It’s another fail for AstraZeneca’s I-O combo, but it may not mean what you think

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.

New Oncology Clinical Collaboration between Nektar and Takeda to Evaluate Combination of NKTR-214, a CD122-biased Agonist, and TAK-659, a Dual SYK and FLT-3 Inhibitor, in Liquid and Solid Tumors

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

Exicure Announces Chief Executive Officer, Dr. David Giljohann, Named to Endpoints News’ “Under-40s” Biopharma Executives List

On April 24, 2018 Exicure, Inc., the pioneer in gene regulatory and immunotherapeutic drugs utilizing three-dimensional, spherical nucleic acid (SNA) constructs, reported that the Company’s Chief Executive Officer, David Giljohann, Ph.D., has been recognized by Endpoints News as an outstanding up-and-coming biopharma professional under the age of 40 (Press release, Exicure, APR 24, 2018, View Source;p=RssLanding&cat=news&id=2344263 [SID1234525632]).

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Dr. Giljohann was Exicure’s founding scientist in 2011. He has served as Chief Executive Officer since November 2013 and on the Company’s Board of Directors since March 2014. He completed his Ph.D. in the laboratory of Dr. Chad A. Mirkin where he developed oligonucleotide-modified nanoparticles, including Exicure’s Spherical Nucleic Acid (SNA) constructs.

"It is an incredible honor to be recognized in Endpoints News’ under-40s biopharma professionals list," states Dr. Giljohann, 37. "I would like to see a dramatic change in how quickly we can design and develop drugs for patients in need, and this is a driving force for our team at Exicure. With three drugs now in the clinic, we hope that the advancement of our SNA technology can provide great promise for a broad range of chronic conditions and orphan diseases."

Dr. Giljohann has been recognized for his work with a Materials Research Society Gold Award, Baxter Innovation Award, Rappaport Award for Research Excellence, NSEC Outstanding Research Award, and as a finalist in the National Inventors Hall of Fame Collegiate Inventors Competition. Dr. Giljohann has contributed to over 25 manuscripts and over 100 patents and applications. He received his Ph.D. in 2009 from Northwestern University.

PATENT TRIAL AND APPEAL BOARD DENIES HOLOGIC CHALLENGE

TO ENZO BIOCHEM PATENT INVOLVED IN DELAWARE INFRINGEMENT CASE

On April 24, 2018 Enzo Biochem, Inc. (NYSE: ENZ) and its subsidiary Enzo Life Sciences, Inc. reported that the Patent Trial and Appeal Board has denied a petition filed by Hologic, Inc. (Nasdaq: HOLX) for inter partes review, a procedure for challenging the validity of patent claims, against U.S. Patent 6,221,581. Enzo Life Sciences, Inc. is asserting U.S. Patent 6,221,581 in patent infringement litigation against Hologic, Inc., Grifols Diagnostic Solutions, Inc., and Grifols S.A. in the U.S. District Court for the District of Delaware (Press release, Enzo Biochem, APR 24, 2018, View Source [SID1234525631]).

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Coherus BioSciences to Report First Quarter 2018 Financial Results on May 10th  

On April 24, 2018 Coherus BioSciences, Inc. (Nasdaq:CHRS), reported that its first quarter 2018 financial results will be released after market close on Thursday, May 10, 2018 (Press release, Coherus Biosciences, APR 24, 2018, View Source/phoenix.zhtml?c=253655&" target="_blank" title="View Source/phoenix.zhtml?c=253655&" rel="nofollow">View Source;p=RssLanding&cat=news&id=2344193 [SID1234525630]). Starting at 4:30 p.m. EDT, Coherus’ management will host a conference call to discuss the financial results and provide a general business update.

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After releasing first quarter 2018 financial results, we will post them on the Coherus BioSciences website at View Source." target="_blank" title="View Source." rel="nofollow">View Source

Conference Call Information
When: Thursday, May 10, 2018 at 4:30 p.m. ET
Dial-in: (844) 452-6826 (toll free) or (765) 507-2587 (International)
Conference ID: 2767588
Webcast: View Source
Please join the conference call at least 10 minutes early to register. The webcast will be archived on the Coherus website.