On June 6, 2016 Immunocore, a world-leading biotechnology company developing novel T cell receptor (TCR) based biological drugs to treat cancer, infectious diseases and autoimmune disease, reported that positive data from the first in human, Phase I clinical trial of its lead ImmTAC (Immune mobilising monoclonal TCRs Against Cancer), IMCgp100, was presented in a poster discussion session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on June 5th 2016 (Press release, Immunocore, JUN 6, 2016, View Source [SID:1234513097]).

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IMCgp100 is a first-in-class bi-specific biologic known as a T cell redirector. This ImmTAC binds, with picomolar affinity, to a melanoma associated target, gp100; once bound IMCgp100 redirects all T cells, including non-cancer specific T cells, to kill the cancer cells.

In a presentation entitled: "Safety, Pharmacokinetics and Efficacy of IMCgp100, a First-in-Class Soluble TCR Anti-CD3 Bispecific T Cell Redirector With Solid Tumour Activity: Results From the FIH Study in Melanoma" Mark Middleton MD, Professor of Experimental Cancer Medicine at the University of Oxford, and Principal Investigator for the Study, presented data from the First-In-Human study of IMCgp100 in metastatic melanoma, treating 84 patients in total.

In the study, IMCgp100 showed a favourable safety profile at the established recommended Phase II dose, with prolonged responses observed in both uveal and cutaneous melanoma. Tumour shrinkages in patients with a particularly poor prognosis and those with checkpoint resistant disease were also reported. Some immune mediated toxicities were observed predominantly in the first few doses and were manageable. Rapid T cell infiltration into tumours coinciding with immune activation occurred within days following the first dose in both cutaneous and uveal melanoma patients.

Mark Middleton, Principal Investigator, commented: "These are promising data, we know how to give the drug safely and we are seeing prolonged responses in both uveal and cutaneous melanoma. It is also really encouraging to see tumours shrink in patients with high LDH and/or liver tumour burden. These exciting data strongly support the further development of IMCgp100, in patients with uveal and cutaneous melanoma." 2

Dr. Christina Coughlin, Chief Medical Officer of Immunocore, added: "We are delighted that the data strongly supports the expansion of the IMCgp100 programme into both cutaneous and uveal melanoma Phase II trials and we look forward to progressing our lead programme through further clinical development."

In January 2016 the US Food and Drug Administration (FDA) also granted Orphan Drug Designation to IMCgp100 for the treatment of uveal melanoma. Furthermore, Immunocore has participated in the European Medicines Agency’s (EMA) Adaptive Pathway pilot programme with IMCgp100. Earlier this year, Immunocore initiated a Phase I clinical study of IMCgp100 in patients with uveal melanoma and a combination Phase Ib/II trial with MedImmune’s checkpoint inhibitors durvalumab and tremelimumab.

On June 6, 2016 Moderna Therapeutics, a clinical stage pioneer in the development of messenger RNA (mRNA) Therapeutics and Charles River Laboratories International, Inc. (NYSE: CRL), a leading early-stage contract research organization (CRO), reported a strategic collaboration to support Moderna’s nonclinical discovery and development efforts (Press release, Moderna Therapeutics, JUN 6, 2016, View Source [SID:1234513095]).

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Charles River will be a key partner as Moderna continues to grow and advance its pipeline spanning multiple drug modalities and therapeutic areas, conducting nonclinical activities to progress development candidates through investigational new drug (IND)-enabling studies and into the clinic.

"With ten programs in development across our internal efforts and external collaborations, Moderna continues to generate development candidates and discovery programs at an accelerated pace through our unique mRNA therapeutics research engine. This strategic relationship will help enable the scale, efficiency and speed needed to support the full breadth of discovery programs underway and to continue advancing our development candidates," said Stéphane Bancel, Chief Executive Officer of Moderna. "In particular, this collaboration will allow us to accelerate GLP toxicology study timelines, which will be instrumental as we continue to progress our development candidates into the clinic. Charles River’s expertise across discovery and nonclinical development activities, combined with their familiarity with our novel platform, make them an excellent partner for Moderna. The ability to work with Charles River in its Massachusetts facility will enhance the collaboration, given its proximity to our operations in Cambridge."

Moderna’s pipeline is composed of a series of novel drug modalities, each representing a distinct application of the company’s proprietary core expression mRNA platform to encode proteins that achieve a therapeutic benefit. Moderna’s current modalities include infectious disease vaccines, personalized cancer vaccines, rare disease-associated intracellular/transmembrane liver proteins, intratumoral cancer therapy, and secreted antibodies and proteins. Moderna is leveraging these modalities to advance drugs across a broad spectrum of therapeutic areas via its wholly owned ventures as well as a growing ecosystem of partners.

For nearly 70 years, Charles River has been in the business of providing the research models required in research and development of new drugs, devices and therapies. Over this time, the company has expanded upon its core competency of in vivo biology to develop a diverse portfolio of discovery and safety assessment services, both Good Laboratory Practice (GLP) and non-GLP, which is able to support clients from target identification through preclinical development. Utilizing Charles River’s broad portfolio of products and services, which can be tailored to specific research requirements, enables clients to create a more flexible drug development model which reduces their costs, enhances their productivity and effectiveness, and increases speed to market.

"We are very pleased to enter into this strategic relationship with Moderna," said James C. Foster, Chairman, President and Chief Executive Officer of Charles River Laboratories. "We look forward to employing our unique portfolio and extensive scientific expertise to support Moderna’s nonclinical discovery and development needs and advance its mRNA platform."

On June 6, 2016 Incyte Corporation (Nasdaq:INCY) reported five-year data from the Phase 3 COMFORT-I study evaluating the long-term safety and efficacy of Jakafi (ruxolitinib) in patients with intermediate-2 or high-risk myelofibrosis (MF) (Press release, Incyte, JUN 6, 2016, View Source [SID:1234513060]).

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These follow-up results showed an overall survival (OS) benefit among patients treated with ruxolitinib with a 31 percent reduction in the risk of death (HR=0.69; 95% CI: 0.50, 0.96; P=0.025) compared to patients randomized to placebo. Because the majority of patients on the placebo arm crossed over to receive ruxolitinib therapy (median 41.1 weeks after randomization), these data suggest that earlier treatment with ruxolitinib may be associated with improved long-term survival in patients with intermediate-2 or high-risk MF.

Additionally, over the five-year period, 59 percent (92/155) of patients who continued on treatment with ruxolitinib achieved at least a 35 percent reduction in spleen volume at any given time. The median duration of spleen response was 168.3 weeks. The mean spleen volume reduction from baseline at five years was 37.6 percent for patients who continued on treatment with ruxolitinib. After week 24, hemoglobin and platelet count remained stable through 5 years.

"Nearly, five years after the launch of Jakafi for the treatment of intermediate and high-risk MF, these findings provide important insight into the treatment’s long-term clinical benefits," said Steven Stein, M.D., Incyte’s Chief Medical Officer. "The overall survival benefit observed in the COMFORT-I study, along with sustained reductions in spleen volume, are meaningful for patients with this rare disease who often experience significant, debilitating symptoms, and even mortality, as a result of their disease."

These data are scheduled for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 taking place June 3–7, 2016 in Chicago, Illinois.

"Previous findings from this study and overall survival trends reinforce the benefits of long-term treatment with ruxolitinib in patients with intermediate and high-risk MF. Achieving outcomes such as reduction in spleen volume is critical to the successful management of patients with this chronic and debilitating disease," said Ruben A. Mesa, M.D., FACP, Chair, Division of Hematology & Medical Oncology, Deputy Director, Mayo Clinic Cancer Center, Chair, Arizona Cancer Coalition, and Professor of Medicine.

Results from the COMFORT-I Study
COMFORT-I, a randomized (1:1), double-blind, placebo-controlled Phase 3 study, compared the efficacy and safety of ruxolitinib to placebo in 309 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.
Of the 155 patients randomized to ruxolitinib, 28 percent of patients were still on treatment at the time of this analysis (median follow-up 268 weeks). Of the 111 patients originally randomized to the placebo arm who crossed over to ruxolitinib (median 41.1 weeks after randomization), 25 percent remained on treatment at the time of this analysis (median follow-up 268 weeks).
Overall, 69 (45%) and 82 (53%) deaths were reported in the ruxolitinib and placebo arms, respectively. Median OS has not been reached for patients randomized to receive ruxolitinib.
Adverse events (AEs) were consistent with those reported in previous studies of ruxolitinib and there was no increase in the incidence of AEs with longer exposure to treatment.
COMFORT-I (Abstract #7012) is scheduled for presentation by Dr. Mesa on Monday, June 6, 2016, 8:00–11:30 a.m., E354b Hall A.

About Myelofibrosis (MF)
MF is part of a group of related rare blood cancers known as myeloproliferative neoplasms (MPNs). In MF, a patient’s bone marrow can no longer produce enough normal blood cells, causing the spleen and or liver to enlarge.1 MF is a progressive disease, which leads to bone marrow scarring and significant debilitating disease-related symptoms such as anemia, fatigue, and itching which can result in a poor quality of life.2 Patients with MF have a decreased life expectancy, with an average survival of approximately five to six years.3 The cause of MF is unknown but is linked to genetic mutations—between 50% and 60% of people with MF have a specific mutation of the Janus Kinase 2 gene (JAK2).4
About Jakafi (ruxolitinib)
Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration, for treatment of people with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea.
Jakafi is also indicated for treatment of people with intermediate or high-risk myelofibrosis (MF), including primary MF, post–polycythemia vera MF, and post–essential thrombocythemia MF.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States.
Important Safety Information
Jakafi can cause serious side effects, including:
Low blood counts: Jakafi (ruxolitinib) may cause your platelet, red blood cell, or white blood cell counts to be lowered. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will perform blood tests to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.
Skin cancers: Some people who take Jakafi have developed certain types of non-melanoma skin cancers. Tell your healthcare provider if you develop any new or changing skin lesions.

Increases in Cholesterol: You may have changes in your blood cholesterol levels. Your healthcare provider will do blood tests to check your cholesterol levels during your treatment with Jakafi.

The most common side effects of Jakafi include: low platelet count, low red blood cell counts, bruising, dizziness, headache.
These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had tuberculosis (TB), or have been in close contact with someone who has TB, have or had hepatitis B, have or had liver or kidney problems, are on dialysis, had skin cancer or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change or stop taking Jakafi without first talking to your healthcare provider. Do not drink grapefruit juice while on Jakafi.

Women should not take Jakafi while pregnant or planning to become pregnant, or if breast-feeding.
Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi, is available at www.jakafi.com.

On June 06, 2016 TG Therapeutics, Inc. (NASDAQ:TGTX) reported long term follow-up data of TGR-1202, the Company’s once daily PI3K delta inhibitor, both alone and in combination with TG-1101 (ublituximab), the Company’s novel glycoengineered anti-CD20 monoclonal antibody (Press release, TG Therapeutics, JUN 6, 2016, View Source [SID:1234513057]).

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An integrated analysis of the follow-up data from both studies is being presented today, Monday June 6, 2016 at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), being held in Chicago, Illinois. The poster is being presented from 8:00am – 11:30am CT, and will be reviewed during a discussion session from 1:15pm – 2:45pm CT in Room E354b of McCormick Place.

Michael S. Weiss, the Company’s Executive Chairman and Interim CEO commented on the data, "We continue to be impressed with the safety and activity profile of TGR-1202, especially in combination with TG-1101, together making our proprietary "1303" combination. This data, which includes 3 year follow up, reinforces our belief that TGR-1202 is a differentiated PI3K delta inhibitor from others in the class. The integrated analysis, which includes 165 patients treated with TGR-1202 alone or in combination with TG-1101, demonstrates that the toxicities observed with other PI3K delta inhibitors such as liver toxicity, colitis, pneumonitis and infection are rare with TGR-1202 with discontinuations due to TGR-1202 related AEs occurring in less than 8% of patients. We see this as particularly compelling given the recent setbacks for idelalisib with the closure of a series of randomized studies due to safety concerns. The data presented today provides strong evidence to support the hypothesis that the adverse events seen with idelalisib are not necessarily a class effect." Mr. Weiss continued, "Not only does TGR-1202 appear to have a best-in-class safety and efficacy profile with the convenience of once per day dosing, but also demonstrates that a tolerable PI3K delta inhibitor can induce long-term responses in patients with CLL rivaling BTK inhibitors. However, unlike BTK inhibitors, whose activity has been primarily limited to CLL and MCL, TGR-1202 has also demonstrated significant activity in the larger indications of Follicular Lymphoma and DLBCL. Our UNITY program is designed to highlight the breadth of utility of TG-1303 across a wide range of B-cell malignancies, starting with CLL, and now moving into DLBCL and iNHL to follow soon, and we believe its high level of activity, tolerability and ease of administration will make TG-1303 an important new treatment option for these patients."

The poster, entitled "Long-term follow-up of the PI3K delta inhibitor TGR-1202 demonstrates a differentiated safety profile and high response rates in CLL and NHL: Integrated-analysis of TGR-1202 monotherapy and combined with ublituximab" (Abstract Number: 7512), includes data from 165 patients with relapsed or refractory hematologic malignancies, 90 of which were treated with TGR-1202 and 75 of which were treated with TGR-1202 in combination with TG-1101. Patients were heavily pretreated, with the majority of patients having seen 3 or more prior lines of therapy and 52% (85/165) of patients being refractory to their immediate prior therapy.

Highlights from the poster include:

Safety and Tolerability:

Discontinuations due to TGR-1202 adverse events have been limited (~8%)
Grade 3/4 adverse events commonly associated with PI3K delta inhibitors have been rare, with pneumonia (~5%) and pneumonitis ( < 1.5%), ALT/AST elevations (~3%) and colitis ( < 1.5%), the latter occurring with no apparent association to time on therapy
The two cases of colitis ( < 1.5%) occurred at doses exceeding the Phase 3 dose and did not appear to be time dependent (1000 mg and 1200 mg, at 4 mos. and 24 mos., respectively, after initiating therapy)
165 patients have been treated with TGR-1202 between the two studies with 80 patients on drug for 6+ months, 43 patients for 12+ months, and the longest patients on daily TGR-1202 for 3+ years
Safety and efficacy profile of TG-1303 supports multi-drug combinations including ongoing triple therapy combination studies with novel agents such as ibrutinib, pembrolizumab and bendamustine
Activity:

At the Phase 3 dose of 800mg, the following responses were observed:
88% (14/16) ORR in patients with CLL including 2 CR’s (one of which was a 17p del) plus a PR in an ibrutinib refractory patient
57% (4/7) ORR in patients with DLBCL with compelling activity observed in GCB subtype
53% (9/17) ORR in patients with follicular and marginal zone lymphoma (iNHL)
ORR in iNHL for patients treated at higher doses (1200mg of the initial formulation or ≥600 mg of the micronized formulation), was not only greater with the TG-1303 combination (55%) as opposed to monotherapy with TGR-1202 (41%), but the depth of response was significantly greater with the combination (CR rate of 5% for monotherapy vs. 30% for the TG-1303 combination)
Three (3) Complete Responses were observed in patients with DLBCL treated at higher doses of TGR-1202 in combination with TG-1101, 2 of which were of GCB subtype, supporting our UNITY-DLBCL Phase 2b design
25% ORR in ibrutinib refractory patients, highlighting the challenge of treating patients that break through ibrutinib therapy and the potential risks of initiating ibrutinib therapy early
POSTER PRESENTATION DETAILS

A copy of the poster presentation is available on the Company’s website at www.tgtherapeutics.com, located on the Publications Page, within the Pipeline section.

TG THERAPEUTICS INVESTOR & ANALYST EVENT DETAILS

TG Therapeutics will also host a reception this evening, Monday, June 6, 2016 beginning at 7:00pm CT, with featured presentations beginning promptly at 7:10pm CT. The event will take place at the Peninsula Chicago Hotel in the Avenues Ballroom. This event will be webcast live and will be available on the Events page, located within the Investors & Media section of the Company’s website at www.tgtherapeutics.com, as well as archived for future review. This event will also be broadcast via conference call. In order to access the conference line, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), and reference Conference Title: TG Therapeutics June 2016 Investor & Analyst Event.