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Indi Molecular Building Discovery Platform With Fresh Series A Financing

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NEW YORK (360Dx) – Indi Molecular said this week it has closed an $11.5 million Series A financing round led by Merck Ventures, Legend Capital, Sabey Corporation, and existing investors.

The company plans to use the funds to build a high-throughput platform for discovering and developing its protein catalyzed capture (PCC) affinity agents and to move existing compounds with potential use in PET immuno-oncology imaging to the clinical stage.

A spinoff of proteomics firm Integrated Diagnostics, Indi Molecular launched as a separate entity in September 2013 with $1.8 million in seed funding from investors including InterWest Partners and Asset Management Ventures. It was formed to commercialize the PCC technology, which was developed in the lab of California Institute of Technology researcher James Heath, one of the company's cofounders.

PCCs use click chemistry combined with pairs of random peptide libraries — one containing acetylene functionalities and the other containing azide groups — to create affinity reagents to given proteins. Target proteins are screened against these libraries to find peptides that bind them, and when these peptides bind, the protein epitope acts as a catalytic point for the acetylene- and azide-containing peptides, which then link together via click chemistry, forming multipeptide, protein-binding constructs that can then be pulled down and identified.

According to Indi, the PCC agents offer several potential advantages over conventional affinity reagents like monoclonal antibodies, including better specificity, as well as the ability to target regions of proteins not accessible to monoclonals and to target proteins inside living cells, which can be a challenge for antibody-based reagents and drugs.

Indi Molecular planned initially to focus on developing PCCs for use as therapeutics, but funding difficulties forced it to concentrate more on establishing the molecules as potential affinity reagents for biological research and in vitro diagnostics. In 2014, the company inked a codevelopment deal with Sigma-Aldrich to explore the use of the PCCs as protein research reagents.

Even at that time, though, the company was shifting its focus back toward therapeutics, and this remains its current emphasis, though its PET imaging program indicates it continues to pursue diagnostic applications, as well.

The PET imaging and therapeutic applications are united by what CEO Albert Luderer said was a focus on moving their compounds into use in humans. He said the company hoped to demonstrate safety and efficacy in humans for its PET immuno-oncology reagent within the next 12 to 14 months.

The company's focus on high-value targets like therapeutics has been to an extent necessitated by the time and expense currently required to generate the PCCs, Luderer said, noting that one benefit of developing a high-throughput discovery platform would be that it could make the technology feasible as a more broadly used affinity reagent.

"We've been forced [thus far] to really work on super high-value targets," he said. "By increasing our lab throughput, we can go to a little more generalizable target and really extend the reach of the technology. That's a big goal."

Currently, development of a PCC takes around three months, and, Luderer said, given that the work is currently all done by Ph.D.s, "it's really expensive."

There are several sticking points that make the current discovery process time and resource intensive, Luderer said. One is building the bead-based PCC compound libraries to screen against targets of interest. To identify true interactions, the researchers have to eliminate nonspecific reactions triggered by, for instance, certain reagents used in the workflow.

"That has been a manual process," Luderer said. "It takes days and days to find out what is reacting [nonspecifically] and then pluck those beads physically out of this million, two million bead mix. It's a terrible process."

With the recent funding, the company plans to move to a flow cytometry-based system that will significantly speed this portion of the workflow, he said.

Another challenge has been sequencing the peptides in the PCCs that are true interactors to identify their composition. Here, the company will implement a system its researchers have developed to move directly from the target bead to a mass spectrometer, which will sequence the peptide of interest, Luderer said.

Additionally, the company is implementing a high-throughput system for assessing how candidate PCCs perform against the actual targets. "We'll be able to do hundreds of reactions simultaneously, get titration curves, assess specificity, and do it in a way that knocks them off one after another," he said.

Altogether, these improvements in process should bring PCC discovery and development times down to around three to four weeks, Luderer added. And, he noted, because the reagents are generated using routine peptide chemistry, scaling up production should be relatively inexpensive.

Even as costs and production times come down, though, the company plans to remain focused on high value therapeutic and imaging targets, as opposed to pursuing the broader research reagents market, Luderer said.

He noted that in addition to the PET immuno-oncology PCC, the company is also working on another imaging target for a different pharma partner that could potentially be used as a therapeutic, as well.

"It would combine the ability to image to track response, and also, using a different dosage regiment, to potentially use it as a therapy," he said.

Indi Molecular also recently submitted for publication a study on a PCC agent it developed to interleukin 17A, which is a drug target in advanced plaque psoriasis. The company developed a molecule capable of targeting this protein with 100 to 200 picomolar binding, Luderer said.

"We don't take it to the therapeutic implications because we didn't have enough money to do that, so we just stopped it there at the chemistry," he added. "Hopefully we'll get some partners for that."

Based in Culver City, California, Indi Molecular currently has four employees, a headcount it plans to double this year, Luderer said.

As part of the financing announced this week, Andreas Jurgeit from Merck Ventures and Darren Cai from Legend Capital will join the company's board.