam, AUG 4, 2016, View Source;p=RssLanding&cat=news&id=2193147 [SID:1234514268]).

"We continue to advance our pipeline of now ten investigational RNAi therapeutics, an entirely new and innovative class of medicines, across a broad range of diseases. We believe our two latest stage programs, patisiran and revusiran, have demonstrated encouraging progress for patients with hATTR amyloidosis," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "We also recently presented new results in our hemophilia program showing that a once-monthly, subcutaneous regimen of fitusiran can achieve a median estimated annualized bleeding rate of zero in hemophilia A and B patients. In addition, we presented encouraging initial data in hemophilia patients with inhibitors. Through the end of the year, we are anticipating a very data rich period marked with over six planned clinical readouts – we look forward to sharing our continued progress."

Second Quarter 2016 and Recent Significant Corporate Highlights

Advanced investigational pipeline programs in Genetic Medicine Strategic Therapeutic Area (STAr).
Advanced investigational RNAi therapeutic programs for the treatment of transthyrethin (TTR)-mediated amyloidosis (ATTR amyloidosis).
Reported positive initial 24-month data from ongoing Phase 2 open-label extension (OLE) study with patisiran for the treatment of hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN). Results showed that patisiran can potentially halt or improve neuropathy progression. Patisiran administration was also found to be generally well tolerated in hATTR-PN patients out to 25 months, with no drug-related serious adverse events (SAEs) reported through the data transfer date.
Presented baseline demographic data from APOLLO Phase 3 study of patisiran, revealing enrollment of a globally representative patient population with a wide range of disease severity and TTR mutations.
Reported initial 12-month results from ongoing Phase 2 OLE study with revusiran for the treatment of hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM).
Initiated Phase 1 clinical trial for ALN-TTRsc02, an Enhanced Stabilization Chemistry (ESC)-GalNAc-siRNA conjugate targeting TTR for the treatment of ATTR amyloidosis, which is expected to enable a low volume, once quarterly, subcutaneous dosing regimen.
Reported positive interim clinical results from Phase 1 study of fitusiran for the treatment of hemophilia and rare bleeding disorders (RBD).
Fitusiran achieved a median estimated annualized bleeding rate (ABR) of zero in hemophilia patients without inhibitors. In the initial low-dose cohort of patients with inhibitors, fitusiran achieved antithrombin lowering, increased thrombin generation, and preliminary evidence for reduced bleeding. Fitusiran administration was generally well tolerated in patients with and without inhibitors, with no SAEs related to study drug, and no thromboembolic events or laboratory evidence (based on D-dimer, platelet count, fibrinogen, and/or PT/INR) of pathologic clot formation through the data transfer date.
Continued dosing hemophilia patients in ongoing Phase 1/2 OLE study, with patients currently having received up to 13 months of dosing.
The Company also updated its guidance for Phase 3 initiation, and now plans to start studies in early 2017.
Reported initial clinical results in patients with paroxysmal nocturnal hemoglobinuria (PNH) from ongoing Phase 1/2 study of ALN-CC5 for the treatment of complement-mediated diseases.
Initial data support the potential for ALN-CC5 to reduce the dose and frequency of eculizumab, as well as to improve disease control in eculizumab inadequate responders.
ALN-CC5 was generally well tolerated in patients with PNH after multiple doses, with the majority of adverse events (AEs) being mild or moderate in severity. There were no drug related SAEs or discontinuations due to AEs in the study through the data transfer date.
The Company announces today that the European Medicines Agency (EMA) has granted Orphan Drug Designation to ALN-AS1 for the treatment of acute hepatic porphyrias.
The Company also announces today the publication of pre-clinical data with ALN-GO1 for the treatment of primary hyperoxaluria type 1 (PH1) in the Journal of the American Society of Nephrology (Liebow et al., J Am Soc Nephrol, 2016; doi:10.1681/ASN.2016030338).
Advanced investigational pipeline programs in Cardio-Metabolic Disease STAr.
The Medicines Company announced completion of enrollment in its Phase 2 ORION-1 study for ALN-PCSsc (also known as PCSK9si). The trial enrolled 501 patients with atherosclerotic cardiovascular disease (ASCVD), exceeding the original enrollment target of 480 patients.
Advanced investigational pipeline programs in Hepatic Infectious Disease STAr.
Initiated Phase 1/2 clinical trial with ALN-HBV for the treatment of hepatitis B virus (HBV) infection.
Broke ground on new manufacturing facility in Norton, Massachusetts. The 200,000 square foot, state-of-the-art facility is being built to support the Company’s expanding development pipeline and transition toward commercial stage.
Expanded Management Team with appointments of Adrian Dana, M.D., Vice President of Drug Safety and Pharmacovigilance; Brendan Martin, General Manager, UK and Ireland; Jeffrey Miller, Vice President, General Manager, CC5 Program; and Andrew Slugg, Vice President of Regulatory Affairs.
Upcoming Events in 2H 2016

Alnylam announces today that it plans to present clinical data at these upcoming conferences:
Complete data from Parts A and B (single and multiple ascending dose, respectively) of the ongoing Phase 1 clinical trial of ALN-AS1 in patients who are asymptomatic "high excreters" (ASHE) at the 2016 Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium, being held September 6 – 9, 2016 in Rome, Italy, in an oral presentation on Wednesday, September 7, at 2:15 pm Central European Summer Time (8:15 am ET).
Initial clinical results from the ongoing Phase 1/2 study of ALN-GO1 at the 17th Congress of the International Pediatric Nephrology Association (IPNA), being held September 20 – 24, 2016 in Iguaçu, Brazil, in an oral presentation on Saturday, September 24, at 3:25 pm Brasília Time (2:25 pm ET).
Initial Phase 1/2 data for ALN-AAT at the 12th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS), being held September 25 – 28, 2016 in Montreal, Canada;
Alnylam also announces today that it plans to host an R&D Day on the morning of Friday, December 16, 2016 at the Westin New York at Times Square in New York City.
In addition, in the second half of 2016, Alnylam plans to:
Complete enrollment in ENDEAVOUR Phase 3 study of revusiran;
Present additional clinical data from the fitusiran Phase 1 study and initial data from the Phase 1/2 OLE study;
Start a new Phase 2 trial with ALN-CC5 in inadequate eculizumab responder PNH patients;
Present additional clinical data from the ongoing Phase 1/2 trial of ALN-CC5 in PNH patients;
Present initial ALN-AS1 data in recurrent attack porphyria patients;
Present initial ALN-TTRsc02 Phase 1 data;
File a Clinical Trial Application for a new Genetic Medicine program; and
Consistent with guidance from The Medicines Company, present initial Phase 2 data for ALN-PCSsc.
Upcoming RNAi Roundtables

Alnylam plans to continue hosting its series of online "RNAi Roundtables" in August, September, and October. Upcoming events include:
Fitusiran for the treatment of hemophilia and rare bleeding disorders
Monday, August 22, 10:30 – 11:45 am ET
Akin Akinc, Ph.D., Vice President, General Manager, Fitusiran
Benny Sorensen, M.D., Ph.D., Senior Director, Clinical Research
Guest Speaker: Brian O’Mahony, Chief Executive, Irish Haemophilia Society Ltd. and person living with severe hemophilia B
ALN-CC5 for the treatment of complement-mediated diseases
Wednesday, August 31, 11:00 am – 12:00 pm ET
Jeff Miller, Vice President, General Manager, CC5 Program
Pushkal Garg, M.D., Senior Vice President, Clinical Development
Guest Speaker: Anita Hill, M.D., Ph.D., MRCP, FRCPath, Consultant Haematologist for Leeds Teaching Hospitals NHS Trust, UK, and Lead for the National PNH Service in England
ALN-AS1 for the treatment of acute hepatic porphyrias
Tuesday, September 13, 11:30 am – 12:45 pm ET
John Maraganore, Ph.D., Chief Executive Officer
William Querbes, Ph.D., Associate Director, Research
Guest Speaker: Ariel Lager, living with Acute Intermittent Porphyria
ALN-GO1 for the treatment of primary hyperoxaluria type 1 (PH1)
Tuesday, September 27, 10:00 – 11:00 am ET
Barry Greene, President and Chief Operating Officer
David Erbe, Ph.D., Director, Research
Guest Speaker: Sally-Anne Hulton, M.D., FRCPCH, MRCP, FCP, MBBCh, Consultant Paediatric Nephrologist and Clinical Lead, Birmingham Children’s Hospital NHS Trust
Guest Speaker: Jennifer Lawrence, M.D. (mother of George Tidmore, a PH1 patient)
ALN-HBV for the treatment of hepatitis B virus (HBV) infection
Tuesday, October 11, 9:00 am – 10:00 am ET
Barry Greene, President and Chief Operating Officer
Laura Sepp-Lorenzino, Ph.D., Vice President, Entrepreneur-in-Residence
Guest Speaker: Heiner Wedemeyer, M.D., Managing Senior Physician and Assistant Professor in the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School
Additional details for the RNAi Roundtables will be provided at www.alnylam.com/roundtables.

Financials

"Alnylam continues to maintain a strong balance sheet, ending the second quarter of 2016 with approximately $1.28 billion in cash," said Michael Mason, Vice President, Finance and Treasurer. "Our financial strength allows us to continue to invest in a broad pipeline of investigational RNAi therapeutics across our three STArs, aligned with achievement of our ‘Alnylam 2020′ goals. As for financial guidance this year, we remain on track to end 2016 with greater than $1.0 billion in cash, including $150.0 million in restricted investments."

Cash and Investments

At June 30, 2016, Alnylam had cash, cash equivalents and marketable securities, and restricted investments of $1.28 billion, as compared to $1.28 billion at December 31, 2015.

Credit Agreements

In April 2016, Alnylam entered into $150.0 million of term loan agreements, related to the build out of the Company’s new manufacturing facility, that mature in April 2021. Interest on the borrowings is calculated based on LIBOR plus 0.45 percent. The obligations under the term loan agreements are secured by cash collateral in an amount equal to, at any given time, at least 100 percent of the principal amount of all term loans outstanding under the agreements at such time.

GAAP Net Loss

The net loss according to accounting principles generally accepted in the U.S. (GAAP) for the second quarter of 2016 was $90.1 million, or $1.05 per share on both a basic and diluted basis (including $15.8 million, or $0.18 per share of non-cash stock-based compensation expense), as compared to a net loss of $71.8 million, or $0.85 per share on both a basic and diluted basis (including $10.2 million, or $0.12 per share of non-cash stock-based compensation expense), for the same period in the previous year.

Revenues

Revenues were $8.7 million in the second quarter of 2016 and 2015. Revenues for the second quarter of 2016 included $5.4 million from the company’s alliance with Sanofi Genzyme and $3.3 million from the company’s alliance with The Medicines Company. The company expects net revenues from collaborators to increase during the second half of 2016 due to an expected increase in expense reimbursement from Sanofi Genzyme.

Research and Development Expenses

Research and development (R&D) expenses were $83.2 million in the second quarter of 2016, which included $9.3 million of non-cash stock-based compensation, as compared to $67.0 million in the second quarter of 2015, which included $6.1 million of non-cash stock-based compensation. The increase in R&D expenses for the quarter ended June 30, 2016 as compared to the prior year period was due primarily to higher compensation and related expenses and non-cash stock-based compensation expenses resulting from a significant increase in headcount during the period as the company continues to advance and expand its development pipeline. In addition, clinical trial and manufacturing and external services expenses increased during the quarter ended June 30, 2016 as compared to the quarter ended June 30, 2015 as a result of the significant advancement of the company’s Genetic Medicine pipeline. The company expects that R&D expenses during the second half of 2016 will increase compared to the first half of 2016 as it continues to develop its pipeline and advance its product candidates into clinical trials, but that such expenses will be variable on a quarterly basis depending on the timing of manufacturing batches, clinical trial enrollment, and non-cash stock-based compensation expenses.

General and Administrative Expenses

General and administrative (G&A) expenses were $18.0 million in the second quarter of 2016, which included $6.5 million of non-cash stock-based compensation, as compared to $14.6 million in the second quarter of 2015, which included $4.0 million of non-cash stock-based compensation. The increase in G&A expenses for the quarter ended June 30, 2016 as compared to the prior year period was due primarily to an increase in compensation and related expenses and non-cash stock-based compensation expense due to an increase in headcount. The company expects that G&A expenses during the second half of 2016 will remain relatively consistent with the first half of 2016.