On June 14, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that DYNAMO, a registration-focused Phase 2 monotherapy study evaluating the efficacy and safety of duvelisib, an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with refractory indolent non-Hodgkin lymphoma (iNHL) met its primary endpoint of overall response rate (Press release, Infinity Pharmaceuticals, JUN 14, 2016, View Source [SID:1234513312]). In the study, duvelisib demonstrated an overall response rate (ORR) of 46 percent, all of which were partial responses, among 129 patients with iNHL. The majority of reported side effects were reversible and clinically manageable.

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"While the DYNAMO study met its primary endpoint, we hoped that treatment with duvelisib as a monotherapy would have provided a larger clinical benefit for patients with advanced indolent non-Hodgkin lymphoma, a difficult-to-treat disease," stated Adelene Perkins, president and chief executive officer at Infinity. "We plan to seek feedback from the U.S. Food and Drug Administration to determine our next steps with respect to duvelisib in indolent non-Hodgkin lymphoma."

In addition, Infinity and AbbVie are in ongoing, collaborative discussions to explore next steps for the parties’ collaboration. Pending the resolution of these business discussions, AbbVie and Infinity have also agreed to pause the AbbVie-sponsored Phase 1b/2 study evaluating duvelisib in combination with venetoclax.

Infinity is also undertaking a strategic restructuring that will close down its discovery research organization, impacting 46 members of the Infinity team, or 21 percent of the workforce.

"This restructuring is a necessary step to preserve financial resources as we explore options for duvelisib and the advancement of IPI-549, our second clinical program," stated Adelene Perkins, president and chief executive officer. "These were very difficult decisions that were undertaken, and I would like to personally express my deep appreciation to the very talented and dedicated Citizen-Owners impacted by the restructuring for their tremendous contributions to Infinity."

Infinity expects to provide updated 2016 financial guidance following the resolution of these strategic activities. The previous financial guidance for 2016 should no longer be relied upon.

DYNAMO Study Details
DYNAMO, a Phase 2 single-arm study, evaluated the efficacy and safety of duvelisib (25 mg twice daily) as a monotherapy in 129 patients with follicular lymphoma (n = 83), small lymphocytic lymphoma (n = 28) or marginal zone lymphoma (n = 18) whose disease has progressed and who are refractory to rituximab and to either chemotherapy or radioimmunotherapy. The primary endpoint of the study was overall response rate as assessed by an independent review committee.

In the study, the overall response rate was 46 percent, all of which were partial responses. The overall response rate was 41 percent among patients with follicular lymphoma, 68 percent among patients with small lymphocytic lymphoma and 33 percent among patients with marginal zone lymphoma.

In the overall study population, the majority of side effects were reversible and clinically manageable. The most common ≥ Grade 3 side effects that occurred in at least 10 percent of patients in the study were neutropenia (28 percent), diarrhea (15 percent), thrombocytopenia (13 percent) and anemia (12 percent). Twenty percent of patients experienced ≥ Grade 3 infection.

Infinity expects to submit data from the DYNAMO study for presentation at an upcoming scientific conference.

Conference Call Information
Infinity will host a conference call today, June 14, 2016, at 8:30 a.m. ET to discuss the duvelisib data, the restructuring and other corporate developments. A live webcast of the conference call can be accessed in the Investors/Media section of Infinity’s website at www.infi.com. To participate in the conference call, please dial 1-877-316-5293 (domestic) and 1-631-291-4526 (international) five minutes prior to start time. The conference ID number is 33224813. An archived version of the webcast will be available on Infinity’s website for 30 days.

About NHL
Non-Hodgkin lymphoma (NHL) is the seventh leading site of new cancer cases among men and women.1 Follicular Lymphoma (FL) is the most common indolent (slow growing) form of non-Hodgkin lymphoma (NHL), and accounts for about 22 percent of all newly diagnosed cases of NHL worldwide.1 Follicular lymphoma is considered incurable2, and the majority of FL patients diagnosed and treated will experience a pattern of relapse after sequential treatment regimens.3

About Duvelisib
Duvelisib is an investigational dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, two proteins that are known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.4,5,6 AbbVie and Infinity Pharmaceuticals, Inc. are jointly researching and developing duvelisib in various cancer types.

Duvelisib is being evaluated in several studies, including a Phase 3 study in combination with other agents in patients with previously treated follicular lymphoma7 and a Phase 3 study in patients with relapsed/refractory chronic lymphocytic leukemia8. Duvelisib is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.

On June 14, 2016 AMRI (NASDAQ: AMRI) reported that its Buffalo, N.Y. site has been selected to participate as a Dedicated Chemical Biology Consortium (CBC) Center for the Experimental Therapeutics (NExT) Program, centered at the Frederick National Laboratory for Cancer Research (Press release, Albany Molecular Research, JUN 14, 2016, View Source [SID:1234513311]).

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The Frederick National Lab, sponsored by the National Cancer Institute, is managing the expansion of the Chemical Biology Consortium to 22 sites around the country with world-class expertise in high-throughput screening, structural biology, medicinal chemistry, compound profiling, cancer cell biology, and animal models for oncology. AMRI is participating in the consortium via a research subcontract from Leidos Biomedical Research, Inc., prime contractor for the national lab.

The Chemical Biology Consortium is the discovery engine for the NCI Experimental Therapeutics (NExT) Program focused on advancing new cancer therapeutics against novel molecular and genetic cancer targets. AMRI’s Buffalo facility, which is one of the only U.S.-based fully integrated drug discovery centers with expertise with biology, chemistry and pharmacology, will provide a variety of drug discovery services to the consortium for a period of five years.

"Being selected as a dedicated center for the NExT program is a reflection of AMRI’s commitment and strength as a partner for oncology drug development," said Christopher Conway, senior vice president of Discovery and Development Services at AMRI. "Our integrated drug discovery facility in Buffalo combines multiple scientific disciplines, state of the art technologies, and the capabilities to advance from compound discovery through pharmaceutical product manufacturing – all under one roof. This accelerates drug development by promoting cross-disciplinary collaboration, enabling faster transfer of data and providing partners with greater access via single points of contact. This is especially valuable in oncology drug development, where there is a tremendous emphasis for drug researchers to pursue new and more complex avenues of cancer drug development."

AMRI has more than two decades of experience in successfully identifying, developing and advancing lead compounds through the drug development process. AMRI’s integrated drug discovery center in Buffalo comprises biologists, medicinal chemists and pharmacologists with specific experience in the area of oncology, antibacterials and neurodegenerative disorders. Through collaborative partnerships, AMRI’s integrated drug discovery center provides a variety of technologies that include proprietary informatics to enable increased data analysis for accelerated process development. AMRI’s drug discovery expertise is guided by capabilities that include protein production and purification, high throughput screening, cancer cell biology, chemistry and compound profiling, as well as scale-up synthesis and formulation to support in vivo studies.

About The NCI Experimental Therapeutics (NExT) Program
The mission of the NExT Program is to advance clinical practice and bring improved therapies to patients with cancer by supporting the most promising new drug discovery and development projects. The NCI partners with companies to facilitate the milestone-driven progression of new anticancer drugs (small molecules, biologics) and imaging agents towards clinical evaluation and registration.

On June 14, 2016 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) reported positive response rate results in AML patients with FLT3 (FMS-like tyrosine kinase-3) mutation were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 21st Annual Congress (Press release, Celator Pharmaceuticals, JUN 14, 2016, View Source [SID:1234513295]). The results are from the Company’s Phase 3 trial of VYXEOS (cytarabine: daunorubicin) Liposome for Injection (also known as CPX-351) in patients with high-risk (secondary) acute myeloid leukemia (AML).

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Data, independently validated, from AML patients with a FLT3 mutation demonstrated VYXEOS had a statistically significant improvement in induction response rate (CR+CRi of 68.2% versus 25.0%; p=0.007). A benefit in induction response rate was seen in both FLT3-ITD and FLT3-TKD patients.


Response Rate (responders/number of patients)

VYXEOS (CPX-351)
7+3
FLT3 mutated
15/22 (68.2%)
5/20 (25.0%)
FLT3-ITD
12/19
3/13
FLT3-TKD
3/3
2/7
An improvement in overall survival was also observed in FLT3 mutated patients with median overall survival of 10.25 months in the VYXEOS arm compared to 4.55 months in the 7+3 arm. The Hazard Ratio (HR) was 0.57 (p-value=0.093). In addition, preliminary data on NPM1 and CEBPα mutations were presented showing an improvement in response rate and overall survival in patients with these mutations. Final data for NPM1 and CEBPα mutations is expected to be presented at an upcoming medical conference.

"The improved response and survival observed in this exploratory analysis for VYXEOS over 7+3 in molecularly-defined AML subsets from the Phase 3 trial are promising, particularly for mutated FLT3 patients who typically have a poor prognosis," said Bruno C. Medeiros, M.D., Associate Professor of Medicine, Stanford University Medical Center. "These clinical data corroborate previous ex vivo results suggesting increased sensitivity of FLT3 mutated AML blasts to VYXEOS and supports ongoing and prospective clinical studies in a broader range of AML cohorts."

Approximately 20-30% of AML patients harbor some form of FLT3 mutation. The significance of the mutation, in any given patient, varies according to the nature of the mutation and the context in which it occurs. The most common type of mutation is an internal tandem duplication (ITD) mutation localized to a membrane region of the receptor, while point mutations in the tyrosine kinase domain (TKD) are less common. AML patients with a FLT3 mutation are believed to have a poorer prognosis than the overall population diagnosed with AML.

"We continue to learn more from the Phase 3 trial about the benefit of VYXEOS in AML patients," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. "The results seen in patients with the FLT3 mutation are encouraging and generated the hypothesis that FLT3 mutated AML may be more sensitive to VYXEOS treatment and lead to improved clinical benefit. Further clinical trials are warranted in this patient population."

The company expects to submit a New Drug Application (NDA) for VYXEOS with the U.S. Food and Drug Administration (FDA) by the end of the third quarter of 2016 and submit a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in the first quarter of 2017.

The clinical trial was conducted in partnership with The Leukemia & Lymphoma Society (LLS) through its Therapy Acceleration Program (TAP), which has supported the clinical development of VYXEOS beginning in Phase 2.

Phase 3 Trial Design

The randomized, controlled, Phase 3 trial (Protocol NCT01696084), enrolled 309 patients at 39 sites in the United States and Canada, and compared VYXEOS to the conventional cytarabine and daunorubicin treatment regimen (commonly referred to as 7+3) as first-line therapy in older (60-75 years of age) patients with high-risk (secondary) AML. Patients were stratified for age (60 to 69 and 70 to 75 years of age) and AML type; treatment-related AML, AML with documented history of myelodysplastic syndrome (MDS) with prior treatment with hypomethylating agent therapy, AML with documented history of MDS without prior hypomethlyating agent therapy, AML with a documented history of chronic myelomonocytic leukemia (CMMoL), and de novo AML with a karyotype characteristic of MDS.

Patients were randomized 1:1 to receive either VYXEOS or 7+3. Patients could receive one or two inductions, and responding patients could receive one or two consolidations. First induction for VYXEOS was 100u/m2; days 1, 3, and 5 by 90-minute infusion and for the control arm was cytarabine 100mg/m2/day by continuous infusion for 7 days and daunorubicin 60mg/m2 on days 1, 2, and 3 (7+3). Second induction for VYXEOS-treated patients was 100u/m2 on days 1 and 3, and the control arm was cytarabine 100mg/m2/day by continuous infusion for 5 days and daunorubicin 60mg/m2 on days 1 and 2 (5+2).

Only patients with documented CR or CRi were eligible to receive chemotherapy consolidation. Consolidation for VYXEOS-treated patients was 65u/m2 on days 1 and 3 and the control arm was cytarabine 100mg/m2/day by continuous infusion for 5 days and daunorubicin 60mg/m2 on days 1 and 2 (5+2).

About VYXEOS

VYXEOS (cytarabine:daunorubicin) Liposome for Injection, also known as CPX-351, is a nano-scale co-formulation of cytarabine and daunorubicin at a synergistic 5:1 molar ration. VYXEOS represents a novel approach to developing combinations of drugs in which molar ratios of two drugs with synergistic anti-tumor activity are encapsulated in a nano-scale liposome in order to maintain the desired ratio following administration. The FDA granted Breakthrough Therapy designation to VYXEOS for the treatment of adults with therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC). VYXEOS was granted orphan drug status for the treatment of AML by the FDA and the European Commission. VYXEOS was also granted Fast Track designation for the treatment of elderly patients with secondary AML by the FDA.

About AML

Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood characterized by the uncontrolled proliferation of immature blast cells in the bone marrow. AML is generally a disease of older adults, and the median age of a patient diagnosed with AML is about 67 years. The American Cancer Society estimates that there will be 19,950 new cases of AML and 10,430 deaths from AML in the U.S. in 2016. In Europe the number of new cases is estimated to be 18,000 and in Japan the number is 5,500. The Company estimates that nearly 70 percent of AML patients are over the age of 60, and approximately 75% are intermediate or high risk. Furthermore, approximately half of those patients are considered suitable for intensive treatment.

Even with current treatment, overall survival for AML is poor. In patients over 60 years of age, the 5 year survival rate is less than 10%. In high-risk (secondary) AML, overall survival is lower, resulting in an acute need for new treatment options for these patients.

On June 14, 2016 Cascadian Therapeutics (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported that it will present clinical data from the Company’s ongoing Phase 1b studies, including updated clinical data from the study of ONT-380 in combination with trastuzumab and capecitabine ("Triplet"), and a review of the recent ASCO (Free ASCO Whitepaper) data from the ONT-380 combination with T-DM1, at today’s Corporate Update and R&D Day in New York City (Press release, Cascadian Therapeutics, JUN 14, 2016, View Source [SID:1234513293]). ONT-380 is an oral, highly selective small molecule HER2 inhibitor being studied as a combination therapy to treat HER2+ locally advanced or metastatic breast cancer, including patients with brain metastases.

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"The data suggest that ONT-380, in combination with other active agents, show systemic activity in pretreated patients, supporting its advancement into later stage studies," said Erika Hamilton, MD, Director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute. "To date, ONT-380 has shown a favorable tolerability profile and the potential to improve outcomes in patients with brain metastases. Historically, great progress has been made with the approval of HER2 targeted therapies, however, patients with metastatic disease will eventually progress and need additional therapies. A new agent that can impact both systemic and brain metastases, while not adding significant toxicities, may be a substantial benefit for patients."

ONT-380 "Triplet" Phase 1b Data Update
The ongoing Phase 1b "Triplet" study is evaluating a combination of ONT-380 with trastuzumab and capecitabine in 27 previously treated, locally advanced or metastatic breast cancer patients with and without brain metastases. Patients had received a median of three prior HER2 directed agents: 100% with trastuzumab and T-DM1, and 74% with pertuzumab. Additionally, 41% of patients entered the trial with brain metastases.

Results from the combination trial show:

Safety Profile

Majority of adverse events were Grade 1, with most patients being able to continue on the full dose of ONT-380
Grade 3 diarrhea was infrequent, seen in 3/27 patients (11%) without a requirement for prophylactic anti-diarrheal medicine
Activity

Overall objective response rate (ORR), as defined by RECIST 1.1, of 58% (24 patients with measurable disease at baseline: 1 complete response, 13 partial responses, 6 with stable disease, 4 with progressive disease)
Interim median progression-free survival (mPFS) of 6.3 months overall (95% CI 4.1- n/a)
Patients with brain metastases

Outcomes in patients with brain metastases were similar to patients without brain metastases
"Our median PFS of 6.3 months and 58% objective response rate are promising in patients previously treated with T-DM1," commented Luke Walker, MD, Vice President of Clinical Development of Cascadian Therapeutics. "There are no true historical data with a comparable patient population given the recent changes in HER2 treatment. However, we believe a reasonable comparator is the Phase 3 TH3RESA trial of advanced HER2+ breast cancer, where patients in the control arm had a 3.3 month median PFS and 9% objective response rate. These patients received two prior HER2 agents and were treated on study with chemotherapy and/or an anti-HER2 agent, similar to current treatment options following T-DM1. Investigators continue to remain enthusiastic about advancing our Triplet combination into later stage studies."

Next steps
An ongoing Phase 2 study, known as HER2CLIMB, is exploring the Triplet combination in a randomized, double blind, placebo-controlled setting. This trial is enrolling patients with locally advanced or metastatic HER2+ breast cancer with prior treatment with a taxane, trastuzumab, pertuzumab, and T-DM1, including patients with brain metastases. This trial is expected to enroll 180 patients across approximately 100 clinical sites in the United States, Canada, and Western Europe. The HER2CLIMB trial is designed to show a 50% improvement in median PFS, with an assumption of 4.5 months in the control arm.

Commented Scott Myers, President and CEO of Cascadian Therapeutics, "We are pleased to report these encouraging clinical data and look forward to discussing the results with investigators and regulators to determine how best to advance the ONT-380 program. We anticipate providing updated data by year-end."