On January 11, 2016 FORMA Therapeutics and Cancer Research Technology, reported the formation of a third new virtual Asset Discovery and Development Company (ADDCos) with novel chemical matter targeting an undisclosed deubiquitinating enzyme (DUB) (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234509341]). ADDCos are virtual companies that rapidly advance drug discovery innovations in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

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This achievement is the result of an ongoing long-term initiative between FORMA and Cancer Research Technology, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under the agreement, FORMA is pairing its ultra-efficient drug discovery and early development capabilities with expertise from Cancer Research Technology’s Discovery Laboratories and the exclusive world-class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when aberrantly dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to represent highly attractive discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "The evolution of R&D across a distributed network of diverse scientific disciplines allows FORMA to rapidly and creatively advance research discoveries into clinical candidates."

Keith Blundy, CEO of Cancer Research Technology, said: "This partnership has proven to yield exciting biology and translational outcomes, when pairing complementary skills and capabilities together within a unique business structure. We look forward seeing such research discoveries develop into new medicines offering breakthrough treatments to cancer patients worldwide."

On January 12, 2016 FORMA Therapeutics report the initiation of a Phase 1 study of FT-1101, with the first dose administration in patients with relapsed/refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (Press release, Forma Therapeutics, JAN 12, 2016, View Source [SID:1234509342]). FT-1101 is an oral, structurally distinct and potent pan-inhibitor of the BET (Bromodomain and Extra-Terminal) epigenetic protein family.

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"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome"

"The BET protein family represents an attractive group of therapeutic targets for a variety of liquid and solid tumors, as inhibition of these epigenetic binding proteins allows for selective effects on gene expression. FT-1101 is a novel, oral small molecule targeted against all four BET family members (BRD2, BRD3, BRD4, BRDT)," said John Hohneker, M.D., EVP and Head of Research and Development, FORMA Therapeutics. "The launch of this study is an important step for our team, and we are eager to begin the selection of preferred dosing schedules and potential patient populations in order to optimize activity and tolerability of this novel medicine."

Small molecule inhibition of BET results in down-regulation of the critical oncogene MYC, a master regulator of diverse cell functions critical for cell growth and survival in many cancers. At tolerated doses in human tumor xenograft mouse models, FT-1101 has demonstrated significant anti-tumor activity including tumor regressions.

FT-1101 is part of FORMA’s second global strategic collaboration with Celgene Corporation announced in April 2014. Celgene has obtained an exclusive EU license for FT-1101 in exchange for an undisclosed payment to FORMA. Under the terms of the collaboration agreement, FORMA will advance the FT-1101 program through Phase 1, and Celgene will be responsible to fund and execute further global clinical development.

"I am impressed with the inhibition profile and differentiated preclinical activity of FT-1101, and we aim to move quickly to define the safety, tolerability and initial activity of this novel BET inhibitor in acute leukemias and myelodysplastic syndrome," said Guillermo Garcia-Manero, M.D., lead clinical investigator for FT-1101 at The University of Texas MD Anderson Cancer Center, Houston, TX, and Professor, Department of Leukemia, Division of Cancer Medicine.

On January 12, 2016 FORMA Therapeutics and Cancer Research Technology reported the formation of a third new virtual Asset Discovery and Development Company (ADDCos) with novel chemical matter targeting an undisclosed deubiquitinating enzyme (DUB) (Press release, Cancer Research Technology, DEC 12, 2016, View Source [SID1234523189]). ADDCos are virtual companies that rapidly advance drug discovery innovations in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

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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

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This achievement is the result of an ongoing long-term initiative between FORMA and Cancer Research Technology, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under the agreement, FORMA is pairing its ultra-efficient drug discovery and early development capabilities with expertise from Cancer Research Technology’s Discovery Laboratories (CRT-DL) and the exclusive world-class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to represent highly attractive discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "The evolution of R&D across a distributed network of diverse scientific disciplines allows FORMA to rapidly and creatively advance research discoveries into clinical candidates."

Keith Blundy, CEO of Cancer Research Technology, said: "This partnership has proven to yield exciting biology and translational outcomes, when pairing complementary skills and capabilities together within a unique business structure. We look forward seeing such research discoveries develop into new medicines offering breakthrough treatments to cancer patients worldwide."

On January 11, 2015 Celgene Corporation (NASDAQ:CELG) reported a business update as well as its preliminary 2015 results and financial outlook for 2016 at the 34th Annual J.P. Morgan Healthcare Conference (Press release, Celgene, JAN 11, 2016, View Source [SID:1234508741]). In 2016, net product sales are expected to be approximately $10.5 billion to $11.0 billion, a 17 percent increase year-over-year, based on the mid-point of the range. The negative impact of foreign exchange on net product sales is expected to be approximately $120 million in 2016. For the full-year 2016, REVLIMID net sales are expected to be in the range of $6.6 billion to $6.7 billion. Adjusted diluted earnings per share (EPS) for the full-year 2016 is expected to be in the range of $5.50 to $5.70, a 19 percent increase year-over-year, based on the mid-point of the range. Based on U.S. Generally Accepted Accounting Principles (GAAP), diluted EPS is expected to be in the range of $4.26 to $4.64.

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"In 2015, we delivered a strong year operationally and commercially with eight regulatory approvals, the acquisition of Receptos and significant acceleration of our pipeline," said Bob Hugin, Celgene’s Chairman and Chief Executive Officer. "The momentum in our operations and the advancement of our pipeline gives us confidence in our 2020 targets and beyond."

Preliminary 2015 Financial Results Year-Over-Year (Unaudited)

Total net product sales are expected to be approximately $9,160 million, up 21 percent year-over-year. Fourth quarter of 2015 net product sales are expected to be approximately $2,540 million.
REVLIMID: $5,801 million, 16 percent year-over-year increase
ABRAXANE: $967 million, 14 percent year-over-year increase

POMALYST/IMNOVID: $983 million, 45 percent year-over-year increase
OTEZLA: $472 million in the first full year of sales

Adjusted operating margin is expected to be approximately 52 percent for the full year, up 140 basis points (bps) year-over-year. GAAP operating margin is expected to be approximately 24 percent, a decrease from 33 percent in the prior year, primarily due to increased upfront payments to collaboration partners in 2015

Adjusted diluted EPS is expected to be approximately $4.71, a 27 percent year-over-year increase, and reflects $0.14 dilution associated with the Receptos Inc. transaction. GAAP diluted EPS is expected to be in the range of $1.89 to $1.99, and reflects $0.40 dilution associated with the Receptos Inc. transaction

For the fourth quarter of 2015 adjusted diluted EPS is expected to be approximately $1.18, including a $0.07 impact from a $70 million milestone achieved by OncoMed Pharmaceuticals Inc. during the quarter. GAAP diluted EPS is expected to be in the range of $0.63 to $0.73

Certain activities involved in determining the audited results for the fiscal year ended December 31, 2015 are in process and could result in the final reported audited results being different from the unaudited results noted in this press release. Please see the attached Reconciliation of Estimated/Projected GAAP to Adjusted (Non-GAAP) Measures for further information.

Celgene Expects Strong Product Sales and Earnings Growth in 2016

Total net product sales of $10.5 billion to $11.0 billion, an increase of 17 percent year-over-year based on the mid-point of the range and includes a negative impact from foreign exchange of approximately $120 million
REVLIMID net sales in the range of $6.6 billion to $6.7 billion, an increase of 15 percent year-over-year based on the mid-point of the range

Adjusted operating margin of approximately 53.5 percent after investments across the entire organization, a 150 bps improvement over 2015. GAAP operating margin is expected to be approximately 42 percent

Adjusted diluted EPS in the range of $5.50 to $5.70, an increase of approximately 19 percent year-over-year based on the mid-point of the range. GAAP diluted EPS is expected to be in the range of $4.26 to $4.64
Fully diluted share count in 2016 of approximately 825 million

Please see the attached Reconciliation of Estimated/Projected GAAP to Adjusted (Non-GAAP) Measures for further information.

Affirming Expected 2020 Long-term Financial Targets

2020 total net product sales to exceed $21 billion
Hematology franchise to exceed $14.8 billion
Oncology franchise to exceed $2.2 billion
I&I franchise to exceed $4 billion
Adjusted diluted EPS to exceed $13.00
Fully diluted share count of approximately 830 million
2016 Expected Operational Milestones

Hematology/Oncology

Regulatory Submissions/Decisions

Submission for REVLIMID as maintenance after stem-cell transplant in newly diagnosed multiple myeloma (NDMM) in the U.S. and Europe
Submission of renal impairment data for label update for POMALYST/IMNOVID in relapsed/refractory multiple myeloma (RRMM) in the U.S. and Europe
Submission of ABRAXANE for early-stage breast cancer in Europe
Decision by the Committee for Medicinal Products for Human Use (CHMP) on the submission of REVLIMID for relapsed/refractory mantle cell lymphoma in Europe

Clinical Data

Data from the phase III REMARC trial with REVLIMID as maintenance in diffuse large B-cell lymphoma (DLBCL)
Data from the phase III cooperative group ETNA trial with ABRAXANE as neoadjuvant therapy in HER2-negative high-risk breast cancer
Data from the CLL-002 CONTINUUM trial with REVLIMID as maintenance in relapsed/refractory chronic lymphocytic leukemia (CLL)

Data from a phase II trial with CC-122 in non-Hodgkin’s lymphoma (NHL)
Data from phase II trials with motolimod (VTX-2337) in squamous cell carcinoma of the head and neck and ovarian cancer in collaboration with partner VentiRx
Data from the phase II tnAcity trial with ABRAXANE in triple-negative breast cancer

Trial Enrollment

Complete enrollment in the phase III AUGMENT trial with REVLIMID in relapsed/refractory follicular lymphoma
Complete enrollment in the phase III apact (PANC-003) trial with ABRAXANE as adjuvant therapy in surgically resected pancreatic cancer
Complete enrollment in a phase II trial with CC-486 in combination with pembrolizumab in locally advanced or metastatic non-small cell lung cancer

Trial Initiations

Initiate enrollment in a phase I trial of B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy in RRMM in collaboration with partner bluebird bio
Initiate enrollment in six trials in the FUSIONTM program with durvalumab in NDMM, RRMM, NHL, myelodysplastic syndromes and acute myeloid leukemia with partner AstraZeneca/MedImmune
Initiate phase II combination studies with AG-221 and AG-120 in frontline AML in collaboration with partner Agios

I&I

Regulatory Submissions/Decisions

Submission of OTEZLA for psoriasis in Japan

Clinical Data

Long-term radiographic data from the POSTURE (AS-001) trial with OTEZLA in ankylosing spondylitis
Data from the phase III PSA-006 trial with OTEZLA in patients with active psoriatic arthritis who are biologic-naïve
Data from the phase III PSOR-011 trial with OTEZLA in Japanese patients with psoriasis
Data from a pharmacokinetic comparability study to support registration of the OTEZLA once-daily formulation
Data from a phase II trial with OTEZLA in atopic dermatitis
Data from a phase II trial with CC-220 in systemic lupus erythematosus
Data from a phase II trial with RPC-4046 in eosinophilic esophagitis

Trial Enrollment

Complete enrollment in the phase III RELIEFTM (BCT-002) trial with OTEZLA in active Behçet’s disease
Complete enrollment in a phase II trial with OTEZLA in ulcerative colitis
Complete enrollment in the phase II STEPSTONE trial with ozanimod in Crohn’s disease
Research and Early Development

File eight Investigational New Drug (IND) applications
Advance at least two compounds to mid-to-late stage development

Management Changes

On January 8, the Company announced changes to our Research & Early Development organizational structure, which will leverage our strong foundation and drive the rapid advancement of next generation landmark therapies. Tom Daniel, MD, President, Research and Early Development is appointed to Chairman of Celgene Research. Tom, who has been instrumental in building our broad and deep development engine, will oversee strategic initiatives and investments in our research and collaboration portfolio. Rupert Vessey, MA, BM BCh, FRCP, DPhil succeeds Tom Daniel as President, Research and Early Development. Rupert joined Celgene a year ago bringing great insight and leadership to the evolution of our discovery and development strategies in inflammation and immunology as well as in hematology and oncology. Rupert is responsible for leading the execution of discovery and development programs across our portfolio ensuring Celgene capitalizes on the potential of its internal and partnered opportunities. Rob Hershberg, MD, PhD is promoted to Chief Scientific Officer (CSO) and will lead the expansion of our scientific platforms and discovery capabilities. Rob joined Celgene in August 2014 and has led the development of our immuno-oncology efforts, helping to engineer several key collaborations and partnerships.

Q4 and Full year 2015 Conference Call and Webcast Information

Celgene will host a conference call to discuss the fourth quarter and full-year of 2015 operational and financial performance on Thursday, January 28, 2016, 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 January 28, 2016, until midnight ET February 4, 2016. 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 11177982.

On January 11, 2016 Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) (Cyclacel or the Company) reported 2015 achievements and provided an outline of the Company’s key business objectives for 2016 (Press release, Cyclacel, JAN 11, 2016, View Source [SID:1234508742]). These will be highlighted at the Company’s presentation during the Biotech Showcase 2016 Conference at 9:30 a.m. PST, Monday, January 11, 2016, at the Parc 55 Wyndham Hotel – Union Square at 55 Cyril Magnin Street in San Francisco.

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"During 2015, we continued to follow-up patients in SEAMLESS, our Phase 3 clinical trial evaluating sapacitabine in the front-line treatment setting of elderly patients with acute myeloid leukemia, or AML," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "Approximately 7% of prespecified events remain to be observed before we can unblind the randomization code and report top-line results. We anticipate this happening by the end of the first half of 2016. At that point, we will analyze available data and determine submissibility to regulatory authorities. We also continued to follow patients in our Phase 1 trial of sapacitabine and seliciclib in patients with advanced solid tumors. Based on observations to date, we are extending the trial into a selected population of patients with breast cancer who are positive for BRCA mutations. Finally, we advanced CYC065, our second-generation CDK2/9 inhibitor, into a Phase 1, first-in-human study. Based on our preclinical data, we have determined the mechanistic rationale for the clinical development of CYC065 in certain hematological and solid tumor indications. We believe that 2016 may prove to be an important year for Cyclacel and we look forward to keeping you apprised of developments as the year unfolds."

2015 Achievements

Drug Development

Sapacitabine in SEAMLESS, pivotal Phase 3 study as first-line treatment in elderly patients with AML:

Continued follow-up and treatment of patients of this fully enrolled study.
7% of events remain before reporting topline results and mature data analysis.
Submitted to the European Medicines Agency (EMA) a Paediatric Investigation Plan application for sapacitabine.

Sapacitabine and seliciclib in Phase 1 study in patients with advanced solid tumors

Continued to follow patients treated with the all-oral combination of the CDK2/9 inhibitor seliciclib and sapacitabine in a Phase 1 trial in patients with advanced solid tumors. A breast cancer patient with BRCA mutations has been administered more than 70 cycles of the combination and continues on treatment.

Cyclin Dependent Kinase (CDK) Inhibitor Programs

Dosed the first patients in a Phase 1 trial of CYC065, the Company’s second-generation CDK2/9 inhibitor, to evaluate the safety, tolerability and pharmacokinetic profile of CYC065 in solid tumor and lymphoma patients.

Presented preclinical data on the molecular rationale and therapeutic potential in both hematologic and solid tumors of CYC065 at several medical conferences including the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2015, the Society of Hematologic Oncology (SOHO) 2015 Annual Meeting, the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference and the San Antonio Breast Cancer Symposium (SABCS). The data show that:
CYC065 may reverse drug resistance associated with addiction of cancer cells to cyclin E, the partner protein of CDK2.
CYC065 may also inhibit CDK9-dependent oncogenic and leukemogenic pathways, including malignancies driven by certain oncogene and MLL rearrangements. MLL gene status and levels of Bcl-2 family proteins correlated with sensitivity of AML cell lines to CYC065.

CYC065’s anticancer activity presents an opportunity for patient stratification and combinations with anti-leukemic agents.
CYC065 was also effective against uterine cancer cells including those resistant to chemotherapy and was especially potent in uterine cancer cells in which cyclin E was amplified or overexpressed.

CYC065 could be active in triple-negative breast cancer.

First patients dosed in a Phase 2 investigator-sponsored trial (IST) evaluating seliciclib in patients with Cushing’s disease.
Presented preclinical data at the 4th Neuroblastoma Symposium in Newcastle Upon Tyne, UK demonstrating that CYC065 prolongs survival in MYCN-addicted neuroblastoma models.

Corporate Developments

Raised gross proceeds of $10 million from a public offering of common stock.
Entered into a Controlled Equity OfferingSM Sales Agreement with Cantor Fitzgerald & Co., as sales agent ("Cantor"), under which the Company may, from time to time, sell shares of its common stock having an aggregate offering price of up to $8.35 million through Cantor.

Entered into a license and supply agreement with ManRos Therapeutics regarding the development of oral seliciclib for the treatment of cystic fibrosis.

2016 Key Upcoming Business Objectives

Sapacitabine in SEAMLESS:

Continue follow-up of patients until the requisite number of events occur, which is anticipated by the end of the first half of 2016.
Report top-line results.

Following analysis of the mature data set determine submissibility to regulatory authorities for marketing approval.
Progress a Paediatric Investigation Plan for sapacitabine with the European Medicines Agency.
Sapacitabine in myelodysplastic syndromes (MDS):

Initiate a Phase 1/2 trial of sapacitabine in combination with other agents to determine safety and tolerability.
Plan a Phase 2 randomized controlled trial (RCT) of sapacitabine in combination with other agents following review of all relevant clinical data with mature follow-up.

Sapacitabine and seliciclib in Phase 1 study in patients with advanced solid tumors:

Initiate expansion of the Phase 1 study in a breast cancer patient population enriched for BRCA mutations.
Report updated Phase 1 data.

Cyclin Dependent Kinase (CDK) Inhibitor Programs

Report top-line results of the CYC065 Phase 1 trial in solid tumor and lymphoma patients.

Report data from seliciclib ISTs when available.

For the live and archived webcast of the Company’s presentation at the Biotech Showcase 2016 San Francisco conference, please visit the Corporate Presentations page on the Cyclacel website at www.cyclacel.com. The webcast will be archived for 90 days and the audio replay for seven days.