On April 24, 2018 Nektar Therapeutics (NASDAQ:NKTR) reported that it has entered into a new clinical collaboration with Takeda Pharmaceutical Company Limited to evaluate Nektar’s investigational medicine, NKTR-214, with Takeda’s investigational medicine, TAK-659, as a potential combination treatment regimen in multiple cancer settings (Press release, Nektar Therapeutics, 24 24, 2018, View Source [SID1234525633]). NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. TAK-659 is a dual inhibitor of both spleen tyrosine kinase (SYK), a kinase involved in cell proliferation and FLT-3, a cytokine receptor in the receptor tyrosine kinase class III.

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"We look forward to collaborating with Takeda to explore a range of combination therapy approaches with NKTR-214 and TAK-659 in liquid and solid tumor settings," said Jonathan Zalevsky, PhD, Chief Scientific Officer and Senior Vice President of Research, Nektar. "Importantly, this clinical collaboration will allow us to understand how we can increase the clinical benefit of immunotherapies for patients when we leverage multiple I-O modalities and target the immune cycle in complementary and novel ways."

Under the terms of the collaboration, Nektar and Takeda will each maintain global commercial rights to their respective investigational medicines. Nektar and Takeda will split the costs related to the clinical trial and each company will contribute their respective compounds to the clinical collaboration. The first trial is expected to start in the second half of 2018 and will evaluate the combination of an every three-week schedule of NKTR-214 with oral daily doses of TAK-659 in patients with Non-Hodgkin Lymphoma.

"Based upon highly compelling preclinical data, we are looking forward to combining Nektar’s unique CD122-biased agonist with TAK-659, which is a dual inhibitor of both SYK and FLT-3," said Phil Rowlands, PhD, Head, Oncology Therapeutic Area Unit, Takeda. "NKTR-214 is unique in that it can stimulate tumor-killing T-cells in the tumor micro-environment itself. By combining with TAK-659, we hope to target different stages of the cancer immunity cycle in a combination regimen. This collaboration is aimed at achieving our goal of allowing more patients with different types of cancer to benefit from immunotherapies."

NKTR-214 is an investigational immuno-stimulatory therapy designed to expand specific cancer-fighting CD8+ effector T cells and natural killer (NK) cells directly in the tumor micro-environment and increase expression of PD-1 on these immune cells. NKTR-214 targets CD122 specific receptors found on the surface of these cancer-fighting immune cells in order to stimulate their proliferation. NKTR-214 is being evaluated in multiple clinical trials in cancer patients. It has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

TAK-659 is an orally-available investigational reversible dual SYK/FLT-3 inhibitor. SYK is a non-receptor cytoplasmic kinase that binds to phosphorylated immuno-receptor tyrosine-based activating motifs and mediates cellular proliferation and survival. Mutations in FLT-3 genes can result in the constitutive activation of the FLT-3 receptor and result in acute myeloid leukemia and acute lymphoblastic leukemia. TAK-659 demonstrates both direct- and immune-mediated tumor cell kill mechanisms. It is currently being explored in clinical studies as a single agent and in combination in solid and hematological malignancies

On April 24, 2018 In conjunction with DURECT Corporation’s(Nasdaq: DRRX) reported that its first quarter 2018 financial results press release, you are invited to listen to a conference call that will be broadcast live over the internet on Wednesday, May 2, 2018 at 4:30 pm Eastern Time (1:30 pm Pacific Time) (Press release, DURECT, APR 24, 2018, http://investors.durect.com/phoenix.zhtml?c=121590&p=irol-newsArticle&ID=2344347 [SID1234525651]).

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A live audio webcast of the presentation will be available by accessing DURECT’s homepage at www.durect.com and clicking "Investor Relations." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under Audio Archive in the "Investor Relations" section.

The filing is based on data from the Phase III KEYNOTE-189 trial, which showed that first-line use of Keytruda (pembrolizumab) in combination with pemetrexed (Lilly’s Alimta) and cisplatin or carboplatin slashed the risk of death by 51 percent compared with chemotherapy alone (Press release, PharmaTimes, APR 24, 2018, View Source [SID1234525615]).

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An overall survival benefit was observed regardless of PD-L1 expression, the firm noted.

"We are very pleased that the centralized review process is underway, and are hopeful that this new combination regimen will soon become available for appropriate patients in Europe who have been diagnosed with metastatic lung cancer," noted Dr Roger Perlmutter, president, Merck Research Laboratories.

If approved by the European Medicines Agency, this would mark the third indication for Keytruda in metastatic NSCLC to be approved in Europe based on overall survival data.

MSD initially pulled back its European application to market the combo in October last year, with media reports at the time suggesting that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) was reluctant to back approval.

That filing was based on a cohort of the KEYNOTE-021 trial, which MSD insisted "demonstrated significant improvements in overall response rate (ORR) and progression-free survival (PFS) for the Keytruda combination regimen compared to chemotherapy alone".

Analysts at Goldman Sachs reportedly said this week that Keytruda could be a $16-billion asset by 2025, pushing MSD’s stock to a three-month high, according to Investor’s Business Daily.

AstraZeneca has come up short in another lung cancer trial of its immuno-oncology combo, this time in patients who’ve failed on two prior treatments (Press release, AstraZeneca, APR 24, 2018, View Source;utm_medium=rss [SID1234525635]).

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But investors shouldn’t use the outcome to predict the forthcoming results of a closely watched first-line study, analysts say.

Tuesday, the British drugmaker said its PD-L1 med Imfinzi and candidate tremelimumab had failed to improve survival in third-line patients whose tumors didn’t express PD-L1. There was a bright spot, though: A substudy that pitted solo Imfinzi against chemo in PD-L1-positive patients showed a "clinically meaningful" difference for the AZ drug in the risk of death.

The results weren’t terribly surprising to analysts; Bernstein’s Tim Anderson, for one, said in a note to clients that he thought the trial, dubbed Arctic, "was likely to yield mixed results (and it did)."

And the way he sees it, that’s not such a bad thing. Overall, "the field has moved on," he said, calling Arctic "basically the hangover from a now abandoned hypothesis" that PD-L1/CTLA4 pairings such as AZ’s will extend benefits to the PD-L1 negative population.

ODDO BHF’s Pierre Corby wrote in his own note to clients that removing the combination from models would have "minimum impact."

RELATED: AstraZeneca’s Mystic shortfall is an immuno-oncology shake-up for Bristol-Myers and a bolster for Merck and Roche

And while investors may be tempted to take the outcome as a sign that the Imfinzi-tremelimumab combo is destined for failure in first-line, PD-L1-positive patients—the all-important population in the I-O market—they shouldn’t, Anderson said.

"That outcome is certainly not foreshadowed" by the miss in PD-L1 negative patients, he wrote.

If there’s any readthrough to Mystic, AstraZeneca’s first-line trial, it’s that Imfinzi still holds promise as a monotherapy, Anderson figures.

"We continue to believe that Imfinzi is likely is show an OS benefit in 1L PD-L1(+) patients, and obtain a (modest) foothold in the market," he wrote.

RELATED: 2018 is here. Now get ready for ‘market-defining’ I-O readouts

Of course, it’ll still be a while before industry watchers have that data, which is slated to arrive in the second half of the year. And in the meantime, there will be plenty of other key I-O news from companies including Merck and Roche that should keep investors busy.

On April 24, 2018 REVOLUTION Medicines, Inc., a drug discovery and development company focused on frontier cancer targets, reported it has raised $56 million in a Series B financing to support its ongoing R&D programs and general business activities (Press release, Revolution Medicines, APR 24, 2018, View Source [SID1234525652]). The financing was supported by a syndicate of premier life sciences investors led by Nextech Invest, an oncology-focused investment firm, and included participation from Casdin Capital, Schroder Adveq, The Column Group, Third Rock Ventures and additional undisclosed institutional investors.

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In addition, the company announced the expansion of its leadership team with the appointment of Ryan Martins as chief financial officer; Xiaolin Wang, D.Sc., as senior vice president, clinical development; and Hirdesh Uppal, D.V.M., Ph.D., as vice president, development sciences. Thilo Schroeder, Ph.D., partner at Nextech Invest, and Barbara Weber, M.D., chief executive officer of Tango Therapeutics, joined the company’s board of directors.

"We appreciate the strong support shown by our founding and new investors in this significant financing that will fuel the advancement of our exciting SHP2 program and innovative pipeline," said Mark A. Goldsmith, M.D., Ph.D., president and chief executive officer at REVOLUTION Medicines. "The raise of new capital, expansion of our executive team and board with seasoned leaders, and multiple presentations about progress in our SHP2 program at the recent AACR (Free AACR Whitepaper) conference all reflect enormous momentum in our effort to outsmart cancer."

Leadership Team and Board of Directors Appointments

Mr. Martins joins REVOLUTION Medicines from Ultragenyx, where he served as vice president, finance, corporate strategy and investor relations with responsibility for capital raising, investor relations, financial and competitive analysis, strategic planning and business development. Mr. Martins was previously a biotechnology analyst at investment banks including Lehman Brothers, Barclays, Lazard and Jefferies.
Dr. Wang joins the company from Acerta Pharma, where she held a senior leadership position in clinical development and was instrumental in the recent approval of acalabrutinib (Calquence). Dr. Wang previously served in leadership positions in clinical development and biometrics at Genentech and Geron.
Dr. Uppal joins REVOLUTION Medicines from Medivation, where he led translational medicine and diagnostics until the company’s acquisition by Pfizer. Prior to Medivation, Dr. Uppal served in development roles at Roche and Genentech.
Dr. Schroeder is a partner at Nextech Invest. He has served as director or observer on the boards of Blueprint Medicines, IDEAYA Bioscience, and Peloton Therapeutics, and previously conducted research on designed ankyrin repeat proteins (DARPins) as specific protein inhibitors at the University of Zurich.
Dr. Weber is chief executive officer of Tango Therapeutics. Prior to Tango, she led oncology translational medicine at Novartis, oncology discovery and translational medicine at GlaxoSmithKline, the University of Pennsylvania Cancer Center Breast Cancer Program and cancer genomics at the Abramson Cancer Research Institute.
"I am very enthusiastic about the high-quality cancer drug discovery and development work being done by REVOLUTION Medicines and am pleased to support this world-class team to help advance the company’s mission on behalf of patients in need," said Dr. Schroeder.

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