On November 1, 2018 Cytokinetics, Incorporated (Nasdaq: CYTK) reported financial results for the third quarter of 2018. Net loss for the third quarter was $22.8 million, or $0.40 per share, compared to a net loss for the third quarter of 2017 of $32.4 million, or $0.60 per share. Cash, cash equivalents and investments totaled $210.3 million at September 30, 2018 (Press release, Cytokinetics, NOV 1, 2018, View Source [SID1234530581]).

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"With five programs advancing in development, we were pleased to report progress of our expanded pipeline of muscle biology directed potential medicines as recently outlined at our R&D Day," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "We look forward to beginning multiple trials across our cardiac muscle programs before year-end as well as soon completing enrollment in FORTITUDE-ALS, our Phase 2 clinical trial of reldesemtiv in patients with ALS, with results expected next year. I believe that the company has never been better positioned programmatically, operationally and financially to potentially deliver on the promise of our pioneering leadership in muscle biology."

Recent Highlights and Upcoming Milestones

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

Continued patient enrollment in GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil. Enrollment has surpassed 70 percent completion with over 5,800 patients randomized to date having the high-risk profile intended by the trial design. We expect completion of patient enrollment in GALACTIC-HF to occur during the first half of 2019. We also expect that GALACTIC-HF will have accrued a sufficient number of events to enable the Data Monitoring Committee to conduct a first interim analysis for the trial, the design of which is tied to the potential for futility, in the first half of 2019.

Conducted readiness activities in advance of the initiation of METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure). METEORIC-HF is a Phase 3, randomized, placebo-controlled, double-blind, parallel group, multicenter clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) following 20 weeks of treatment. Cytokinetics is working together with Amgen towards the objective of starting METEORIC-HF by the end of 2018.
AMG 594 (cardiac troponin activator)

Continued pre-clinical development of AMG 594 and filed an IND in collaboration with Amgen. AMG 594 is a novel, first-in-class, selective, oral, small molecule cardiac troponin activator, discovered under a joint research program with Amgen. In preclinical models, AMG 594 increases myocardial contractility by binding to cardiac troponin through an allosteric mechanism that sensitizes the cardiac sarcomere to calcium. Based on preclinical data, AMG 594 may offer differentiated efficacy and dose-related convenience relative to omecamtiv mecarbil.

We expect that Amgen will initiate a Phase 1 program for AMG 594 before the end of the year to assess its safety, tolerability, pharmacokinetics and its potential to increase cardiac function in healthy volunteers.
CK-3773274 (CK-274, cardiac myosin inhibitor)

Continued pre-clinical development and filed an IND for CK-274. CK-274 is a novel, oral, small molecule cardiac myosin inhibitor that company scientists discovered independent of its collaborations. CK-274 arose from an extensive next-generation chemical optimization program conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into best-in-class potential in clinical development. In preclinical models, CK-274 reduces myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site preventing myosin from entering a force producing state.

We expect to initiate a Phase 1 program for CK-274 before the end of the year to assess its safety, tolerability, pharmacokinetics and its effect on cardiac function in healthy volunteers.
Skeletal Muscle Program

reldesemtiv (next-generation FSTA)

Announced that additional results from the Phase 2 clinical study of reldesemtiv in patients with spinal muscular atrophy (SMA) were presented by John W. Day, M.D., Ph.D., Professor of Neurology and Pediatrics (Genetics), Stanford University at the 2018 Muscle Study Group Scientific Meeting in Oxford, UK, showing sustained increases in 6MWD and MEP four weeks after discontinuation of study drug.

Continued site activation and patient enrollment in FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS), the Phase 2 clinical trial of reldesemtiv which is designed to assess the change from baseline in percent predicted slow vital capacity and other measures of skeletal muscle function after 12 weeks of treatment with reldesemtiv in patients with ALS. FORTITUDE-ALS has enrolled over 400 patients toward the objective of 445 patients in the trial and is being conducted by Cytokinetics in collaboration with Astellas. We expect to complete enrollment in FORTITUDE-ALS in Q4 2018 with results from this clinical trial expected in the first half of 2019.

With Astellas, announced the Phase 2 clinical trial of reldesemtiv in patients with chronic obstructive pulmonary disease (COPD), which was designed to assess its effect on physical function, did not meet the primary endpoint and did not demonstrate a statistically significant treatment difference in any of the secondary endpoints. Adverse events were similar between groups receiving reldesemtiv and placebo.

With Astellas, announced that an interim analysis of the Phase 1b clinical trial of reldesemtiv in elderly subjects with limited mobility, which was designed to assess its effect on measures of physical function, was recently conducted. The Data Monitoring Committee determined that the pre-defined criteria for lack of efficacy of reldesemtiv had been met; Astellas has proceeded to notify investigators to halt further enrollment in the trial.
Pre-Clinical Development and Ongoing Research

Continued pre-clinical development of CK-3762601 (CK-601), a next-generation fast skeletal muscle troponin activator (FSTA) into IND-enabling studies under our collaboration with Astellas.

Continued research in collaboration with Astellas directed to the discovery of next-generation skeletal muscle activators. The companies are continuing their joint research program with Astellas providing sponsorship of Cytokinetics’ activities through 2019.

Continued independent research activities directed to our other muscle biology research programs.
Corporate

Announced that The ALS Association Golden West Chapter is the inaugural recipient of the Cytokinetics Communications Fellowship, an annual grant from the company intended to support increased capacity and community engagement for nonprofit organizations.
Financials

Revenues for the three and nine months ended September 30, 2018 were $10.6 million and $22.1 million, respectively, compared to $6.2 million and $13.4 million for the corresponding periods in 2017. Revenues for the first nine months of 2018 stemmed from our strategic alliance with Astellas.

Research and development expenses for the third quarter of 2018 decreased to $21.4 million from $24.9 million for the third quarter of 2017, primarily due to cessation of development of tirasemtiv in late 2017, offset in part by increased spending in clinical trials of reldesemtiv and preclinical activities for CK-274 and other potential drug candidates. Research and development expenses for the first nine months of 2018 increased to $65.9 million from $64.0 million for the first nine months of 2017, primarily due to increased spending in clinical trials of reldesemtiv and preclinical activities for CK-274 as well as other potential drug candidates, offset in part by suspension of development of tirasemtiv in late 2017.

General and administrative expenses for the three and nine months ended September 30, 2018 decreased to $7.2 million and $23.7 million, respectively, from $9.7 million and $26.2 million for the same periods in 2017, respectively, primarily due to reduced pre-commercial activities for tirasemtiv and reduced other corporate activities.

Conference Call and Webcast Information

Members of Cytokinetics’ senior management team will review the company’s third quarter results via a webcast and conference call today at 4:30 PM Eastern Time. The webcast can be accessed through the Investors & Media section of the Cytokinetics website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by dialing either (866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078 (international) and typing in the passcode 9785146.

An archived replay of the webcast will be available via Cytokinetics’ website until November 8, 2018. The replay will also be available via telephone by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (international) and typing in the passcode 9785146 from November 1, 2018 at 7:30 PM Eastern Time until November 8, 2018.

On November 1, 2018 Emergent BioSolutions Inc. (NYSE: EBS) reported financial results for the quarter and nine months ended September 30, 2018 (Press release, Emergent BioSolutions, NOV 1, 2018, View Source [SID1234530579]).

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Our financial and operational performance is solidly in line with expectations and we are confident in a strong finish to the year, driven by our organic business as well as the impact of the PaxVax and Adapt Pharma acquisitions," said Daniel J. Abdun-Nabi, CEO of Emergent BioSolutions. He continued, "Strategically, we have broadened our reach into the public health threats market, strengthened our portfolio of unique products, and expanded the patients and customers that we serve. Operationally, we have added substantial manufacturing and sales capabilities, diversified our product development pipeline, and strengthened our pool of engaged and talented employees. Financially, we now expect to achieve our 2020 revenue goal of at least $1 billion in 2019, a full year ahead of schedule, bolstering our ability to create long-term shareholder value."

Richard S. Lindahl, CFO of Emergent BioSolutions, said, "The acquisitions of Adapt Pharma and PaxVax create a step-change forward for Emergent. On a combined basis, we expect the two entities to contribute between $270 and $300 million of incremental revenue and to be accretive to adjusted net income and adjusted EBITDA in 2019. We are actively engaged in integration and our entire team is excited to move forward together as we continue to diversify our revenue sources, realize scale efficiencies and drive strong cash flow from the now larger Emergent business operations."

Q3 2018 AND RECENT BUSINESS ACCOMPLISHMENTS
Acquisitions
·
Acquired specialty vaccines company PaxVax and its U.S. Food and Drug Administration (FDA) approved vaccines for typhoid, Vivotif (Typhoid Vaccine Live Oral Ty21a), and cholera, Vaxchora (Cholera Vaccine, Live, Oral), along with a development pipeline focused on infectious disease vaccines and related U.S.- and Europe-based manufacturing infrastructure.
·
Acquired Adapt Pharma and its flagship product NARCAN (naloxone HCl) Nasal Spray, the first and only needle-free presentation of naloxone approved by the FDA and Health Canada, for the emergency treatment of known or suspected opioid overdose, and the leading community-use option for naloxone delivery.
Product Development
·
Initiated a Phase 1 clinical study of ZIKV-IG, the Company’s anti-Zika virus immune globulin being developed as a therapeutic intervention against Zika virus disease; the candidate was granted Fast Track designation by the FDA in December 2017.
Financing
·
To fund the recent acquisitions of PaxVax and Adapt Pharma and pay related fees, costs, and expenses for both transactions, the Company incurred a total of $768 million of debt; this debt was incurred pursuant to an amended and restated credit facility that provides up to $1.05 billion of financing through a $600 million revolver and a $450 million term loan.

2018 FINANCIAL PERFORMANCE

(I) Quarter Ended September 30, 2018 (Unaudited)

Revenues

Total Revenues
For Q3 2018, total revenues were $173.7 million, an increase of 16% over 2017. Total revenues reflect a significant increase in product sales.

Product Sales
For Q3 2018, product sales were $133.3 million, an increase of $19.0 million or 17% as compared to 2017. The increase primarily reflects sales of ACAM2000, (Smallpox (Vaccinia) Vaccine, Live) and Raxibacumab injection, a fully human monoclonal antibody, both acquired in Q4 2017, (included in Other product sales).

Contract Manufacturing
For Q3 2018, revenue from the Company’s contract manufacturing operations was $22.2 million, an increase of $3.3 million or 17% as compared to 2017. The increase primarily reflects increased manufacturing services for existing commercial customers at the Company’s Camden site.

Contracts and Grants
For Q3 2018, revenue from the Company’s development-based contracts and grants was $18.2 million, an increase of $2.0 million or 12% as compared to 2017. The increase primarily reflects increased R&D activities related to certain ongoing funded development programs.

Operating Expenses

Cost of Product Sales and Contract Manufacturing
For Q3 2018, cost of product sales and contract manufacturing was $73.2 million, an increase of $28.7 million or 64% as compared to 2017. The increase primarily reflects the impact of an increase in Other product sales associated principally with ACAM2000 and Raxibacumab, which were acquired in the fourth quarter of 2017, offset by lower BioThrax (Anthrax Vaccine Adsorbed) sales during the quarter.

Research and Development (Gross and Net)
For Q3 2018, gross R&D expenses were $37.0 million, an increase of $14.3 million or 63% as compared to 2017. The increase primarily reflects an increase in costs associated with contract development services.

For Q3 2018, net R&D expense, which reflects investments made in development programs that are not currently funded in whole or in part by third-party partners and is calculated as gross research and development expenses minus contracts and grants revenue, was $18.8 million, an increase of $12.3 million or 189% as compared to 2017. The increase primarily reflects investment in process improvements related to ACAM2000 at the Canton site and increased costs associated with the Phase 2 clinical trial for the FLU-IGIV program. The Q3 2018 net R&D expense was 12% of net revenue (total revenue less contracts & grants).

Selling, General and Administrative
For Q3 2018, selling, general and administrative expenses were $42.1 million, an increase of $7.6 million or 22% as compared to 2017. The increase primarily reflects higher acquisition related (diligence and legal) costs associated with the PaxVax and Adapt Pharma transactions.

Income Taxes
For Q3 2018, the provision for income tax expense in the amount of $0.6 million includes a discrete benefit of $5.6 million primarily related to finalizing positions taken on the Company’s 2017 U.S. federal and state income tax filings and stock compensation activity, resulting in an effective tax rate of 3%.

Net Income & Adjusted Net Income
For Q3 2018, the Company recorded net income of $20.9 million, or $0.41 per diluted share, versus net income of $33.6 million, or $0.68 per diluted share, in 2017. (1)

For Q3 2018, the Company recorded adjusted net income of $28.2 million, or $0.55 per diluted share, versus adjusted net income of $37.1 million, or $0.73 per diluted share, in 2017. (2)

EBITDA & Adjusted EBITDA
For Q3 2018, the Company recorded EBITDA of $34.4 million, or $0.67 per diluted share, versus $57.5 million, or $1.14 per diluted share, in 2017. (2)

For Q3 2018, the Company recorded adjusted EBITDA of $39.6 million, or $0.77 per diluted share, versus $60.5 million, or $1.20 per diluted share, in 2017. (2)

(II) Nine Months Ended September 30, 2018 (Unaudited)

Revenues

Total Revenues
For the nine months of 2018, total revenues were $511.7 million, an increase of $144.6 million or 39% over 2017. Total revenues reflect a significant increase in product sales and contract development and manufacturing services revenue.

Product Sales
For the nine months of 2018, product sales were $389.1 million, an increase of $129.2 million or 50% as compared to 2017. The increase primarily reflects sales of ACAM2000 and Raxibacumab, both acquired in Q4 2017.

Selling, General and Administrative
For the nine months of 2018, selling, general and administrative expenses were $121.8 million, an increase of $20.3 million or 20% as compared to 2017. The increase primarily reflects higher acquisition related (diligence and legal) costs associated with the PaxVax and Adapt Pharma transactions, as well as non-capitalized costs associated with critical IT systems improvements and higher non-cash compensation expenses associated with the Company’s equity awards program.

Income Taxes
For the nine months of 2018, the provision for income tax expense in the amount of $11.8 million includes a discrete benefit of $8.7 million primarily related to stock compensation activity and finalizing positions taken on the Company’s 2017 US federal and state income tax filings, resulting in an effective tax rate of 15%.

Net Income & Adjusted Net Income
For the nine months of 2018, the Company recorded net income of $66.2 million, or $1.29 per diluted share, versus net income of $48.7 million, or $1.03 per diluted share, in 2017. (1)

For the nine months of 2018, the Company recorded adjusted net income of $81.4 million, or $1.59 per diluted share, versus adjusted net income of $57.8 million, or $1.15 per diluted share, in 2017. (2)

EBITDA & Adjusted EBITDA
For the nine months of 2018, the Company recorded EBITDA of $116.7 million, or $2.28 per diluted share, versus $100.8 million, or $2.01 per diluted share, in 2017. (2)

For the nine months of 2018, the Company recorded adjusted EBITDA of $123.9 million, or $2.42 per diluted share, versus $108.7 million, or $2.17 per diluted share, in 2017. (2)

2018 FINANCIAL FORECAST & OPERATIONAL GOALS
The company is revising its financial forecast for 2018. The revised forecast reflects:
·
the strength of the organic business performance (excluding acquisitions, financing and other related costs), which is expected to be at the higher end of the previous forecast;
·
the incremental impact in the fourth quarter of the operations of PaxVax and Adapt Pharma;
·
a total of approximately $50 million in pre-tax transaction and integration costs, preliminary purchase accounting impacts and additional interest expense related to these recent acquisitions; and
·
an estimated effective tax rate of approximately 22% to 23%.

FOOTNOTES
(1)
See "Calculation of Diluted Earnings Per Share."
(2)
See "Reconciliation of Net Income to Adjusted Net Income, EBITDA and Adjusted EBITDA" for a definition of terms and a reconciliation table.
(3)
The Company reintroduced the use of Adjusted EBITDA following the closing of the acquisitions of PaxVax and Adapt Pharma, which excludes additional specified items that can be highly variable and the non-cash impact of certain purchase accounting adjustments, in order to provide a more complete understanding of factors and trends affecting the Company’s business.

CONFERENCE CALL AND WEBCAST INFORMATION
Company management will host a conference call at 5:00 pm (Eastern Time) today, November 1, 2018, to discuss these financial results. This conference call can be accessed live by telephone or through Emergent’s website:

Live Teleconference Information:
Dial in: [US] (855) 766-6521; [International] (262) 912-6157
Conference ID: 93346559

Live Webcast Information:
Visit View Source for the live webcast feed.

On November 1, 2018 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic diseases, and cancer, reported that initial data from its ongoing Phase 1 dose-escalation study of XmAb14045, a CD123 x CD3 bispecific antibody, in patients with relapsed/refractory acute myeloid leukemia (AML) will be presented in an oral session at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Monday, December 3, 2018 (Press release, Xencor, NOV 1, 2018, View Source [SID1234530578]).

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Key Highlights from the Abstract

At data cut off on June 27, 2018, 63 patients with relapsed/refractory AML and one patient with B cell acute lymphoblastic leukemia had received XmAb14045. Patients had a median age of 61 years and were heavily pretreated, having a median of three prior therapies, and 30% (n=19/64) had undergone prior allogeneic stem cell transplantation.
No MTD was identified, and cytokine release syndrome (CRS) was the most common toxicity occurring in 49 of 64 patients (77%). Seven patients (11%) experienced Grade 3 or 4 CRS. CRS was generally manageable with premedication.
23% of evaluable patients with AML achieved either complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest dose levels studied to date (1.3 and 2.3 mcg/kg weekly; n=3/13).
Two patients with responses were bridged to stem cell transplantation, and the third was ineligible but remained in remission at 14+ weeks after initiating therapy.
"Initial results from the ongoing study of our lead bispecific antibody XmAb14045 in heavily pretreated patients with acute myeloid leukemia demonstrate that several patients achieved complete remissions," said Paul Foster, M.D., senior vice president and chief medical offer at Xencor. "XmAb14045 is a full-length immunoglobulin designed to be dosed intermittently. We continue to optimize dosing regimen as we advance the Phase 1 study."

Presentation Details

Abstract:

763

Title:

Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of XmAb14045, a CD123 x CD3 T Cell-Engaging Bispecific Antibody: Initial Results of a Phase 1 Study

Presenter:

Farhad Ravandi, M.D., Professor of Medicine and Chief of Section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – M.D. Anderson Cancer Center

Session:

616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: New Treatment Strategies

Date & Time:

Monday, December 3, 2018, 2:45 p.m. PST

Location:

Manchester Grand Hyatt San Diego, Seaport Ballroom F

The accepted abstract is now available on the ASH (Free ASH Whitepaper) conference website.

Analyst & Investor Event and Webcast Information
Xencor will host an analyst and investor event on Monday, December 3, 2018 from 8:00 to 10:00 p.m. PST with formal remarks at 8:30 p.m. PST. The event will feature a discussion of the data presented at ASH (Free ASH Whitepaper) and Xencor’s bispecific oncology pipeline. The event will be webcast live and can be accessed under Events & Presentations in the Investors section of www.xencor.com, where it will be archived for 30 days.

About XmAb14045
XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

On November 1, 2018 bluebird bio, Inc. (NASDAQ: BLUE) reported financial results and business highlights for the third quarter ended September 30, 2018 (Press release, bluebird bio, NOV 1, 2018, View Source [SID1234530577]).

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"2018 has been a year of tremendous growth and transition at bluebird, notably exemplified by the filing of our first regulatory application for LentiGlobin in transfusion dependent β-thalassemia (TDT) with the European Medicines Agency (EMA)," said Nick Leschly, chief bluebird. "As we prepare to serve patients with LentiGlobin first in Europe, and later in the U.S., we are advancing the development of our programs in SCD and multiple myeloma, the latter in collaboration with Celgene. We have outlined an accelerated development plan utilizing a surrogate endpoint that we believe allows us to continue to evolve our understanding of the potential of LentiGlobin in patients with SCD. In cerebral adrenoleukodystrophy (CALD), we have regulatory alignment on the path forward and are on track. In multiple myeloma, we and Celgene have begun to lay the plans to bring bb2121 into earlier lines of therapy, while building for the future with bb21217. We look forward to sharing clinical and pre-clinical data across our portfolio – a breadth of progress that is a testament to the tireless work of the bluebird flock."

"The emerging data from our LentiGlobin program in SCD demonstrate the potential to rapidly produce high levels of anti-sickling HbAT87Q that we hope will fundamentally reduce sickling and hemolysis, thereby providing a meaningful increase in total hemoglobin and leading to a reduction in clinical events," said David Davidson, M.D., chief medical officer, bluebird bio. "We continue to have ongoing dialogue with the U.S. Food and Drug Administration (FDA), in the context of our Regenerative Medicine Advanced Therapy (RMAT) designation, and now plan to pursue an accelerated development path that may allow us to initially validate, and then leverage these clinically meaningful biomarkers to form the primary endpoint of a registration-enabling study for patients with a history of vaso-occlusive events (VOEs). We also plan to conduct future clinical investigation of LentiGlobin in patients with other SCD phenotypes, including those at risk of stroke."

Recent Highlights

TDT

LENTIGLOBIN MAA ACCEPTANCE – In October 2018, the EMA accepted for review the company’s marketing authorization application (MAA) for its investigational LentiGlobin gene therapy for the treatment of adolescents and adults with TDT and a non-β0/β0 genotype. LentiGlobin was previously granted an accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the EMA in July 2018, potentially reducing the EMA’s active review time of the MAA from 210 days to 150 days.
SCD

LENTIGLOBIN DEVELOPMENT STRATEGY – Based on ongoing discussions with the FDA, bluebird bio is modifying and expanding its clinical development plans to explore efficacy endpoints that may allow the company to pursue a more accelerated development path in the United States for the treatment of patients with SCD who have a history of VOEs. Enrollment of the HGB-206 study has been expanded to enroll up to 50 adult and adolescent patients. The expanded HGB-206 study has a new primary efficacy endpoint based on HbAT87Q and total hemoglobin, and a key secondary endpoint of frequency of VOEs. As modified, the HGB-206 study will increase the overall set of clinical data regarding the relationship between anti-sickling hemoglobin and clinical outcomes and has the potential to validate the new primary efficacy endpoint as a surrogate endpoint for other SCD clinical outcomes such as VOEs. In 2019, bluebird bio intends to initiate a multi-site, international Phase 3 study of LentiGlobin for the treatment of patients with SCD and a history of VOEs with the same primary and secondary endpoints, and comparable design, as the HGB-206 study. bluebird bio is also engaged in ongoing discussions with the EMA regarding proposed development plans for LentiGlobin in SCD in Europe.
CALD

UPDATED DATA AT THE SOCIETY FOR THE STUDY OF INBORN ERRORS OF METABOLISM SYMPOSIUM – In September 2018, bluebird bio announced updated results from the Phase 2/3 Starbeam study (ALD-102) of its investigational Lenti-D gene therapy in boys 17 years of age and under with CALD, and initial data from ALD-103, the ongoing observational study of outcomes from allogeneic hematopoietic stem cell transplant (allo-HSCT) in boys 17 years of age and under with CALD. bluebird bio has also reached general agreement with the FDA and the EMA to use data from ALD-102 and ALD-103 to support future marketing applications for Lenti-D in CALD.
ALD-104 STUDY – In early 2019, bluebird bio intends to initiate a multi-site Phase 3 study of the Lenti-D product candidate for the treatment of patients with CALD to enable access following completion of enrollment in the Starbeam study, and to evaluate the suitability of additional conditioning regimens for use with the Lenti-D product candidate.
COMPANY

REGENERON COLLABORATION – In August 2018, bluebird bio and Regeneron Pharmaceuticals, Inc. (Regeneron) announced a collaboration to apply their respective technology platforms to the discovery, development and commercialization of novel immune cell therapies for cancer. The collaborators will specifically leverage Regeneron’s VelociSuite technology platforms for the discovery and characterization of fully human antibodies, as well as T cell receptors (TCRs) directed against tumor-specific proteins and peptides, and bluebird bio will contribute its field-leading expertise in gene transfer and cell therapy.
GRITSTONE COLLABORATION – In August 2018, bluebird bio and Gritstone Oncology, Inc. (Gritstone) announced a collaboration to utilize Gritstone’s proprietary technology platform to identify and validate tumor-specific targets and provide TCRs directed to selected targets for use in bluebird’s gene therapy products. bluebird bio will conduct all development, manufacturing and commercial activities.
STRENGTHENED BALANCE SHEET – In July 2018, bluebird bio raised approximately $600.6 million in net proceeds through a public equity offering. bluebird bio anticipates that its cash, cash equivalents and marketable securities will be sufficient to fund operations into 2022 based on the company’s current business plan.
Upcoming Anticipated Milestones

TDT
Presentation of LentiGlobin clinical data from the Northstar (HGB-204) clinical study in patients with TDT at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting
Presentation of LentiGlobin clinical data from the Northstar-2 (HGB-207) clinical study in patients with TDT and non-β0/β0 genotypes at the ASH (Free ASH Whitepaper) Annual Meeting
Presentation of LentiGlobin clinical data from the Northstar-3 (HGB-212) clinical study in patients with TDT and the β0/β0 genotype at the ASH (Free ASH Whitepaper) Annual Meeting
SCD
Presentation of LentiGlobin clinical data from the HGB-206 clinical study in patients with SCD at the ASH (Free ASH Whitepaper) Annual Meeting
Presentation early data from the investigator-initiated Phase 1 study of shRNAmiR lentiviral vector targeting BCL11A for autologous gene therapy in SCD at the ASH (Free ASH Whitepaper) Annual Meeting
Multiple Myeloma
Presentation of bb21217 clinical data from the CRB-402 clinical study in patients with relapsed/refractory multiple myeloma at the ASH (Free ASH Whitepaper) Annual Meeting
Initiation by Celgene of a Phase 3 clinical study of bb2121 in third line multiple myeloma
Third Quarter 2018 Financial Results

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2018 and December 31, 2017 were $2.0 billion and $1.6 billion, respectively. The increase in cash, cash equivalents and marketable securities is primarily related to the completion of a public offering of common stock in July 2018, which raised net proceeds of approximately $600.6 million, and the receipt of $100.0 million from Regeneron made in connection with the company’s collaboration with Regeneron which was entered into in August 2018. The overall increase in cash, cash equivalents and marketable securities was offset by $40.0 million paid to Gritstone in connection with the company’s collaboration with Gritstone, which was also entered into in August 2018, and cash used in operating activities.
Revenues: Total revenues were $11.5 million for the three months ended September 30, 2018 compared to $7.7 million for the three months ended September 30, 2017. Total revenues were $35.3 million for the nine months ended September 30, 2018 compared to $31.3 million for the nine months ended September 30, 2017. The increase in both periods was primarily attributable to increased manufacturing services under the company’s collaboration agreement with Celgene, offset by decreased license and royalty revenue.
R&D Expenses: Research and development expenses were $116.7 million for the three months ended September 30, 2018 compared to $61.5 million for the three months ended September 30, 2017. Research and development expenses were $328.9 million for the nine months ended September 30, 2018 compared to $180.5 million for the nine months ended September 30, 2017. The increase in both periods was driven by costs incurred to advance and expand the company’s pipeline and is attributable to increased clinical trial-related costs and manufacturing costs for development programs, increased laboratory expenses, increased employee-related costs due to headcount growth, and increased license milestones and fees under the company’s strategic collaboration and license agreements.
G&A Expenses: General and administrative expenses were $44.5 million for the three months ended September 30, 2018 compared to $23.0 million for the three months ended September 30, 2017. General and administrative expenses were $120.6 million for the nine months ended September 30, 2018 compared to $64.5 million for the nine months ended September 30, 2017. The increase in both periods was attributable to increases in employee-related costs due to increased headcount to support overall growth, commercial-readiness activities, and professional and consulting fees.
Net Loss: Net loss was $145.5 million for the three months ended September 30, 2018 compared to $78.8 million for the three months ended September 30, 2017. Net loss was $406.6 million for the nine months ended September 30, 2018 compared to $218.4 million for the nine months ended September 30, 2017.
Conference Call & Webcast Information
bluebird bio will host a conference call and live webcast at 8:00 a.m. ET on Friday, November 2, 2018. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the company’s website at www.bluebirdbio.com. Alternatively, investors may listen to the call by dialing (844) 825-4408 from locations in the United States or (315) 625-3227 from outside the United States. Please refer to conference ID number 5595967.

On November 1, 2018 bluebird bio, Inc. (Nasdaq: BLUE) reported that new data from its early- and late-stage investigational gene and cell therapy programs will be presented during the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California, December 1 – 4 (Press release, bluebird bio, NOV 1, 2018, View Source [SID1234530576]).

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"The breadth of data we are presenting at ASH (Free ASH Whitepaper) illustrates the potential of our gene and cell therapies to provide meaningful benefits to people living with severe diseases," said David Davidson, M.D., chief medical officer, bluebird bio. "Our presentations will include data from the pivotal trials of LentiGlobin gene therapy in patients with transfusion-dependent β-thalassemia, bluebird bio’s first treatment under review for potential approval by the European Medicines Agency. We will also share updated data from our study of LentiGlobin in patients with sickle cell disease and initial results from our next generation anti-BCMA CAR T therapy, bb21217, in patients with relapsed/refractory multiple myeloma."

bluebird bio will present initial data from patients with transfusion-dependent β-thalassemia (TDT) with a β0/β0 genotype treated with LentiGlobingene therapy in the Phase 3 Northstar-3 (HGB-212) study as well as updated results, including up to 3.5 years of follow-up, from the completed Phase 1/2 Northstar study (HGB-204).

Abstracts outlining bluebird bio’s accepted data at ASH (Free ASH Whitepaper) will be available on the ASH (Free ASH Whitepaper) conference website at 9:00 a.m. EDT today.

First Data from Clinical Programs

Initial Results from a Phase 1 Clinical Study of bb21217, a Next-Generation Anti-BCMA CAR T Therapy
Presenter: Nina Shah, M.D., University of California San Francisco, San Francisco, Calif.
Date & Time:Sunday, December 2, 2018, 4:45 p.m. PST (7:45 p.m. EST)

bluebird bio’s lead oncology programs, bb2121 and bb21217, are anti-BCMA CAR T programs partnered with Celgene. bb21217 is a next-generation anti-BCMA CAR T cell therapy using the bb2121 CAR molecule with a manufacturing process designed to improve T cell persistence. bb21217 has exhibited improved persistence and increased anti-tumor activity in preclinical animal studies.

This presentation will include early data from the Phase 1 CRB-402 study of bb21217 in patients with relapsed/refractory multiple myeloma. CRB-402 is a two-part (dose escalation and dose expansion), open label, multi-site Phase 1 study of bb21217 in adults with relapsed/refractory multiple myeloma with a projected final enrollment of 50 patients.

Data in the abstract include results as of the data cutoff date of June 15, 2018 for eight patients who have received bb21217. These patients had a median of nine prior lines of therapy (4 – 17 lines) and all received a dose of 150 x 106 CAR+ T cells. The median follow-up after bb21217 infusion was 16 weeks (2 – 27 weeks).

The adverse events observed as of the data cut-off were consistent with known toxicities of CAR T therapies. Five of eight patients developed cytokine release syndrome (CRS); one Grade 1, three Grade 2 and one Grade 3 case. All responded to supportive care with or without tocilizumab. This included one patient with high tumor burden who experienced dose-limiting toxicity (DLT) consisting of Grade 3 CRS and Grade 4 encephalopathy with signs of posterior reversible encephalopathy syndrome on MRI. This patient received tocilizumab, corticosteroids and cyclophosphamide, improved neurologically and achieved a stringent complete response (sCR). Following this event, the dose escalation cohort was divided into two groups based on tumor burden and dosing continued at 150 x 106 CAR+ T cells.

Seven patients were evaluable for initial (one-month) clinical response. Six of seven patients demonstrated clinical response per the International Myeloma Working Group (IMWG) Uniform Response Criteria for multiple myeloma, including one sCR, three very good partial responses (VGPR) and two partial responses (PR). Robust CAR+ T cell expansion during the first 30 days was observed in seven of seven evaluable patients and the two patients evaluable at six months both had CAR vector copies detectable in peripheral blood.

This study is ongoing to evaluate the potential safety and efficacy of treatment with bb21217 and updated results will be shared at the ASH (Free ASH Whitepaper) conference.

Flipping the Switch: Initial Results of Genetic Targeting of the Fetal to Adult Globin Switch in Sickle Cell Patients
Presenter:Erica Esrick, M.D., Pediatric Hematology and Oncology, at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, Mass.
Date & Time:Monday, December 3, 2018, 6:45 p.m. PST (9:45 p.m. EST)

This presentation will include early data from the investigator-initiated Phase 1 study of shRNAmiR lentiviral vector (LVV) targeting BCL11A for autologous gene therapy in SCD. As of July 28, 2018, one patient had received treatment with BCL11a shRNAmiR. In the patient’s immature red blood cells, expression of the BCL11A protein was reduced by approximately 90 percent compared to levels prior to gene therapy. At 76 days following treatment this patient had a sustained overall hemoglobin of >10 g/dL and, compared to what was observed pre-gene therapy, there was a notable absence of irreversibly sickled cells as assessed by peripheral blood smear, a blood test used to identify abnormalities in the number or shape of blood cells.

Adverse events were consistent with myeloablative conditioning, and there have been no product-related adverse events and no SCD-related complications. Updated results will be shared at the ASH (Free ASH Whitepaper) conference.

Oral Presentations

LentiGlobin for Transfusion-Dependent β-Thalassemia

Clinical Outcomes of LentiGlobin Gene Therapy for Transfusion-Dependent β-Thalassemia Following Completion of the Northstar HGB-204 Study (Abstract #167)
Presenter:John Rasko, Ph.D., Central Clinical School Centenary Institute of Cancer Medicine & Cell Biology, University of Sydney, Sydney, Australia
Date & Time: Saturday, December 1, 2018, 3:00 – 3:15 p.m. PST (6:00 – 6:15 p.m. EST), Room 30D
LentiGlobin Gene Therapy for Patients with Transfusion-Dependent β-thalassemia (TDT): Results from the Phase 3 Northstar-2 and Northstar-3 Studies (Abstract #1025)
Presenter:Franco Locatelli, M.D., Ph.D., Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
Date & Time:Monday, December 3, 2018, 7:15 – 7:30 p.m. PST (10:15 – 10:30 p.m. EST), Room 6B
LentiGlobin for Sickle Cell Disease

Current Results of LentiGlobin Gene Therapy in Patients with Severe Sickle Cell Disease Treated Under Refined Protocol (Abstract #1026)
Presenter:John Tisdale, M.D., National Heart, Lung and Blood Institute, Bethesda, Md.
Date & Time:Monday, December 3, 2018, 7:30 – 7:45 p.m. PST (10:30 – 10:45 p.m. EST), Room 6B
bb21217 for Relapsed/Refractory Multiple Myeloma

Initial Results from a Phase 1 Clinical Study of bb21217, a Next-Generation Anti-BCMA CAR T Therapy (Abstract #488)
Presenter: Nina Shah, M.D., University of California San Francisco, San Francisco, Calif.
Date & Time: Sunday, December 2, 2018, 4:45 – 5:00 p.m. PST (7:45 – 8:00 p.m. EST), Room 6B
BCL11a shRNAmiR for Sickle Cell Disease

Flipping the Switch: Initial Results of Genetic Targeting of the Fetal to Adult Globin Switch in Sickle Cell Patients (Abstract #801)
Presenter:Erica Esrick, M.D., Pediatric Hematology and Oncology, Boston Children’s Hospital, Boston, Mass.
Date & Time:Monday, December 3, 2018, 6:45 – 7:00 p.m. PST (9:45 – 10:00 p.m. EST), Room 6B
Preclinical Presentations

Knockout of CBLB Greatly Enhances Anti-Tumor Activity of CAR T Cells (Abstract #338)
Presenter:Kathryn Hooper, bluebird bio, Cambridge, Mass.
Date & Time: Sunday, December 2, 2018, 9:45 – 10:00 a.m. PST (12:45 – 1:00 p.m. EST), Room 28D
Persistence of CRISPR/Cas9-edited Hematopoietic Repopulating Cells with Therapeutically Relevant Reactivation of Fetal Hemoglobin in Nonhuman Primates (Abstract #806)
Presenter:Olivier Humbert, Fred Hutchinson Cancer Center, Seattle Children’s Hospital, Seattle, Wash.
Date & Time:Monday, December 3, 2018, 3:00 – 3:15 p.m. PST (6:00 – 6:15 p.m. EST), Grand Hall C
Poster Presentations

LentiGlobin for Sickle Cell Disease

Outcomes for Initial Patient Cohorts with Up To 33 Months of Follow-up in the HGB-206 Phase 1 Trial (Abstract #1080)
Presenter:Julie Kanter, M.D., Medical University of South Carolina, Charleston, S.C.
Date & Time:Saturday, December 1, 2018, 6:15 – 8:15 p.m. PST (9:15 – 11:15 p.m. EST), Hall GH
Analysis of RBC Properties in Patients with SCD Treated with LentiGlobin Gene Therapy (Abstract #2195)
Presenter:Nicolas Hebert, St. Anthony Research Center, Paris, France
Date & Time: Saturday, December 1, 2018, 6:15 – 8:15 p.m. PST (9:15 – 11:15 p.m. EST), Hall GH
Characterizing the U.S. Population with Severe Manifestations of Sickle Cell Disease Using Real-World Evidence (Abstract #4811)
Presenter:Clark Paramore, bluebird bio, Cambridge, Mass.
Date & Time:Monday, December 3, 2018, 6:00 – 8:00 p.m. PST (9:00 – 11:00 p.m. EST), Hall GH
Investor Event & Webcast Information
bluebird bio will host a live webcast of an investor and analyst event at 8:30 p.m. PST (11:30 p.m. EST) on Monday, December 3, 2018, during the ASH (Free ASH Whitepaper) Annual Meeting. To access the webcast, please visit the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source A replay of the webcast will be available on the bluebird bio website for 90 days following the call.

About LentiGlobin
LentiGlobin is an investigational one-time gene therapy being studied as a potential treatment to address the underlying genetic cause of transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD).

bluebird bio’s clinical development program for LentiGlobin includes ongoing studies around the world with sites in Australia, Germany, Greece, France, Italy, Thailand, the United Kingdom and the United States. In addition, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-303) for people who have participated in bluebird bio-sponsored clinical studies of LentiGlobin for TDT and SCD.

The European Medicines Association (EMA) granted Priority Medicines (PRIME) eligibility and Orphan Medicinal Product designation to LentiGlobin for the treatment of TDT and SCD. LentiGlobin is also part of the EMA’s Adaptive Pathways pilot program, which is part of the EMA’s effort to improve timely access for patients to new medicines.

The U.S. Food and Drug Administration granted LentiGlobin Orphan Drug status and Breakthrough Therapy designation for the treatment of TDT and SCD.