The Life Sciences Greenhouse of Central Pennsylvania this week said it has invested $250,000 in State College-based Indigo Biosciences, which has developed nuclear-receptor assays for use in drug discovery.
An Indigo official told CBA News this week that the firm will use the money to market its first product, a suite of frozen, single-use, cell-based, nuclear receptor assays designed to enable investigators to identify potential off-target effects of small-molecule drug candidates.
Until now, Indigo has used the assays in a contract research capacity, and the company is “in the process of rolling out the first products in our frozen, whole-cell, single-use nuclear receptor assay product line, so we will put a lot of [the Greenhouse] money towards marketing,” said Indigo CEO H. Dean Bunnell.
According to Indigo’s Chief Technology Officer Bruce Sherf, the company had “decided that it is time to try to make this into a product to try and satisfy that demand, and ship the product to them, and let [the customers] do their own assays.”
Bunnell and Sherf said that the company plans to launch the assay kits in January into the relatively nascent consumable assay kit market.
The assays are pre-formatted and prepared using Indigo’s proprietary cryopreservation technology, called CryoMite, which allows the assay to be stored at -80° C while preserving cell viability.
“Basically, it allows us to take our reporter cells and freeze them down to single-use aliquots that we can ship out with a kit,” said Sherf.
The end user then thaws the cells and runs the assay. The cells can be dispensed directly into 96- and 384-well format assay plates. They have full activity, and do not need further processing in terms of washing away reagent or putting in new media.
The cells “come back with 90 to 95 percent viability,” said Sherf. “It’s basically a cell-based reagent without any need to further manipulate them.”
He said scientists can use the kit to look at on-target as well as off-target activity. “We can also look at the other biological activities of a nuclear receptor that may be interrupted by an interaction with a compound,” he said.
Prospective customers have beta tested the assays, and produced promising results, said Steve Carpenter, vice president of venture operations at LSGPA. He also told CBA News that, “leadership of the company is a critical function, and with Dean Bunnell in place, we have very high confidence in them.”
“[The cells] come back with 90 to 95 percent viability. Its basically a cell-based reagent without any need to further manipulate them.”
Carpenter also said that Indigo’s CryoMite is “a unique technology that essentially satisfies some of the issues related to nuclear receptor assays [and] that other competitors have not been able to provide.”
He added that LSGPA believes that nuclear receptor assays are becoming “more and more popular” in drug discovery. “I think that they [are] offering a niche product, but the extent to which it gets adopted is obviously still a question,” Carpenter said.
According to Sherf, the firm’s kits “allow people to maintain the security of their IP by testing materials in house.” They do not have to send materials out.
According to Sherf, Indigo will still probably do a small amount of service work, but “we think that there is more opportunity in the product-based side, because we have seen the need for this type of assay from a number of our customers.”
The kits will be formatted in 96-and 384-well assay plates, said Sherf. They will include everything necessary to run the assay, including a positive control agonist for the receptor, the reporter cells, the media needed to dilute the test compounds, a detection reagent, and the plate itself. These will be configured for both 96-well plates and 384-well plates.
“Right now, in our very first early iteration of these products, we are envisioning going with just a single kit, and also a bulk pack, which would be the equivalent of about 10 kits,” said Sherf.
Bulk packs will be much more attractive to pharmas that are doing HTS, because they can plug the kits into their HTS facilities, said Bunnell, so “bulk reagents will definitely be a part of our product line up.”
The kits comprise “immortalized mammalian cells” that are both of human and non-human origin, said Sherf, declining to elaborate.
Over the next several years, “we want to continue to flesh out the single receptor assays in the nuclear receptor family,” said Sherf. One of the things that Indigo plans to do downstream is put together assays that have multiple nuclear receptors in them — “panels if you like,” Sherf said.
Bunnell said that Indigo will definitely be market-driven. “We want to pay attention to what people need, and not decide ourselves what we want to do, but rather, what the need is out there.”
In May, Indigo received $250,000 from Penn State’s Garber Venture Capital Fund.
Highly Druggable Targets
Indigo’s products will compete with Invitrogen’s GeneBLAzer kits and DiscoveRx’s eXpress product line. From a technology standpoint, nuclear hormone-receptor assays, which have been available for more than 10 years, have been in-house reporter-gene assays, as opposed to kits, said Sailaja Kuchibhatla, senior vice president of business development for DiscoveRx.
She mentioned that the company has GPCR kits, and will soon come out with the NHR kits as well.
“However, the downstream events from NHR-signaling that people are capturing in NHR assays lead to a lot of false positives; you have to wait for a long time to get those things done — 24 to 48 hours — and then look at the data downstream,” Kuchibhatla said.
She added that the availability of assay kit technology and of cell lines that investigators can use in their own labs without extensive instrumentation is stimulating renewed interest in NHRs.
Kuchibhatla also pointed out that NHRs are highly druggable because they are close to the membrane and very specific. So “they tend to be quite open to generating drug molecules against them, and people are coming back to them,” she said.
Ready-to-use assay kits do not require dedicated teams to develop them in house, Bunnell said. He added that for the most part, the pharma industry is currently developing assays in house.
However, “we have seen a significant amount of interest in this type of product,” he said.
These kits will get to play in an emerging market, said Kuchibhatla. “I think it’s only been about a year or 18 months since companies started servicing this particular space — single-use, consumable technologies.”
“We have presented our eXpress products to customers, and, by far, they love the concept” because the kits take cell biology and cell-based assays, which is the mainstay of assay development in a high-throughput screening campaign, and allow high-throughput scientists to do the same thing that cell biologists and R&D lead optimization teams are doing, without having to know how cells behave, said Kuchibhatla.
“These people are not cell biologists by training, yet they want to have the same technologies that these other people are using,” she said.
Kuchibhatla said this shift resembles one with biochemical screening, which has largely been replaced with cell-based assays. Likewise, assay kits made by Invitrogen, DiscoveRx, and Indigo could change downstream drug discovery, Kuchibhatla said.