4:54 PM
 | 
Apr 26, 2018
 |  BC Innovations  |  Targets & Mechanisms

Raising metabolism

Why immuno-metabolism is the next white space area of cancer immunotherapy

In the wake of the failure of ECHO-301, drug developers are asking whether the trial design or the target is at fault. But while the value of IDO1 as a target is still in doubt, the result has done little to dampen enthusiasm among immuno-oncologists for the idea of interrupting metabolic pathways to treat cancer.

Cancer metabolism has long been a focus in oncology, but innovators have recently turned to new ways of blocking metabolic processes related to immunosuppression in the tumor microenvironment.

Last month, two newcos emerged with immuno-metabolism-based platforms. Dracen Pharmaceuticals Inc. announced on March 20 a $40 million series A round led by Deerfield Management to develop glutamine antagonists to treat cancer. Two days later, Third Rock Ventures brought Rheos Medicines Inc. out of stealth mode with a $60 million A round, with an immuno-metabolism platform for autoimmune diseases and cancer.

In the last three years, at least seven companies have been launched with single assets or platforms based on blocking immuno-metabolism in cancer, raising a total of over $515 million in venture and $138 million in public financing (see “Cancer Immuno-metabolism Newcos”).

Table: Cancer immuno-metabolism newcos

Since the start of 2015, at least seven new companies have been formed with therapeutic programs for cancer immuno-metabolism targets or with platforms to identify new targets and compounds. The targets fall into four main metabolic pathways: the adenosine, glutamine, indoleamine 2,3-dioxygenase (IDO; INDO) and prostaglandin E2 (PGE2) pathways. All disclosed funding is from venture rounds with the exception of Arcus Biosciences Inc. (NYSE:RCUS), which raised $138 million in an IPO in March. Source: BCIQ: BioCentury Online Intelligence, company websites

CompanyPathwayTargetStatusRaised ($M)Founded
Arcus Biosciences Inc. (NYSE:RCUS)Adenosine Adenosine A2A receptor (ADORA2A); ADORA2BPh I$364.72015
Ecto-5'-nucleotidase (CD73; NT5E)Preclin
Ideaya Biosciences Inc.IDO Aryl hydrocarbon receptor (AHR)Preclin$140 2015
Rheos Medicines Inc.UndisclosedUndisclosedPreclin$60 2016
Dracen Pharmaceuticals Inc.Glutamine UndisclosedPreclin$40 2016
Kyn Therapeutics Inc.PGE2 Prostaglandin E2 receptor EP4 subtype (PTGER4)Ph I$28 2016
IDO AHRPreclin
KynureninePreclin
Arrys Therapeutics Inc.PGE2 PTGER4Ph I$21 2017
Elpiscience Biopharmaceuticals Co. Ltd.Adenosine CD39PreclinND2017

In all, at least 39 companies have active cancer programs against immuno-metabolism targets, according to BioCentury’s BCIQ database (see “Companies by Metabolic Pathway”).

Incyte Corp.’s IDO1 inhibitor epacadostat was one of the most advanced compounds to sit at the intersection of cancer metabolism and immuno-oncology.

On April 6, Incyte announced that the Phase III combination trial ECHO-301 of epacadostat with partner Merck & Co. Inc.’s Keytruda pembrolizumab missed the primary endpoint of improving progression-free survival (PFS) vs Keytruda alone in first-line metastatic melanoma. Epacadostat had also failed as a single agent in a Phase I trial in 52 patients with advanced solid tumors.

While success would have validated the target, its failure has had little impact on companies pursuing immuno-metabolism.

Companies that spoke with BioCentury said the momentum in the...

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