(Filing, 10-Q, Regeneron, NOV 4, 2015, View Source [SID:1234507952])

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On November 04, 2015 MacroGenics, Inc. (NASDAQ:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, provided a corporate progress update and reported financial results for the third quarter ended September 30, 2015 (Filing, 8-K, MacroGenics, NOV 4, 2015, View Source [SID:1234507959]).

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"As we strive to create breakthrough biologics and life-changing medicines, the team at MacroGenics was proud to share our progress at our recent R&D Day in New York," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We reported encouraging initial clinical trial results from an ongoing Phase 1 study of enoblituzumab, our Fc-optimized monoclonal antibody that targets B7-H3. We also extended our B7-H3 franchise by advancing MGD009, a DART molecule directed against B7-H3 and CD3, into a Phase 1 study. Furthermore, we recently announced a collaboration with Merck to evaluate margetuximab in combination with Merck’s anti-PD-1 therapy, KEYTRUDA, in patients with advanced gastric cancer. This combination of therapeutics could exploit complementary immune-based mechanisms for targeting tumors and provide an important alternative for patients who do not respond to currently available regimens."

Pipeline Update

Margetuximab is an Fc-optimized monoclonal antibody that targets the human epidermal growth factor receptor 2, or HER2.

Recent highlights include:

· Phase 1b/2 Gastric Cancer Study in Collaboration with Merck: The Company recently announced a collaboration to evaluate the combination of margetuximab with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in a Phase 1b/2 clinical trial in patients with HER2-positive advanced gastric cancer. Trial startup activities are underway, and the Company expects to begin enrolling patients by the first quarter of 2016.

· SOPHIA Study Continues: The Company’s Phase 3 pivotal study in patients with HER2-positive metastatic breast cancer is continuing enrollment. This three-year study is evaluating the efficacy of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy following progression after at least two lines of previous therapy in approximately 530 patients.
B7-H3 Franchise—MacroGenics is developing a portfolio of therapeutics that target B7-H3, a member of the B7 family of molecules involved in immune regulation. The Company’s three programs target B7-H3 through complementary mechanisms of action and take advantage of this target’s broad expression across multiple solid tumor types.

Recent highlights include:

· Enoblituzumab (MGA271): The Company provided an overview of initial data from its ongoing Phase 1 monotherapy clinical study of enoblituzumab, an Fc-optimized monoclonal antibody that targets B7-H3. To date, enoblituzumab has been well tolerated in patients and has shown encouraging, initial single-agent activity, including tumor regression in multiple, heavily pre-treated patients. In addition, evidence of T-cell immunomodulatory function has been observed in patients treated with enoblituzumab. The Company continues to enroll patients in additional monotherapy Phase 1 study cohorts as well as in two combination studies with either ipilimumab or pembrolizumab. Data from the ongoing monotherapy study will be presented in a late-breaking abstract session at the 2015 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting on November 7, 2015.

. Regains European and Other Regional Rights to Enoblituzumab: In October 2015, Les Laboratoires Servier, or Servier, provided notice that it would not be exercising its option under a 2011 agreement to develop and commercialize enoblituzumab in Europe and other countries. Accordingly, the agreement with Servier regarding enoblituzumab has expired and MacroGenics now controls worldwide development and commercialization rights to enoblituzumab. The agreement between MacroGenics and Servier for development of DART molecules is unaffected by this decision.

· MGD009 in Phase 1: MGD009, a Dual-Affinity Re-Targeting, or DART, molecule targeting B7-H3 and CD3, is being tested in a Phase 1 study in patients and is being evaluated across multiple solid tumor types.

· B7-H3 Antibody-Drug Conjugate: The Company continues to evaluate antibody drug conjugate (ADC) molecules to induce direct killing of B7-H3 positive tumor cells.

DART Product Candidates—There are currently five DART molecules in clinical development, including MGD006 (CD123 x CD3, also known as S80880), MGD007 (gpA33 x CD3), MGD011 (CD19 x CD3, also known as JNJ-64052781), MGD010 (CD32B x CD79B) and MGD009 (B7-H3 x CD3). Each of these DART molecules is being evaluated in a Phase 1 clinical study. At its R&D Day, the Company disclosed for the first time two DART molecules that it expects to advance into clinical development in the first half of 2017. These two product candidates include:

· MGD013: MacroGenics is developing an Fc-bearing DART molecule, MGD013, to simultaneously block two immune checkpoint molecules, PD-1 and LAG-3. The company presented promising pre-clinical data demonstrating the activity of a DART molecule with these specificities and expects that this bi-specific combination may be useful for treatment of a wide range of solid tumors and hematological malignancies. Beyond MGD013, MacroGenics is generating and evaluating multiple other candidates that target a range of immune regulatory molecules using its DART platform as well as its Trident platform for generating tri-specific molecules.

· MGD014: MacroGenics presented pre-clinical data on MGD014, a DART molecule that is being developed to eliminate latent HIV infection. MGD014 will be developed under a contract recently awarded by the National Institute of Allergy and Infectious Diseases for up to $24.5 million. This is the first infectious disease DART program planned for clinical testing.

Corporate Update

· Equity Offering: In July, the Company completed an equity offering, raising $141 million in net proceeds, which included exercise of the underwriters’ over-allotment option in full. MacroGenics is using the proceeds of this offering to expand its manufacturing capacity and accelerate development of immune regulatory-based product candidates, including MGD013, advance other research and development programs, in-license or acquire other products or technologies, and for general corporate purposes.

· Partners’ DART Molecules Advance: As previously announced, MacroGenics’ collaboration partner, Janssen Biotech, Inc., paid the Company a $10 million milestone during the third quarter of 2015 after dosing a first patient in an open-label Phase 1 study of MGD011. Also, in October 2015, MacroGenics’ collaboration partner, Boehringer Ingelheim, selected a DART molecule for further pre-clinical development. This triggers a $5 million milestone payment to MacroGenics under an October 2010 agreement to discover, develop and commercialize DART therapeutics.

· Manufacturing Expansion: During the third quarter, the Company signed a lease for additional space with a focus on expanding its commercial manufacturing capabilities.

Third Quarter 2015 Financial Results

· Cash Position: Cash and cash equivalents as of September 30, 2015 were $365.8 million, compared to $157.6 million as of December 31, 2014. The Company expects that its cash balance should fund operations into 2018.

· Revenue: Total revenues, consisting primarily of revenue from collaborative research, were $14.7 million for the three-month period ended September 30, 2015 compared to $18.4 million for the three-month period ended September 30, 2014. Collaborative research revenue includes the recognition of deferred revenue from payments received in previous periods as well as payments received during the quarter.

· R&D Expenses: Research and development expenses were $24.1 million for the three-month period ended September 30, 2015, compared to $18.6 million for the three-month period ended September 30, 2014. This increase was primarily due to preparations for and launch of the margetuximab SOPHIA Phase 3 study, increased activity to prepare for the MGD009 Investigational New Drug (IND) application submission, and costs of other ongoing clinical studies.

· G&A Expenses: General and administrative expenses were $6.0 million for the three-month period ended September 30, 2015, compared to $3.7 million for the three-month period ended September 30, 2014. This increase was primarily due to higher labor-related costs, including stock-based compensation expense and information technology-related expenses.

· Net Loss: Net loss was $15.4 million for the three-month period ended September 30, 2015, compared to net loss of $3.9 million for the three-month period ended September 30, 2014.

· Shares Outstanding: Shares outstanding as of September 30, 2015 were 34,248,240.

(Filing, 10-Q, TetraLogic Pharmaceuticals, NOV 4, 2015, View Source [SID:1234507958])

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On November 4, 2015 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutic candidates that regulate cellular growth and repair, reported a corporate update and reported financial results for the third quarter ended September 30, 2015 (Press release, Acceleron Pharma, NOV 4, 2015, View Source [SID:1234507937]).

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"We made significant progress across our clinical pipeline in the quarter and are poised, with our partner Celgene, to launch two pivotal Phase 3 programs by year-end," said John Knopf, Ph.D., Chief Executive Officer of Acceleron. "We also revealed new clinical data showing unprecedented results with our locally delivered muscle agent, ACE-083. Finally, our discovery team continues to innovate with the introduction of our new IntelliTrap platform, to discover selective and novel compounds targeting the transforming growth factor-beta superfamily of proteins."

Recent Highlights and Current Updates

Development Programs

Hematology

Acceleron and Celgene plan to initiate Phase 3 studies with luspatercept in beta-thalassemia, the BELIEVE trial, and myelodysplastic syndromes (MDS), the MEDALIST trial, by the end of 2015.

Completed enrollment and treatment in the luspatercept Phase 2 dose escalation and expansion studies in MDS and beta-thalassemia.

Treatment continues in Phase 2 long-term extension studies with luspatercept in beta- thalassemia and MDS.
Amended and expanded Phase 2 MDS study. Additional study cohorts have been added to evaluate the effects of luspatercept in lower risk MDS patients that are either erythropoietin-stimulating agent (ESA) treatment naïve or ring sideroblast negative.

Muscle Diseases

Announced initial Phase 1 data on ACE-083, Acceleron’s therapeutic candidate designed to increase muscle mass and strength when delivered locally to targeted muscle groups. Acceleron reported an unprecedented 14.5% mean increase in muscle volume in the injected muscle of the quadriceps. The Company plans to begin a Phase 2 trial in facioscapulohumeral muscular dystrophy (FSHD) in mid-2016.

Presented preclinical data on ACE-083 at the 20th Annual International Congress of the World Muscle Society. ACE-083 produced significant increases in muscle mass of approximately 75% in the injected muscle with no observed effect on either the uninjected contralateral muscle or on whole body mass. Increases in muscle mass were associated with a significant increase in muscle force and power of approximately 40%.

Introduced ACE-2494, Acceleron’s first IntelliTrap molecule, designed for systemic administration to increase muscle mass and strength. In mice, ACE-2494 generated dose dependent increases in muscle mass at a magnitude comparable to the powerful effects of soluble ActRIIB fusion proteins. After 4 weeks of treatment, ACE-2494 (10 mg/kg twice weekly) generated increases in muscle mass ranging from 41% to 87% across different muscle groups. The Company expects to begin clinical studies with ACE-2494 by the end of 2016.

Oncology

FDA granted Fast Track Designation for dalantercept in combination with axitinib for the treatment of patients with advanced renal cell carcinoma (RCC), following treatment with an anti-angiogenic agent.
Presented RCC Phase 2 data showing that the combination of dalantercept and axitinib generated encouraging, progression-free survival after one year. The Company reported the 12-month Kaplan Meier estimate for a progression-free survival rate of 39% for the combination of dalantercept plus axitinib in patients with advanced RCC in Part 1 of the Phase 2 DART study. This compares favorably to the 12-month PFS rate of 25% with axitinib alone.

Nephrology

Acceleron and Celgene will refocus the development of sotatercept in the pre-dialysis chronic kidney disease setting. The Companies plan to meet with regulators in the first half of 2016 to discuss study designs.

Research and Development

Acceleron introduced its new IntelliTrap discovery platform. The IntelliTrap platform is designed to generate dozens of highly selective molecules that optimally target the transforming growth factor-beta superfamily to discover innovative new therapies.

Upcoming Milestones and Events

Initiation of the pivotal Phase 3 clinical trials with luspatercept in MDS and beta-thalassemia is expected by year-end.
Additional luspatercept data from ongoing Phase 2 MDS and beta-thalassemia studies will be presented at the 57th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), December 5-8, 2015 in Orlando, Florida.
ACE-083 Phase 1 clinical data will be presented at the 8th International Conference on Cachexia, Sarcopenia and Muscle Wasting, December 4-6, 2015, in Paris, France.

Clinical and preclinical data will be presented at the American Society of Nephrology Kidney Week, November 3-8, 2015, in San Diego, CA.

Financial Results

Cash Position – Cash, cash equivalents and investments as of September 30, 2015 were $148.1 million. As of December 31, 2014 the company had cash and cash equivalents of $176.5 million. Acceleron expects that its cash, cash equivalents and investments as of September 30, 2015 will be sufficient to fund the Company’s operations into the second half of 2017.

On November 5, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it is providing an update on its late-stage pipeline at an investor event in London, including promising investigational medicines for multiple sclerosis, asthma, haemophilia, eye disease and cancer (Press release, Hoffmann-La Roche , NOV 4, 2015, View Source [SID:1234507963]). In these and other areas, Roche expects as many as seven major read-outs from clinical trials with new molecular entities or line extensions for existing medicines up to the end of 2017, adding to the seven read-outs already achieved in 2015.

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"Thanks to our diversified late-stage portfolio we are well positioned to maintain our leadership in oncology, expand further in the immunology and ophthalmology segments, and potentially offer new treatments to help improve the lives of people with multiple sclerosis and haemophilia," said Daniel O’Day, COO of Roche’s Pharmaceuticals Division. "And we are looking to harness the vast increase in molecular information as the next important step in our efforts to develop even better, more personalised treatment solutions."

In addition to presenting updates on Roche’s most advanced investigational medicines, executives will brief investors and analysts on the company’s strategy, R&D productivity, life-cycle management and approach to new market opportunities. Special breakout sessions will offer insights into Roche’s haematology portfolio, plans to exploit the growing depth and breadth of molecular information for drug discovery and development, and an assessment of the emerging biosimilar landscape.

The presentations will be available via live video webcast or conference call (details at the end of this release).

Addressing unmet need in melanoma, lung cancer and multiple sclerosis

Cotellic is currently undergoing regulatory review in the US and Europe for use in combination with Zelboraf for the treatment of BRAF mutation-positive unresectable metastatic melanoma. Decisions by the FDA and EMA are expected in November and December, respectively. Results from a phase III trial announced by Roche and Exelixis in October showed a statistically significant and clinically meaningful increase in overall survival for patients taking Cotellic plus Zelboraf compared to Zelboraf alone.
Alectinib is an investigational oral medicine for ALK-positive non-small cell lung cancer (NSCLC). After granting Breakthrough Therapy Designation in 2013, the FDA accepted Roche’s US marketing application in September 2015 for priority review, assigning a decision date in March 2016. Roche also filed an EU marketing application in September. A phase III study is comparing alectinib to crizotinib as initial treatment for advanced NSCLC identified as ALK-positive by a companion diagnostic test being developed by Roche.

Ocrelizumab is the first investigational medicine to show positive results in both primary progressive and relapsing forms of multiple sclerosis (PPMS, RMS). Based on pivotal study results, ocrelizumab has the potential to change the way MS is treated. Roche plans to submit data to global regulatory authorities in early 2016 to obtain marketing authorisation for ocrelizumab as a potential new treatment for RMS and first approved treatment for PPMS.

Cancer immunotherapy – preparing a multipronged attack on tumours

Roche’s industry-leading cancer immunotherapy pipeline currently includes eight new molecular entities and some 30 combinations of immunotherapies and targeted cancer medicines being tested in clinical trials.

Atezolizumab is an investigational monoclonal antibody designed to interfere with PD-L1, a protein expressed on tumour cells and tumour-infiltrating immune cells, preventing it from binding to PD-1 and B7.1 on the surface of T cells. By inhibiting PD-L1, atezolizumab may enable the activation of T cells, restoring their ability to detect and attack tumour cells. Roche has initiated a rolling FDA filing for atezolizumab and expects to finalise the data submissions from its phase II trials in the first quarter of 2016 under Breakthrough Therapy Designations for certain types of metastatic bladder and lung cancer. Roche currently has several ongoing phase III studies of atezolizumab alone or in combination with other medicines for various types of lung, bladder, kidney and breast cancer. All studies include the evaluation of a companion test developed by Roche Diagnostics to determine PD-L1 status.

Atezolizumab plus chemotherapy: Based on encouraging early-stage results, Roche is conducting a number of randomised phase III studies to evaluate the benefit of atezolizumab when added to standard chemotherapy in first-line NSCLC. First results are expected in 2017.

Atezolizumab combined with targeted therapies or other cancer immunotherapy agents: Roche is also investigating the potential benefit of combining atezolizumab with targeted medicines such as Avastin, Zelboraf, Cotellic, Tarceva, alectinib or Gazyva, as well as with other cancer immunotherapy agents such as anti-CD40, anti-CSF-1R, anti-OX40, IDO inhibitors or anti-CEA-IL2v FP in a range of cancers.

Aiming for treatment advances for blood cancers, asthma, haemophilia and age-related vision loss

Gazyva/Gazyvaro (obinutuzumab), a glycoengineered monoclonal antibody that binds to CD20 (a protein found only on B cells), is designed to attack and destroy targeted B cells directly and together with the immune system. It is currently approved in more than 50 countries in combination with chlorambucil for previously untreated chronic lymphocytic leukaemia. In October the US FDA accepted for priority review Roche’s supplemental Biologic License Application for Gazyva in the treatment of patients with follicular lymphoma who relapsed after or are refractory to a rituximab-containing regimen, based on results of the phase III GADOLIN study.
Venetoclax is a small-molecule Bcl-2 inhibitor designed to interfere with a process some cancer cells use to survive, thereby promoting programmed cell death, or apoptosis. Ongoing phase II and III studies are investigating venetoclax alone and in combination with other medicines in certain types of chronic lymphocytic leukaemia (CLL), non-Hodgkin’s lymphoma, acute myelogenous leukaemia and multiple myeloma. Earlier this year the US FDA awarded breakthrough designation for venetoclax in the treatment of relapsed or refractory CLL with 17p deletion. Roche’s partner AbbVie has completed a submission to the US FDA for approval of venetoclax, based on the results of a positive phase II trial; AbbVie also plans to submit these data to the EMA and other regulatory authorities around the world for approval consideration.

Lebrikizumab is a first-in-class anti-IL-13 monoclonal antibody under investigation for the treatment of severe uncontrolled asthma. Lebrikizumab has been shown in phase II studies to significantly reduce asthma exacerbation rates and improve lung function in patients with high levels of the biomarker periostin. Phase III trial results are expected in the first half of 2016, with global filings planned soon after. Roche is also investigating lebrikizumab as a potential treatment for other types of lung disease and atopic dermatitis.

ACE910 (factor IXa/X biMAb) is an investigational bispecific antibody specifically engineered to support the interaction between factors IXa and X and hence mimic factor VIII, a protein essential to blood clotting. It is being developed for use in people with haemophilia A, irrespective of inhibitor status. Following encouraging phase I results, Roche plans to initiate a phase III trial of ACE910 in patients with factor VIII inhibitors by the end of 2015, a phase III trial in patients without inhibitors in 2016, and a study in paediatric patients (0–12 years) in 2016.

Lampalizumab (anti-Factor D Fab) is a selective inhibitor of complement-mediated inflammation. It is potentially the first disease-modifying therapy for geographic atrophy (GA), an advanced form of age-related macular degeneration. There are currently no effective therapies approved for GA, a significant cause of irreversible vision loss and blindness in the elderly. A phase II study with lampalizumab was the first to show efficacy in reducing the progression of retinal cell death in GA. Patient recruitment for a phase III program is on track. In addition to efficacy and safety, the studies are assessing the prognostic and predictive roles of a complement factor I profile biomarker. Results are expected in 2017. The US FDA has granted fast-track status to lampalizumab for the treatment of GA secondary to age-related macular degeneration.

Participants at the event are also being briefed on Roche’s ongoing efficiency initiatives in areas such as clinical development, pharmaceutical production and commercialisation, part of the Group’s commitment to optimising use of resources. One result of these efforts has been a doubling of the number of projects in late-stage clinical development since 2010, with no increase in development spend.

Roche experts will also explain the challenges and opportunities of molecular information and its emerging role in drug development, diagnosis, patient selection and treatment monitoring. A key part of Roche’s R&D is directed towards developing new techniques and platforms that can exploit the wealth of molecular data now becoming available in clinical trials and real-world treatment settings. The aim is to use these increasingly detailed data in research and development to help select drug targets and develop new medicines. Molecular information will increasingly be used in routine clinical practice to match patients to the most appropriate treatment and monitor their progress on therapy.

Partners and collaborations
Cotellic (cobimetinib) is being developed in collaboration with Exelixis.
Zelboraf (vemurafenib) is developed in collaboration with Plexxikon, a member of the Daiichi Sankyo Group.
Alectinib (RG7853) is being developed in collaboration with Chugai, a member of the Roche Group.
Venetoclax (Bcl-2 inhibitor, GDC-0199, RG7601) is being developed in collaboration with AbbVie.
ACE910 (RG6013) is being co-developed with Chugai, a member of the Roche Group.