Skip to main content
Premium Trial:

Request an Annual Quote

Entelos Extends RA Deal with Organon to Gain First Therapeutic Ownership Rights


Entelos last week announced that it had expanded an existing agreement with Organon in a deal that marks the first time the biosimulation firm will be able to co-promote and commercialize therapeutic products that result from a collaboration.

The agreement extends a partnership that the firms initiated in 2001 to develop a version of Entelos’ PhysioLab simulation platform focused on rheumatoid arthritis. Entelos delivered five novel RA targets to Organon last year that it identified using the RA PhysioLab, a large-scale mathematical model of a rheumatoid arthritis joint. Last week, the companies agreed to expand their relationship beyond discovery, and to co-develop biologic and small-molecule therapeutics directed at those targets.

While financial terms of the deal were not disclosed, Entelos CEO James Karis said that the agreement is “quite significant” for his company. “It’s the first time we’ve had co-promotion, co-development, and ownership rights for a compound,” he said.

Noting that the PhysioLab technology “is applicable across the pipeline,” Karis said that Entelos partnered in the past with drug developers at different stages in the pipeline, “but what’s new here is the fact that we have an agreement now to work from the beginning to the end, so the comprehensiveness of the agreement is new — not the different steps in it.”

Henri Theunissen, manager of research alliances at Organon, told BioInform that the company plans to use its wet lab capabilities to validate the targets that Entelos identified, and will apply the PhysioLab technology to help predict novel RA biomarkers, with longer-term plans calling for use of the technology in clinical studies.

“Of course, it’s very ambitious that we will do all that by using a computer,” Theunissen said, noting that the companies have set up an “intricate collaboration” involving Entelos’ in silico capabilities and Organon’s wet lab work. He said that PhysioLab is also integrated with Organon’s in-house bioinformatics pipeline, as well as its knowledge-management infrastructure.

The agreement marks the second extension of the partnership. In late 2002, Organon agreed to provide up-front fees, milestone payments, and royalties on the sale of immunological and inflammatory drugs resulting from the collaboration. The Netherlands-based company also agreed to fund further development of the RA PhysioLab.

Now, Organon will help support the development of what Entelos calls the “third generation” of the RA PhysioLab. Over the next two years, Entelos said, the platform will be extended to include “additional biological detail, such as B cells and dendritic sells, as well as a serum compartment to conduct biomarker research.”

The company will collaborate with Organon scientists in an iterative fashion to feed new data into the model, run a series of simulations, and suggest specific experimental protocols in order to gather additional biological knowledge that can be added to the model.

Karis acknowledged that the “third-generation” nomenclature is a slightly misleading way to describe the development of the platform, which follows “more of an evolutionary process” than the stepwise release cycle for software products.

“We’re not talking about a software situation here,” he said. “It really is a research environment.” Oddly, as the concept of biosimulation gains ground in the biological research community, Entelos is finding that “it’s hard to get that [concept] across to the public right now. There’s so much out there about systems biology and in silico biology, and there are a lot of different things going on” that make it difficult for Entelos to delineate the “unique capabilities” of its platform.

But the latest agreement with Organon is a sign that the market is willing to apply in silico methods to “truly accelerate the drug-discovery and -development pipeline” with the goal of “getting to a therapeutic faster,” Karis said.

Theunissen ceded that biosimulation “still needs to be proven” as an approach in drug discovery research, but added that the potential benefits of the technology could be worth the risk.

“The added value is difficult to quantify, but our reason for doing this is not only because we like the technology, but that in the end it should show, somehow, in the output of our research,” he said. “That can either be in terms of speed or in terms of quality, so ideally this technology will make the R&D process more speedy, and ideally the targets that have been delivered will be of a higher quality in terms of innovative power and also a higher quality in the sense that their attrition rate is lower than traditionally.”

However, he added, “these are all ideal hopes, and maybe, to some extent, guesses.”

Organon has stepped up as an early adopter in the biosimulation space, Theunissen said, as part of a broader partnership strategy that he characterized as “more outward looking than we have been in past years.”

Organon is “a medium-sized company,” he said, “and by definition, that means that there is a lot more going on outside Organon than inside Organon.” Therefore, he said, the company sees “enormous potential” for externally developed technologies that it considers to be novel, such as PhysioLab.

Karis said that Entelos’ technology has particular potential for RA research because animal models haven’t been effective substitutes for human physiology in rheumatoid arthritis. “It’s a disease that develops over long periods of time, which is a big, big challenge for traditional model systems,” he said. “Here you have a dynamic mathematical model, so you can accelerate time scales and it gives you a whole other dimensional capability. You have this multifactorial disease with a very slow development process, and mathematically, now, you can deal with those issues, and you can’t do that any other way.”

Theunissen, who led Organon’s bioinformatics and genomics research efforts before taking his current position, said that the promise of replacing animal models has always been “the big sunny future for bioinformatics, but it’s not realistic to assume that we’re there yet.” PhysioLab is complementary to animal models, he said, and may prove useful in guiding wet lab experiments, but will not eliminate the need for them in the near future.

The RA PhysioLab is the “first or second step” in that direction, he added, “but it’s certainly not the final step.”

— BT

Filed under

The Scan

Mosquitos Genetically Modified to Prevent Malaria Spread

A gene drive approach could be used to render mosquitos unable to spread malaria, researchers report in Science Advances.

Gut Microbiomes Allow Bears to Grow to Similar Sizes Despite Differing Diets

Researchers in Scientific Reports find that the makeup of brown bears' gut microbiomes allows them to reach similar sizes even when feasting on different foods.

Finding Safe Harbor in the Human Genome

In Genome Biology, researchers present a new approach to identify genomic safe harbors where transgenes can be expressed without affecting host cell function.

New Data Point to Nuanced Relationship Between Major Depression, Bipolar Disorder

Lund University researchers in JAMA Psychiatry uncover overlapping genetic liabilities for major depression and bipolar disorder.