Coming out of stealth mode, Ribon Therapeutics Inc. secured a $65 million series B financing round, adding to the $43 million series A the company raised in November 2015, to advance its pipeline of drugs targeting monoPARPs, a subset of 12 members of the poly ADP-ribose polymerase (PARP) family.
"Our series B financing will enable us to move our lead program into the clinic as well as continue to progress our pipeline of additional programs," Victoria Richon, president and CEO of Ribon, told BioWorld, adding that the funding could be enough to get an additional program or two beyond its lead program into clinical testing.
The round was led by the Novartis Venture Fund, with participation from new investors Johnson & Johnson Development Corp. and Celgene Corp. Existing investors, The Column Group, Deerfield Management, U.S. Venture Partners, Osage University Partners, Takeda Ventures and Euclidean Capital also participated in the financing round.
"We're really excited by the interest we've had by the corporate funds in terms of building opportunities for the company in the future," Richon said of the potential for partnerships with one or more of the drug companies investing in the series B round.
Ribon, of Lexington, Mass., was founded by Paul Chang, who currently serves as Ribon's vice president of discovery biology, as well as W. Lee Kraus, who is a professor at UT Southwestern Medical Center, and Harvard Medical School professor Tim Mitchison to specifically look at the monoPARPs.
Other PARPs, including PARP1, which is a target of already-approved Lynparza (olaparib, Astrazeneca plc), Zejula (niraparib, Tesaro Inc.) and Rubraca (rucaparib, Clovis Oncology Inc.), add branched polymers that create a scaffold for recruiting other proteins to direct their function at specific sites within the cell. MonoPARPs, on the other hand, add a single unit of ADP-ribose derived from a NAD+ molecule, which modulates signal transduction pathways similar to phosphorylation by kinases.
"The nomenclature becomes confusing," Richon noted, since monoPARP is an oxymoron given that the first "p" in PARP stands for "poly," but she pointed out the family was grouped together and all given the PARP gene name because they have similar catalytic domains.
Outside of the catalytic domain the family members have different functional domains suggesting that they serve distinct functions in the cell. "That was one of the things that really interested us when we started the company," Richon said, noting that the PARP1 inhibitors gave the company confidence that it would be possible to inhibit the function of the other PARP family members.
For its lead molecule, Ribon has focused on PARP7, a monoPARP that is normally expressed at low levels but is activated under stress. PARP7 inhibits type I interferon production induced by damage associated molecular pattern (DAMP) recognition pathways, which has a direct role in cell survival and also allows the cancer cells to hide from both the innate and adaptive immune system.
"We think that both play a very important role in being able to see the antitumor effect," Richon said, adding that the company is continuing to explore the mechanism of action. In preclinical testing, Ribon's lead molecule has antiproliferative activity and produced durable tumor regressions in preclinical animal models.
Ribon is looking to move the PARP7 inhibitor into the clinic by the end of 2019, starting with squamous cell carcinoma of the lung, since PARP7 has been shown to be amplified in that tumor type. Based on the preclinical data, the company plans to begin clinical trials testing the drug as a monotherapy, but Ribon is also exploring possible synergies with immuno-oncology drugs that stimulate the immune system as well as standard chemotherapy drugs that induce cellular stress and induce DAMP recognition.
Ribon isn't disclosing the other targets it's going after, but Richon noted that the company is using its expertise in mechanistic biochemistry and structural biology to branch out beyond monoPARPs to other molecules that use NAD+ as a substrate. Beyond cancer, the stress protecting proteins could play roles in neurodegeneration and inflammatory diseases.