By Doug Macron
Start-up Rana Therapeutics this week announced that it has raised $20.7 million in a Series A round of financing, which the company hopes will allow it to advance a lead drug candidate into investigational new drug application-enabling studies around the end of this year.
According to Rana President and CEO Art Krieg, the 12-employee company has obtained very promising data with its core gene-activation technology in both in vitro and in vivo studies.
“Because of the success of the initial experiments, we're seriously considering expanding faster than we had originally planned,” he told Gene Silencing News this week. He expects the firm could be ready to begin generating the data needed for an IND filing for its first drug candidate by year-end.
Still, he cautioned that such a timeline “would require everything to go perfectly smoothly, and that is seldom the case.”
Rana was founded last year with undisclosed seed funding from venture capital firm Atlas Ventures to develop a gene-activation approach developed at Massachusetts General Hospital. Krieg, formerly the head of Pfizer's oligonucleotide therapeutics unit, has been serving as an entrepreneur in residence at Atlas.
According to Krieg, Rana's technology involves blocking the interaction between a protein complex called polycomb repressive complex 2, or PRC2, and a long non-coding RNA.
“Long non-coding RNAs, of which there are many thousand in the genome, function in a variety of ways to regulate gene expression,” he explained. “One of the ways that the long non-coding RNAs systematically suppress gene expression across a lot of the genome is by interacting with ... PRC2, which modifies histones in a locus-specific fashion that suppresses transcription from chromosomal loci.”
As the lncRNAs are being transcribed from DNA and are tethered to the chromosome, they can bind with PCR2, which modifies the histones, Krieg said.
“With our technology, we prevent that PRC2 recruitment with oligonucleotides targeted to the long non-coding RNA,” he added. “That allows us to up-regulate gene regulation at specific chromosomal sites.”
Specific details about Rana's technology, which was developed in the lab of Massachusetts General Hospital's Jeannie Lee, remain undisclosed given its nascence. Krieg said that the company is currently evaluating which lncRNAs might make the most appropriate targets, as well as different chemistries and designs for drug candidates.
“We think the way we design the oligos is key to our success, and that's a part of our platform that hasn't been disclosed,” he said. “There is no benefit … to disclosing too much … too early … [but] we will be telling more about the technology as we get further along.”
He did say that the company has thus far tested oligos against 15 different targets “and we've succeeded” with all of them.
“The median level of up-regulation that we've seen at the RNA level in vitro is about four fold,” he said. “In vivo ...we saw four to eight-fold up-regulation in protein expression for the target.”
He noted that the in vivo experiments involved subcutaneous delivery of the oligos in saline, and that Rana isn't using “any complicated delivery systems; we're working with the natural pharmacokinetics of oligonucleotides.”
As for indications where the company's technology might be best suited, Krieg said that the gene-activation approach shows potential across "essentially" all disease areas
“If we wanted to use this for oncology … [assuming] that the oligonucleotides get into the tumor with acceptable [pharmacokinetics] … you could up-regulate tumor suppressors, you could up-regulate endogenous anti-angiogenic factors,” he said. “Conversely, we can use this to treat autoimmune diseases by up-regulating immune suppressive factors endogenous, or to treat various genetic diseases by up-regulating the factors that are defective.”
Rana has not yet selected lead indications, and Krieg said that this decision is expected to be made with the input of a partner as the company courts various pharmaceutical firms that might be interested in staking an early claim to the technology in the form of a discovery collaboration.
In addition to its promise in human therapeutics, Rana's technology might also prove useful in the agricultural biotechnology space.
“Plants also have PRC2 complexes and many long non-coding RNAs that are involved in epigenetic gene regulation,” Krieg said. As a result, Rana's technology could potentially be used to up-regulate genes that confer desirable traits in plants.
Although Rana is focused on drug development, the company holds the rights to the use of the gene-activation technology for ag-bio applications and would consider licensing it to interested parties, he noted.
Although it has not publicly stated in interest in Rana's technology, Monsanto took part in the Series A financing round. Additionally, about a year ago it struck an alliance with Atlas Ventures under which the two are identifying “strategic investments in a number of technology focus areas within agriculture.”
Also participating in Rana's Series A was SR One and Partners Innovation Fund.
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