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Investigational PD-1 Immune Checkpoint Inhibitor Nivolumab Receives U.S. FDA Breakthrough Therapy Designation for Hodgkin Lymphoma

On May 14, 2014 Bristol-Myers Squibb reported that the U.S. Food and Drug Administration (FDA) has granted the investigational PD-1 immune checkpoint inhibitor nivolumab Breakthrough Therapy Designation for the treatment of patients with Hodgkin lymphoma (HL) after failure of autologous stem cell transplant and brentuximab (Press release Bristol-Myers Squibb, MAY 14, 2014, View Source [SID:1234500524]). The designation is based on data from a cohort of patients with HL in the company’s ongoing Phase 1b study of relapsed and refractory hematological malignancies.

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Investigational PD-1 Immune Checkpoint Inhibitor Nivolumab Showed Antitumor Activity in Previously Treated and Chemotherapy-Naïve Patients in Phase 1b Non-Small Cell Lung Cancer Trials

On May 14, 2014 Bristol-Myers Squibb reported from a Phase1b study evaluating the safety and efficacy of its investigational PD-1 immune checkpoint inhibitor nivolumab as a single agent in patients with advanced non-small cell lung cancer (NSCLC) who were previously treated (Study -003) and a Phase 1b study evaluating nivolumab as a single agent in chemotherapy-naïve patients (CheckMate -012) (Press release Bristol-Myers Squibb, MAY 14, 2014, View Source [SID:1234500525]). In Study -003, the two-year survival rate was 24% across doses (n=129) for previously-treated patients who received nivolumab as a single agent and highest at 45% in patients who received the 3 mg/kg dose (n=37). In CheckMate -012, the overall response rate (ORR) was 50% in PD-L1 positive tumors and 0% in PD-L1 negative tumors for chemotherapy-naïve patients who received nivolumab as a single agent (n=20). The types of treatment-related serious adverse events (SAEs) in CheckMate -012 were consistent with those in other nivolumab trials with 15% of patients experiencing grade 3-4 treatment-related SAEs. These data will be presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) taking place in Chicago May 30-June 3.

Results from Phase 1b Single Agent Study in Previously-Treated Patients (Study -003)

Study -003 is a Phase 1b dose escalation study (n=306) evaluating the safety, antitumor activity and pharmacokinetics of nivolumab as a single agent in previously-treated patients with advanced melanoma (n=107), NSCLC (n=129), renal cell carcinoma (n=34), castration-resistant prostate cancer (n=17) or colorectal cancer (n=19). Based on an amendment to the protocol, patients were followed for survival. Eligible patients were administered nivolumab as an intravenous infusion every two weeks of each eight-week treatment cycle. Cohorts of three to six patients per dose level (0.1, 0.3, 1.0, 3.0 or 10 mg/kg) were enrolled sequentially. Patients continued treatment ≤2 years (12 cycles), unless they experienced complete response, unacceptable toxicity, progressive disease or withdrew consent.

Efficacy and safety results from this study were initially presented at ASCO (Free ASCO Whitepaper) and published in the New England Journal of Medicine in 2012. Updated results from the lung cancer cohort, including those shown below, will be presented at ASCO (Free ASCO Whitepaper) on May 31 at 1:15 p.m. CDT (Abstract #8112).

Data to be presented at the 2014 ASCO (Free ASCO Whitepaper) annual meeting, with all patients having greater than or equal to one year of follow up, demonstrated a spectrum, frequency and severity of treatment-related adverse events (AEs) that were consistent with those initially reported in the study at ASCO (Free ASCO Whitepaper) in 2012. Common drug-related AEs included fatigue, decreased appetite, diarrhea, nausea, constipation, cough and dyspnea. Drug-related select AEs with potential immunologic etiologies, defined as adverse events that may require more frequent monitoring and/or unique intervention, included rash, diarrhea and pruritus. These data support the ongoing evaluation of nivolumab as a single agent at the 3 mg/kg dose in patients with previously treated advanced NSCLC in the Phase 3 CheckMate -017 and CheckMate -057 studies.

Results from Phase 1b Study of Chemotherapy-Naïve Patients (CheckMate -012)

CheckMate -012 is a multi-arm Phase 1b trial evaluating the safety and tolerability of nivolumab in patients with chemotherapy-naïve advanced NSCLC, as either a single agent or as part of a regimen with other agents, including in combination with Yervoy (ipilimumab), at different doses and schedules. Secondary outcomes include ORR and progression free survival (PFS). Results from patients who received nivolumab as a single agent, including those shown below, will be presented at ASCO (Free ASCO Whitepaper) on June 3 at 11:30 a.m. CDT (Abstract #8024).

In patients who received nivolumab 3 mg/kg as a single agent (n=20), the objective response rate (ORR) was 50% in patients whose tumors were PD-L1 positive and 0% for tumors that were PD-L1 negative. Responses were observed in both squamous and non-squamous histological subtypes. Median duration of response has not been reach after a median of 15 months of follow up.

After a median of 15 months of follow up, grade 3/4 treatment-related SAEs were reported in 3 patients (15%) and included AST (5%) or ALT (5%) elevations, cardiac failure and hyperglycemia (5%). No pneumonitis (any grade) was observed. These data support the ongoing evaluation of nivolumab as a single agent at the 3 mg/kg dose in the first-line treatment of advanced NSCLC patients in the Phase 3 CheckMate -026 study.

Data from additional arms of CheckMate -012, including nivolumab as part of a regimen with chemotherapy doublets and erlotinib, is also to be presented at ASCO (Free ASCO Whitepaper) 2014 (Abstract #8113, #8022).

ASLAN Pharmaceuticals signs agreement with CSL to develop novel therapy for asthma

On May 13, 2014 ASLAN Pharmaceuticals Pte Ltd reported a global license agreement to develop CSL Limited’s (ASX:CSL) anti-IL13 receptor monoclonal antibody, CSL334, currently in preclinical development for the treatment of asthma (Press release, ASLAN Pharmaceuticals, MAY 13, 2014, View Source [SID:1234512883]).
Under the agreement, ASLAN will fund and develop CSL334 through to clinical proof of concept in a development program conducted primarily in Asia, targeting patients suffering moderate persistent to severe allergic asthma whose disease is not adequately controlled by existing treatments. Upon achievement of clinical proof of concept, ASLAN will identify a global partner for phase 3 development and commercialisation.

"Many patients with moderate and severe asthma still do not have their disease adequately controlled by current therapies, and these patients represent around half of the total burden of asthma worldwide," said Dr Mark McHale, ASLAN’s Chief Operating Officer. "Some major companies are now pursuing strategies to help these patients, many of whom live in fear of their next serious exacerbation. As one of the leaders in the biologics industry, CSL have developed a unique approach to controlling the pathways responsible for this disease."

"The IL-13 receptor signalling pathway plays a critical role in allergic airway disease, and CSL has had an interest in inhibiting this target since it was first identified at the Walter and Eliza Hall Institute of Medical Research in Australia. This led CSL scientists to discover and optimise the monoclonal antibody inhibitor known as CSL334," commented Andrew Nash, CSL’s Senior Vice President, Research. "ASLAN’s focus on efficiently designing and executing innovative clinical strategies, combined with its teams experience in asthma drug development, make it the ideal partner for moving this therapy forwards."

CSL will be entitled to share returns generated by ASLAN from partnering the project. Further financial details were not disclosed.

About CSL334 inhibitor
CSL334 is a fully human monoclonal antibody against interleukin-13 receptor α1 that has been shown to block binding and signal transduction of both IL4 and IL13. CSL334 is currently in preclinical development.

Servier enters into a global collaboration agreement for the development and the commercialization of new drugs candidates targeting apoptosis in oncology

On May 13, 2014 Servier reported it has signed a strategic worldwide collaboration agreement with Novartis to develop and commercialize a series of novel drug candidates issued from Servier research programs in partnership with Vernalis in oncology, targeting apoptosis regulation pathways (Press release, Servier, MAY 13, 2014, View Source [SID:1234508829]).

The collaboration covers the worldwide codevelopment of BCL-2 selective inhibitor candidates now entering into clinical development. Proteins of the BCL-2 family are crucial regulators of apoptosis. Dysregulation of this protein family play a major role in the aberrant survival of tumor cells.

Servier will remain responsible for research activities and will share responsibilities with Novartis to conduct a clinical development program aimed at moving swiftly toward a first indication for the benefit of patients.

Commercialization rights for products arising from the collaboration will be allocated between the parties on a geographic basis.

Jean-Pierre Abastado, Ph D, Director of the Center of Therapeutic Innovation in Oncology at Servier, said: "Small molecules tailored against specific targets can have very high therapeutic potential. This success was achieved through a comprehensive chemistry and biology research program, in collaboration with Vernalis, with our teams identifying and characterizing this exquisitely specific BCL-2 inhibitor. These new compounds further extend Servier’s portfolio beyond kinase inhibitors, HDAC inhibitors; and immunotherapeutic products."

Emmanuel Canet, MD, PhD, President of Servier R&D, commented that "this significant partnership is the recognition of Servier’s innovative approach to oncology research. By collaborating with one of the leaders in the field we are restating our commitment to provide innovative therapeutic solutions for unmet needs in patients with severe illnesses."

About the BCL-2 target:

Proteins of the BCL-2 family are crucial regulators of apoptosis, the programmed cell death. Dysregulations of this protein family play a major role in the aberrant survival of tumor cells. Within this protein family, BCL-2 belongs to the prosurvival members and is often overexpressed in tumor cells. Prosurvival BCL-2 family members have been recognized as attractive therapeutic targets in oncology for more than twenty years; but drug discovery research on this type of target is particularly challenging and requires innovative chemistry supported by structural biology.

Valneva Reports Q1 2014 Results, Confirms Full Year Outlook, and Provides Business update

Valneva´s partners Novartis and GlaxoSmithKline (GSK) to join forces and exchange assets
Novartis and GlaxoSmithKline (GSK) announced a major contemplated transaction, including the divestment of Novartis’ vaccine business (excluding flu) to GSK, expected to close in the first half of 2015 (Press release, Valneva, MAY 13, 2014, View Source;file=2014_05_13_Valneva_Q1_PR_EN.pdf [SID:1234502168]).
Overall, Valneva expects to benefit from its two existing strategic partners joining forces. The Company sees Valneva’s key assets partnered with Novartis as potentially highly complementary to GSK.
Valneva’s late stage Pseudomonas and C. difficile vaccines are not programs GSK already has in its R&D portfolio and may add significant value to the GSK R&D portfolio.
The Company does not expect any impact regarding its Flu/EB66 cell-culture partnership with GSK since the Novartis flu business (including their cell-culture based flu vaccine) is not part of the contemplated transaction at this point in time.