On May 27, 2016 Jubilant Biosys Ltd ("Jubilant Biosys"), a subsidiary of Jubilant Life Sciences Ltd, and Checkpoint Therapeutics, Inc. ("Checkpoint"), a subsidiary of Fortress Biotech, Inc. (NASDAQ: FBIO), reported the signing of an exclusive, worldwide license agreement under which Jubilant Biosys will out‐license to Checkpoint a family of patents covering compounds that inhibit BRD4, a member of the BET (Bromodomain and Extra Terminal) domain for cancer treatment (Press release, Fortress Biotech, MAY 27, 2016, View Source [SID:1234512842]).

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The deal includes an up‐front payment of US $2 million and contingent preclinical, clinical and regulatory payments including commercial milestonestotalling up to US $180 million. Jubilant Biosys will also receive research funding and royalty payments on successful commercialization of the compounds. Checkpoint will assume all further preclinical, clinical development and commercialization responsibilities.

The field of epigenetics as a treatment for cancer is a rapidly evolving area of focus for the pharmaceutical and biotech industry. Both parties believe that by working together to further develop these compounds, they will better be able to move towards bringing a product to market that will greatly improve the lives of patients.

Mr. Shyam S. Bhartia, Chairman and Mr. Hari S. Bhartia, Co‐Chairman and Managing Director of Jubilant Life Sciences, commented, "The Drug Discovery business vertical under Jubilant Biosys and Jubilant Chemsys has acquired many years of extensive expertise and knowledge working with large pharma and biotech companies. Jubilant had decided to make strategic investments in proprietary drug discovery of small molecules with an intent to out‐licence the same for upfront payments and phased milestone payments/royalties. This agreement represents our first out‐licensing deal which is a testament to our investment in innovation in the pharmaceutical business."

James F. Oliviero, III, President and CEO of Checkpoint stated, "We are very pleased to be partnering with Jubilant Biosys to license a family of patents covering compounds that inhibit BRD4 for cancer treatment.  This agreement enhances our current product portfolio of immuno‐oncology and targeted anti‐cancer agents. BET inhibitors have generated significant excitement within the oncology community and Jubilant’s asset provides us with additional opportunities to explore proprietary combinations and treatment options for patients. We appreciate Jubilant entrusting our organization to continue development of their exciting technology." 

On May 27, 2016 TG Therapeutics, Inc. (Nasdaq:TGTX), reported that as part of a broader agreement with Jubilant Biosys ("Jubilant"), an Indian biotechnology company, TG Therapeutics entered into a sub-license agreement with Checkpoint Therapeutics, Inc. ("Checkpoint"), a Fortress Biotech company, to develop and commercialize Jubilant’s novel BET inhibitor program in the field of hematological malignancies (Press release, TG Therapeutics, MAY 27, 2016, View Source [SID:1234512830]).

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Checkpoint will develop and commercialize these small molecule inhibitors in solid tumors. The BET inhibitor program is the subject of an exclusive, worldwide license agreement pursuant to which Checkpoint in-licensed from Jubilant a family of patents covering compounds that inhibit BRD4, a member of the BET (Bromodomain and Extra Terminal) domain for cancer treatment.

Under the terms of the agreement, TG Therapeutics will pay an up-front licensing fee of $1 million and make additional payments contingent on certain preclinical, clinical, and regulatory milestones, including commercial milestones totaling up to approximately $177 million and a single-digit royalty on net sales. TG Therapeutics will also provide funding to support certain targeted research efforts at Jubilant Biosys.

Mr. Michael S. Weiss, Executive Chairman, Interim CEO and President stated, "We are very excited to add this BET inhibitor program to our growing portfolio of agents targeting hematological malignancies. BET inhibitors have shown early promise in the treatment of relapsed and refractory Non-Hodgkin lymphomas, which remains a significant area of unmet medical need. There is emerging preclinical data showing BET inhibitors may enhance the activity of immuno-oncology agents, such as anti-PD-1/PD-L1 antibodies, providing multiple opportunities for us to combine this novel mechanism within our portfolio. Epigenetic targeted agents, especially BET inhibitors, have been an area of great interest of ours for some time and are particularly attractive to us because of their effects on c-Myc driven tumors, like aggressive GCB-subtype DLBCL, an area we have seen early activity with TGR-1202 and our proprietary combination referred to as TG-1303. We want to thank our collaborators at Checkpoint for introducing us to this opportunity." Mr. Weiss continued, "As we prepare to launch our registration directed studies in DLBCL and Follicular Lymphoma, we continue to look toward next steps in the evolution of patient care and believe the best outcome will be achieved only through the combination of multiple novel agents."

On May 27, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a negative opinion, recommending against the authorization of NINLARO (ixazomib) capsules, an oral proteasome inhibitor for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Takeda, MAY 27, 2016, View Source [SID:1234512829]). Takeda intends to appeal this opinion and request a re-examination by the CHMP.

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"We are disappointed by the CHMP’s opinion. With the support of European key medical experts, we will continue our efforts working closely with the CHMP to make NINLARO – the first oral proteasome inhibitor – available for patients in Europe," said Christophe Bianchi, M.D., President, Takeda Oncology. "Despite recent progress, myeloma remains an intractable disease, and patients suffering from multiple myeloma and their treating physicians need more options to improve outcomes. We stand behind the TOURMALINE-MM1 trial data, which were recently published in the New England Journal of Medicine and demonstrated a significant extension in progression-free survival for NINLARO + lenalidomide and dexamethasone vs. placebo + lenalidomide and dexamethasone and a favorable benefit-risk profile."

"After years of treating patients, I have yet to see two people whose diseases are exactly alike. The diversity of patients with multiple myeloma demands a wide range of innovative treatment options that offer efficacy, tolerable safety profiles and convenience, which are especially important benefits for elderly populations," said Philippe Moreau, M.D., University of Nantes, France. "In Europe, where no oral proteasome inhibitor is available, NINLARO would fill a noticeable void and enable the first all-oral triplet combination therapy for patients with relapsed or refractory multiple myeloma."

NINLARO was approved by the U.S. Food and Drug Administration (FDA) in November 2015 following a priority review. In the U.S., NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. The FDA approval of NINLARO marked the first global regulatory approval of ixazomib. Takeda also has submitted applications for approval of ixazomib to additional regulatory authorities around the world. In addition to the TOURMALINE-MM1 trial that is forming the basis of these global regulatory submissions in relapsed and refractory multiple myeloma, ixazomib is being investigated in a number of other multiple myeloma treatment settings.

There will be no significant impact to Takeda’s fiscal year 2016 financials due to the CHMP opinion.

About NINLARO (ixazomib)
NINLARO (ixazomib) is an investigational oral proteasome inhibitor which is being studied in multiple myeloma and systemic light-chain (AL) amyloidosis. It was the first oral proteasome inhibitor to enter Phase 3 clinical trials and to receive approval.

Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory systemic light-chain (AL) amyloidosis, a related ultra orphan disease, in 2014.

The comprehensive ixazomib clinical development program, TOURMALINE, further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. TOURMALINE includes a total of five ongoing pivotal trials – four investigating every major multiple myeloma patient population and one in light-chain amyloidosis:

TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma
TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)
TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT
TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis
In addition to the TOURMALINE program, a large number of investigator initiated studies are evaluating ixazomib for patients globally.

About Multiple Myeloma

Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of monoclonal plasma cells, or myeloma cells, becomes cancerous and multiplies. These malignant plasma cells have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anemia. Multiple myeloma is a rare form of cancer, with approximately 39,000 new cases in the EU and 114,000 new cases globally per year.

Important Safety Information (U.S.)

WARNINGS AND PRECAUTIONS

Thrombocytopenia has been reported with NINLARO. During treatment, monitor platelet counts at least monthly, and consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines. Adjust dosing as needed. Platelet nadirs occurred between Days 14-21 of each 28-day cycle and recovered to baseline by the start of the next cycle.
Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting, were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for severe symptoms.
Peripheral Neuropathy (predominantly sensory) was reported with NINLARO. The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed.
Peripheral Edema was reported with NINLARO. Monitor for fluid retention. Investigate for underlying causes when appropriate and provide supportive care as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms.
Cutaneous Reactions: Rash, most commonly maculo-papular and macular rash, was reported with NINLARO. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modification.
Hepatotoxicity has been reported with NINLARO. Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly during treatment and adjust dosing as needed.
Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women should be advised of the potential risk to a fetus, to avoid becoming pregnant, and to use contraception during treatment and for an additional 90 days after the final dose of NINLARO.
ADVERSE REACTIONS

The most common adverse reactions (≥ 20%) in the NINLARO regimen and greater than the placebo regimen, respectively, were diarrhea (42%, 36%), constipation (34%, 25%), thrombocytopenia (78%, 54%; pooled from adverse events and laboratory data), peripheral neuropathy (28%, 21%), nausea (26%, 21%), peripheral edema (25%, 18%), vomiting (22%, 11%), and back pain (21%, 16%). Serious adverse reactions reported in ≥ 2% of patients included thrombocytopenia (2%) and diarrhea (2%).

SPECIAL POPULATIONS

Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.
Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. NINLARO is not dialyzable.
Lactation: Advise women to discontinue nursing while on NINLARO.
DRUG INTERACTIONS: Avoid concomitant administration of NINLARO with strong CYP3A inducers.

Please see NINLARO full U.S. Prescribing Information: View Source

On May 27, 2016 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the extension of the current conditional approval of ADCETRIS (brentuximab vedotin) and recommended its approval for the treatment of adult patients with CD30+ Hodgkin lymphoma at increased risk of relapse or progression following autologous stem cell transplantation (ASCT) (Press release, Takeda, MAY 27, 2016, View Source [SID:1234512828]).

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On average 50 percent of Hodgkin lymphoma patients relapse after ASCT and those patients with additional risk factors can be at even higher risk of relapse. ADCETRIS after ASCT is a new treatment paradigm based on the largest randomized study ever conducted in relapsed or refractory Hodgkin lymphoma. The AETHERA Phase 3 trial is the first completed study that has explored consolidation treatment immediately following ASCT as a way of extending the effect of transplant for prevention of relapse among people with Hodgkin lymphoma. The use of ADCETRIS in this setting may provide a meaningful treatment option where none currently exist for patients.

"While ASCT is the standard of care following failure of frontline chemotherapy in Hodgkin lymphoma, we know that many patients will unfortunately see their disease return. Early eradication of residual disease through treatment with ADCETRIS has the highest chance of preventing the disease from returning in these patients," said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. "This opinion, in addition to the recent five year overall survival data in relapsed or refractory Hodgkin lymphoma, further establishes the role of ADCETRIS in improving outcomes for patients. We look forward to the European Commission’s authorization of this new indication and bringing this medicine to physicians and patients in the European Union."

The CHMP positive opinion for ADCETRIS will now be reviewed by the European Commission (EC). If the CHMP recommendation is formally adopted by the EC, which has the authority to approve medicines for the European Union (EU), ADCETRIS will be approved for marketing of this indication in the 28 member states of the EU, Norway Liechtenstein and Iceland.

This opinion is based on the results of the Phase 3 AETHERA study. The AETHERA trial met its primary endpoint with ADCETRIS (plus best supportive care) treatment resulting in a statistically significant improvement in progression-free survival (PFS) versus placebo (plus best supportive care) as assessed by an independent central review committee (hazard ratio=0.57; p-value=0.001), which equates to a 75 percent improvement in PFS. PFS was assessed after a minimum of two years post initiation of treatment for all study patients. An updated analysis conducted after three years of follow up showed sustained PFS improvement (per Independent Review Facility; HR=0.58; 95%CI (0.41,0.81). A pre-specified interim analysis of overall survival showed no statistically significant difference between the treatment arms. The safety profile of ADCETRIS in the AETHERA trial was generally consistent with the existing prescribing information.

About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

About ADCETRIS
ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing proprietary technology by Seattle Genetics. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). In January 2016, the European Commission approved a Type II variation to include data on the retreatment of adult patients with Hodgkin lymphoma or sALCL who previously responded to ADCETRIS and who later relapse. ADCETRIS has received marketing authorization by regulatory authorities in more than 60 countries. See important safety information below.

ADCETRIS is being evaluated broadly in more than 45 ongoing clinical trials, including the Phase 3 ALCANZA trial in CD30+ cutaneous T cell lymphoma (CTCL) and two additional Phase 3 studies, one in frontline classical Hodgkin lymphoma (ECHELON-1) and one in frontline CD30+ mature T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-expressing malignancies.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.