On November 5, 2015 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported business highlights and financial results for the third quarter ended September 30, 2015 (Press release, Agios Pharmaceuticals, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107178 [SID:1234507987]).

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"We have made significant progress this year toward realizing our goal of what’s possible for patients with our IDH inhibitors, by deploying a comprehensive development strategy of speed and breadth with AG-221 and AG-120 in AML and other cancers," said David Schenkein, M.D., chief executive officer at Agios. "In addition, we are pleased to have selected our fifth molecule, AG-519, for clinical development in PK deficiency. This coupled with DRIVE PK, our ongoing Phase 2 study of AG-348, may optimize our potential to help people with this rare genetic disorder."

KEY UPCOMING MILESTONES IN CANCER METABOLISM

Agios anticipates the following milestones from its IDH clinical development programs in collaboration with Celgene:

AG-221: a first-in-class, oral, selective, potent inhibitor of the mutated IDH2 protein

Present new data from the ongoing Phase 1 dose-escalation and expansion studies of AG-221 in advanced IDH2-mutant positive hematologic malignancies at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place December 5-8, 2015 in Orlando.

AG-120: a first-in-class, oral, selective, potent inhibitor of the mutated IDH1 protein

Present first data from the ongoing Phase 1 dose-escalation trial of AG-120 in advanced IDH1-mutant positive solid tumors in an oral presentation at AACR (Free AACR Whitepaper)-EORTC-NCI AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on November 8, 2015 in Boston.

Present new data from the ongoing Phase 1 dose-escalation and expansion studies of AG-120 in advanced IDH1-mutant positive hematologic malignancies at the ASH (Free ASH Whitepaper) Annual Meeting.

Initiate a global registration-enabling Phase 3 study in patients with acute myeloid leukemia (AML) harboring an IDH1 mutation in the first half of 2016.

AG-221 and AG-120 front-line AML combination trials

Initiate a Phase 1b combination study of either AG-221 or AG-120 with standard induction (7+3, Ara-C and idarubicin/daunorubicin) and consolidation (Ara-C, or mitoxantrone with etoposide) chemotherapy in newly diagnosed AML patients eligible for intensive chemotherapy by the end of 2015.

Initiate a Phase 1/2 combination study of either AG-221 or AG-120 with VIDAZA (azacitidine) in newly diagnosed AML patients not eligible for intensive chemotherapy in the first quarter of 2016.

KEY UPCOMING MILESTONES IN RARE GENETIC METABOLIC DISORDERS

AG-348: a novel, first-in-class, oral activator of pyruvate kinase-R (PKR) for the treatment of pyruvate kinase (PK) deficiency

Present data from the Phase 1 healthy volunteers study of AG-348 and new findings from the Natural History Study of PK deficiency (being conducted with Boston Children’s Hospital) at the ASH (Free ASH Whitepaper) Annual Meeting.
AG-519: a novel, oral activator of PKR for the treatment of PK deficiency

Initiate an integrated single ascending dose (SAD) and multiple ascending dose (MAD) placebo-controlled Phase 1 study in healthy volunteers in the first quarter of 2016.
RECENT DEVELOPMENT UPDATES IN CANCER METABOLISM

Agios has provided the following updates on its clinical development programs in collaboration with Celgene:

AG-221

IDHENTIFY, the Phase 3 study of AG-221, was initiated in October. This is an international, multi-center, open-label, randomized clinical trial designed to compare the efficacy and safety of AG-221 versus conventional care regimens in patients 60 years or older with IDH2 mutant-positive AML that is refractory to or relapsed after second- or third-line therapy. This study is being conducted by Celgene.

The expansion phase of the Phase 1 trial of AG-221 is on track and continues to enroll. It includes four cohorts with 25 patients each and a fifth expansion cohort of 125 patients with IDH2 mutant-positive AML who are in second or later relapse, refractory to second-line induction or reinduction treatment, or have relapsed after allogeneic transplantation.
The ongoing Phase 1 trial of AG-221 in IDH2-mutated advanced solid tumors and angioimmunoblastic T-cell lymphoma continues to enroll patients.

AG-120

The expansion phase of the Phase 1 trial of AG-120 is on track and continues to enroll. It includes three expansion cohorts of a total of 175 patients with IDH1-mutated advanced hematologic malignancies, including one cohort with 125 patients with relapsed and/or refractory AML.

The ongoing Phase 1 trial of AG-120 in IDH1-mutated advanced solid tumors continues to enroll.
AG-881: a brain-penetrant, first-in-class, oral, potent pan-inhibitor of the mutated IDH1 and IDH2 proteins

Two Phase 1, open-label, dose-escalation and expansion studies are on track and continue to enroll – the first in advanced IDH mutant-positive solid tumors and the second in patients with advanced IDH mutant-positive hematologic malignancies whose cancer has progressed on a prior IDHm inhibitor therapy.

RECENT DEVELOPMENT UPDATES IN RARE GENETIC DISORDERS OF METABOLISM

AG-348

DRIVE PK, a global Phase 2, open-label safety and efficacy trial in adult, transfusion-independent patients with PK deficiency, is on track and enrolling.
A natural history study of PK deficiency is also ongoing and patient enrollment is on track.

AG-519

Agios selected a fifth molecule for clinical development, AG-519, a novel, oral activator of PKR for the treatment of PK deficiency.

THIRD QUARTER 2015 FINANCIAL RESULTS

Cash, cash equivalents and marketable securities as of September 30, 2015 were $408.0 million, compared to $467.4 million as of December 31, 2014. The decrease was driven by cash used to fund operating activities of approximately $101.2 million, which was offset by funding of approximately $54.8 million made by Celgene during the nine months ended September 30, 2015 related to our collaboration agreements.

Collaboration revenue was $5.5 million for the third quarter of 2015, compared to $33.9 million for the comparable period in 2014. In July 2014, the company amended its collaboration agreement with Celgene. As a result, for the third quarter of 2014 the company recognized a total of $25.9 million under the previous accounting guidance and upon the modification in addition to $8.0 million in revenue subsequent to the modification through September 30, 2014.

Research and development (R&D) expense was $36.0 million, including $4.9 million of stock- based compensation expense in the third quarter of 2015, compared to $25.5 million, including $1.4 million in stock-based compensation expense for the comparable period in 2014. The increase in R&D expense was primarily due to increased costs to support advancement of the company’s lead investigational medicines toward later-stage development.

General and administrative (G&A) expense was $9.9 million, including $4.5 million of stock-based compensation expense, in the third quarter of 2015, compared to $5.2 million, including $1.4 million of stock-based compensation expense, for the comparable period in 2014. The increase in G&A expense was largely due to increased headcount and other professional expenses to support growing operations.

Net loss for the third quarter of 2015 was $40.3 million, compared to net income of $3.7 million for the comparable period in 2014. The third quarter of 2014 includes additional revenue recognition related to the amendment of the company’s collaboration agreement with Celgene.

FINANCIAL GUIDANCE FOR THE FULL YEAR 2015

Agios is reiterating that it expects to end 2015 with more than $350.0 million of cash, cash equivalents and marketable securities. The anticipated year end 2015 cash position does not include any additional program-specific milestone payments. Agios expects that its cash, cash equivalents and marketable securities would be sufficient to fund its operating expenses and capital expenditure requirements until late 2017.

On November 5, 2015 Celgene Corporation (NASDAQ:CELG) reported net product sales of $2,313 million for the third quarter of 2015, an 18 percent increase from the same period in 2014 (Press release, Celgene, NOV 5, 2015, View Source [SID:1234508003]). The negative net impact of currency on net product sales was 2 percent. Third quarter total revenue increased 18 percent to $2,334 million compared to $1,982 million in the third quarter of 2014. Adjusted net income for the third quarter of 2015 increased 26 percent to $1,011 million compared to $806 million in the third quarter of 2014. Adjusted diluted earnings per share (EPS) in the third quarter of 2015 was $1.23 and includes a $0.04 dilutive impact related to the acquisition of Receptos, Inc. For the same period in 2014, adjusted diluted EPS was $0.97. The results of operations for Receptos, Inc. are included in the consolidated financial results from the August 27, 2015 acquisition date.

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Based on U.S. GAAP (Generally Accepted Accounting Principles), Celgene reported a third quarter of 2015 net loss of $34 million or a loss of $0.04 per diluted share. The reported GAAP net loss for the quarter primarily reflects an increase in costs related to strategic transactions including upfront collaboration expenses driven by the Juno Therapeutics collaboration, inclusive of the premium paid to acquire an equity stake, as well as expenses incurred in connection with the acquisition of Receptos. For the third quarter of 2014, net income was $508 million or $0.61 per diluted share.

"Our strong third quarter performance and acceleration of key drivers create significant momentum in our business, further advancing us toward our 2020 targets," said Bob Hugin, Chairman and Chief Executive Officer of Celgene Corporation. "The continued progress of our clinical pipeline and important strategic collaborations have us well-positioned for long-term growth."

Third Quarter 2015 Financial Highlights

Unless otherwise stated, all comparisons are for the third quarter of 2015 compared to the third quarter of 2014. The adjusted operating expense categories presented below exclude share-based employee compensation expense and upfront collaboration payments. Please see the attached Reconciliation of GAAP to Adjusted Net Income for further information.

Net Product Sales Performance

REVLIMID sales for the third quarter increased 12 percent to $1,453 million. U.S. sales of $895 million and International sales of $558 million increased 18 percent and 3 percent year-over-year, respectively. Volume was the main driver of the increase as both market share and duration trends are positive across major geographies.

POMALYST/IMNOVID sales for the third quarter were $257 million, an increase of 42 percent. U.S. sales were $150 million and International sales were $107 million, an increase of 27 percent and 69 percent, respectively. POMALYST/IMNOVID sales were driven by increased volume as both market share and duration trends are positive across major geographies.

ABRAXANE sales for the third quarter were $230 million, an 8 percent increase. U.S. sales of $145 million decreased 4 percent year-over-year and were impacted by competitive dynamics in lung cancer and breast cancer. International sales of $85 million increased 40 percent year-over-year and were positively impacted by increased volume from the ongoing launch for pancreatic cancer in Europe.

OTEZLA sales for the third quarter were $139 million, increasing 55 percent over the second quarter of 2015. U.S. sales were $129 million and International sales were $10 million. OTEZLA uptake and market share gains continued to accelerate in the third quarter in the U.S. with increased contribution from early launch countries in Europe.
All other product sales, which include THALOMID, ISTODAX, VIDAZA and an authorized generic of VIDAZA drug product in the U.S., were $234 million in the third quarter of 2015 compared to $246 million for the third quarter of 2014.

Research and Development (R&D)

Adjusted R&D expenses were $488 million for the third quarter of 2015 compared to $419 million for the third quarter of 2014. The increase was primarily due to an increase in clinical trial activity across the portfolio. On a GAAP basis, R&D expenses were $1,305 million for the third quarter of 2015 and $675 million for the same period in 2014 primarily reflecting an increase in upfront collaboration expenses driven by the Juno Therapeutics collaboration, inclusive of the premium paid to acquire an equity stake.

Selling, General, and Administrative (SG&A)

Adjusted SG&A expenses were $474 million for the third quarter of 2015 compared to $441 million for the third quarter of 2014. The increase was primarily due to investments in support of the global launches of OTEZLA in psoriasis and psoriatic arthritis and REVLIMID in newly diagnosed multiple myeloma. On a GAAP basis, SG&A expenses were $550 million for the third quarter of 2015 compared to $498 million for the same period in 2014.

Cash, Cash Equivalents, and Marketable Securities

In the third quarter of 2015, Celgene purchased approximately 7.1 million of its shares at a total cost of approximately $815 million. As of September 30, 2015, the Company had approximately $4.3 billion remaining under the stock repurchase program.

During the third quarter of 2015, Celgene issued an aggregate of $8 billion in senior unsecured notes in tranches of three-, five-, seven-, ten- and thirty-years. The Company used the net proceeds from the offering primarily to finance the acquisition of Receptos, Inc. as well as for general corporate purposes.

Operating cash flow was $285 million in the third quarter of 2015. Celgene ended the quarter with approximately $7.5 billion in cash, cash equivalents and marketable securities.

2015 Guidance for REVLIMID and ABRAXANE Updated

Total net product sales are expected to be in the range of $9.0 billion to $9.5 billion
REVLIMID net sales are expected to be approximately $5.8 billion, an increase from the previous range of $5.6 billion to $5.7 billion

ABRAXANE net sales are expected to be in the range of $950 million to $1.0 billion, a decrease from the previous range of $1.0 billion to $1.25 billion
Adjusted 2015 operating margin remains unchanged at approximately 52 percent; GAAP operating margin is expected to be approximately 25.2 percent, lowered from approximately 36.4 percent
Adjusted diluted EPS is expected to be in the range of $4.75 to $4.85
GAAP diluted EPS is expected to be in the range of $2.02 to $2.24, a decrease from the previous range of $2.17 to $2.46
Product and Pipeline Updates

Hematology

In October, VIDAZA was approved by the European Commission for the treatment of adult patients aged 65 years or older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplantation. A positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) was granted in September. VIDAZA will receive extended market protection in all its indications for an additional year throughout the European Economic Area.

A Supplementary New Drug Application was filed with the U.S. Food and Drug Administration for the expanded indication of REVLIMID for the treatment of non-del 5q lower risk myelodysplastic syndromes (MDS). The Prescription Drug User Fee Act date for the submission is April 16, 2016.

American Society of Hematology Meeting

At the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December, data presentations expected include:

Data from the phase III cooperative group SWOG S0777 trial comparing REVLIMID, bortezomib, and dexamethasone versus REVLIMID and dexamethasone in patients with newly diagnosed multiple myeloma not intended for immediate autologous stem cell transplant
Data on REVLIMID in novel combinations including elotuzumab, ixazomib and PD-1/PD-L1 compounds in multiple myeloma
Data from phase II trials of luspatercept in beta-thalassemia and MDS
Data from a phase I/II trial AG-221 in patients with IDH2-mutated AML
Data from a phase I trial of AG-120 in advanced hematologic malignancies
Data from phase I/II trials of ACY-1215 in relapsed and/or refractory multiple myeloma

Oncology

At the 2015 San Antonio Breast Cancer Symposium annual meeting in December, data presentations expected include:

Updated data from the GEPARSepto phase III trial with ABRAXANE in neoadjuvant breast cancer
Data from the WSG-ADAPT TN phase II trial comparing ABRAXANE in combination with carboplatin to gemcitabine in triple-negative breast cancer
Updated data from a phase I trial with atezolizumab in combination with ABRAXANE in triple-negative breast cancer

Inflammation & Immunology (I&I)

On August 27, 2015, Celgene completed the acquisition of Receptos, Inc. for approximately $7.1 billion, net of cash and marketable securities acquired. The acquisition of Receptos, Inc. enhances the Company’s I&I portfolio, further diversifies the expected revenue beginning in 2019, and builds upon the Company’s growing expertise in inflammatory bowel disease. The transaction adds ozanimod, a novel, potentially best-in-class, oral, selective sphingosine 1-phosphate 1 and 5 receptor modulator to the Company’s deep and diverse pipeline of potential disease-altering medicines and investigational compounds. Phase III trials with ozanimod in moderate-to-severe ulcerative colitis and relapsing multiple sclerosis are ongoing with data from these trials expected beginning in 2017.

Maintenance data from the phase II TOUCHSTONE trial with ozanimod in moderate-to-severe ulcerative colitis were presented in October at both the American College of Gastroenterology and the United European Gastroenterology: Week annual meetings. In the trial, a significantly greater proportion of patients that continued on to the ozanimod maintenance phase achieved or maintained clinical remission at 32 weeks compared with those on placebo. In addition at 32 weeks, both the high- and low-dose ozanimod arms were statistically significant compared to placebo for clinical response and mucosal healing. In phase II trials, ozanimod had a well-tolerated safety profile.

The phase III SUNBEAM trial with ozanimod in relapsing multiple sclerosis (RMS) completed enrollment ahead of schedule in October. In addition to the ongoing phase III trials with ozanimod in RMS and moderate-to-severe ulcerative colitis, a phase II proof-of-concept trial in moderate-to-severe Crohn’s disease initiated this quarter.

The phase III registration program with GED-0301 in patients with active Crohn’s disease is initiating. The registration-enabling endoscopy trial with GED-0301 in patients with active Crohn’s disease is ongoing and expected to complete enrollment by year-end. A phase II trial with GED-0301 in moderate-to-severe ulcerative colitis is expected to begin by year-end.

One-year data from the phase III LIBERATE (PSOR-010) trial evaluating OTEZLA or injectable etanercept versus placebo in patients with moderate-to-severe plaque psoriasis were presented at the European Academy of Dermatology and Venereology meeting in October. Improvements in PASI scores and disease-related quality of life observed at week 16 were maintained at week 52 in patients randomized to OTEZLA at baseline and in patients who switched from etanercept to OTEZLA at week 16.

Research and Early Development

The previously announced acquisition of Quanticel Pharmaceuticals, Inc. closed in October 2015. Celgene now has access to Quanticel’s proprietary platform for the single-cell genomic analysis of human cancer, as well as Quanticel’s programs that target specific epigenetic modifiers, which are expected to advance Celgene’s pipeline of innovative cancer therapies. Multiple drug candidates from Quanticel are expected to enter into clinical development beginning in early 2016. Celgene acquired Quanticel for $100 million in cash and up to an additional $385 million in contingent payments.

Management Update

Perry Karsen, Chief Executive Officer of Celgene Cellular Therapeutics (CCT), is retiring at the end of 2015. Mr. Karsen’s time with Celgene spanned over 10 years. He served as CEO of CCT since May 2013 and was also Chief Operations Officer from July 2010 until July 2014 and from 2004 to 2009 was Senior Vice President and Head of Worldwide Business Development. Mr. Karsen was instrumental in the acquisition of Pharmion in 2008 which brought VIDAZA to our portfolio of products.

Third Quarter 2015 Conference Call and Webcast Information

Celgene will host a conference call to discuss the third quarter of 2015 operational and financial performance on Thursday, November 5, 2015, at 9 a.m. ET. The conference call will be available by webcast at www.celgene.com. An audio replay of the call will be available from noon November 5, 2015, until midnight ET November 12, 2015. To access the replay in the U.S., dial 1-855-859-2056; outside the U.S. dial 404-537-3406. The participant passcode is 52827642.

On November 5, 2015 Medigene AG (MDG1, Frankfurt, Prime Standard) reported that early clinical data of its dendritic cell (DC) vaccines will be presented at the upcoming ASH (Free ASH Whitepaper) Annual Meeting taking place from December 5 – 8, 2015 in Orlando, Florida, USA, by its partner Oslo University Hospital, Norway (Press release, MediGene, NOV 5, 2015, View Source [SID:1234508023]). The clinical data were collected in an ongoing compassionate use[1] programme conducted by the Oslo University Hospital under the responsibility of Prof. Gunnar Kvalheim. The poster presentation shows data from patients with acute myeloid leukaemia (AML) and is entitled "AML Patients in Minimal Residual Disease Vaccinated with a Novel Generation of Fast Dendritic Cells Expressing WT-1 and PRAME Mount Specific Immune Responses That Relate to Clinical Outcome". The poster will be presented on December 7, 2015 at 6 PM – 8 PM (local time).

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The Oslo University Hospital has an agreement with Medigene for the use of Medigene`s new generation DC vaccines for their ongoing academic clinical studies. Medigene’s DC vaccines are produced according to GMP guidelines at the Department of Cellular Therapy at the Oslo University Hospital. Acute myeloid leukaemia is Medigene’s lead indication in its DC vaccine programme.

Link to the Abstract: View Source

About Medigene’s DC vaccines: The platform for the development of antigen-tailored DC vaccines is the most advanced platform of the three highly innovative and complementary immunotherapy platforms of Medigene Immunotherapies. Currently, Medigene evaluates its DC vaccines in a company-sponsored phase I/II clinical trial in acute myeloid leukaemia (AML). Further studies utilizing Medigene’s DC vaccine technology include two ongoing clinical investigator-initiated trials: a clinical phase I/II trial in AML at the Ludwig-Maximilian University Hospital Großhadern, Munich, and a clinical phase II trial in prostate cancer at Oslo University Hospital. Moreover, a compassionate use programme is being conducted at the Department of Cellular Therapy at Oslo University Hospital.

Dendritic cells (DCs) are the most potent antigen presenting cells of our immune system. Their task is to take up, process and present antigens on their cell surface, which enables them to activate antigen-specific T cells for maturation and proliferation. This way T cells can recognise and eliminate antigen-bearing tumour cells. Dendritic cells can also induce natural killer cells (NK cells) to attack tumour cells. The team of Medigene Immunotherapies GmbH’s scientists has developed new, fast and efficient methods for generating dendritic cells ex-vivo, which have relevant characteristics to activate both T cells and NK cells. The DC vaccines are developed from autologous (patient-specific) precursor cells, isolated from the patient’s blood, and can be loaded with tumor-specific antigens to treat different types of cancer. Medigene’s DC vaccines are in development for the treatment of minimal residual disease or use in combination therapies.

On November 5, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that three posters featuring the company’s research activities are being presented during the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place November 4-8, 2015, in National Harbor, Maryland (Press release, Five Prime Therapeutics, NOV 5, 2015, View Source [SID:1234508048]). The posters will be made available at View Source following the presentations.

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cmFPA008, an Anti-Mouse CSF-1R Antibody, Combines with Multiple Immunotherapies to Reduce Tumor Growth in Nonclinical Models
Bellovin D, Wondyfraw N, Levin A, et al
Thursday, November 5, 2015

The authors sought to determine whether inhibition of CSF1R when combined with other immuno-oncology therapeutics enhanced the anti-tumor impact. The results show that treatment with cmFPA008, a surrogate antibody targeting mouse CSF1R, resulted in a marked reduction in tumor-associated macrophages (TAMs) and an increase in the relative abundance and activation of cytotoxic CD8+ T cells in preclinical models. In multiple murine tumor models, treatment with cmFPA008 also induced an increase in PD-L1 and significantly enhanced anti-tumor efficacy when combined with an anti-PD1 antibody. In addition, co-administration of cmFPA008 with an agonistic anti-CD40 antibody significantly enhanced tumor suppression compared to either therapy alone. The results provide support for ongoing clinical efforts to evaluate FPA008 as an anti-cancer immunotherapy, particularly in combination with other immuno-oncology therapeutics, including agonists of CD40. Five Prime has initiated a Phase 1a/1b clinical trial with Bristol-Myers Squibb to investigate the efficacy of FPA008 in combination with the anti-PD1 therapeutic OPDIVO (nivolumab) in six tumor types. Five Prime is also developing an agonist antibody to glucocorticoid-induced tumor necrosis factor receptor (GITR) that is expected to enter the clinic in 2017.

Identification of Novel Immune Regulators of Tumor Growth Using RIPPSSM Screening in vivo
Brennan T, Bellovin D, De La Torre J, et al
Friday, November 6, 2015

Five Prime is using its proprietary Rapid In Vivo Protein Production System (RIPPS) screening platform to discover novel protein therapeutics, targets, and drug combinations that can be used in alone or in combinations with other immuno-oncology agents. The authors screened 350 immune cell targets by RIPPS in the CT-26 tumor model and identified proteins that either enhance (potential drug target) or inhibit (potential therapeutic) tumor growth and display favorable changes in TIL (tumor-infiltrating lymphocyte) profiles. Five Prime identified several proteins with novel tumor-inhibiting or tumor-promoting activities. One of these proteins has been evaluated further and displays both strong CD3 infiltrate activity into the tumor and synergistic activity with PD1 blockade. Five Prime is conducting additional studies on each protein in other tumor models and in combination with known immune-modulating drugs.

Identification of a Novel T Cell Co-Inhibitory Receptor and Potential Therapeutic Antibody Target in Oncology
Sallee N, Karasyov A, Bellovin D, et al
Friday, November 6, 2015

In order to identify novel immune regulatory proteins and evaluate their potential as immuno-oncology therapeutic targets, Five Prime screened a subset of its library of human extracellular proteins in vitro for the ability to modulate immune responses. The authors discovered a number of novel T cell co-inhibitors, including one referred to as Novel Co-Inhibitor 1 (or NCI1), which was identified through its inhibitory activity on anti-CD3-stimulated human T cells in an in vitro assay. To confirm its activity, the authors demonstrated that the native protein expressed on an antigen-presenting cell line could inhibit antigen-stimulated CD8+ T cell activation and that blocking antibodies against this protein relieved the inhibition in vitro. This inhibitory activity translated to a murine system and overexpression of the protein in tumor-bearing mice resulted in increased tumor growth. However, blocking NCI1 with an antibody did not have a significant effect on tumor growth as a single agent in in vivo models, and the company is prioritizing other potential targets. The authors will report the further characterization of NCI1.

(Filing, 10-Q, bluebird bio, NOV 5, 2015, View Source [SID:1234508031])

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