Janssen Tabs Start-Up Scholar Rock For New Immunology Approach
This article was originally published in The Pink Sheet Daily
Executive Summary
The J&J subsidiary has signed a deal with Boston-area Scholar Rock to discover new biologics that aim for a more pinpoint solution to inflammatory disease.
New drug discovery company Scholar Rock Inc. hasn’t yet raised a full round of venture capital, but it’s got biotech boldface names on its board and, as announced on Wednesday, Jan. 8, a discovery alliance with Johnson & Johnson’s Janssen Biotech Inc. in Boston.
The exclusive alliance centers on transforming growth factor beta 1 (TGF-beta 1), a cytokine found in many tissues and a key component of the immune system. Scholar Rock’s work is based on controlling how TGF-beta and other growth factors move from a dormant to an active state. Using biologics to activate dormant growth factors – or preemptively keep them dormant – could lead to a much finer-grained control of the body’s maddeningly complicated immune response. “The ability to control cytokines and their expression on a tissue or cell specific basis without the downside would be a major advance,” says Michael Elliott, vice president, immunology scientific innovation at the new J&J Innovation Center in Boston.
The “downside” is that the side effects of current anti-inflammatory drugs rather crudely tamp down the immune system; susceptibility to infection and increased risk of cancer are two issues. Elliott and others at J&J think Scholar Rock’s insights, based on work from the Harvard Medical School and Boston Children’s Hospital labs of Tim Springer and Leonard Zon, could help autoimmune treatments turn a corner.
It’s been known for a while that growth factors like TGF-beta 1 exist in a dormant state, and that several mechanisms can activate them -- as Scholar Rock CEO Nagesh Mahanthappa describes it, “let them out of their cages,” or more technically speaking, their prodomains. Proteases in the extracellular environment can “chew up” the prodomain cages, for example, or integrins can bind and “unlock” them – a particular focus of Springer’s work.
For a company named in honor of the traditional Chinese contemplation of aesthetically pleasing stones, structure is paramount. In its roughly 18-month existence, Scholar Rock has worked to elucidate structural comparisons between the growth factors in their active states, in their “caged” or dormant states, and when physically joined into complexes that include other so-called presenting molecules, whose presence affects the growth factors’ activity. “The way the ‘cage’ is presented in different tissues varies dramatically,” said Mahanthappa. “It might be unlocked only in wound healing, or in an immune context. Janssen wants to bring forward a therapeutic entity that can modulate the TGF-beta 1 cage in the immune system.”
TGF-beta 1 is a key control of undifferentiated regulatory T cells, pushing them generally to develop anti-inflammatory properties – but not always. Creating or restoring a balance in pro- and anti-inflammatory T cells could be a way to correct some immune diseases like rheumatoid arthritis, said Elliott. Learning how to release TGF-beta 1 only in the immune “microenvironment” of regulatory T cells could fight those diseases without affecting other cells or tissue types.
With dormant growth factors sequestered in the extracellular environment or on cell surfaces, Scholar Rock and Janssen aim to make novel biologics to wake them up – or keep them sleeping.
The firm announced January 2 that two biotech veterans joined the board, both with notable start-up experience. Michael Gilman was a top Biogen Inc. scientist who spun out a Biogen fibrosis candidate into Stromedix Inc. in 2007. He subsequently sold Stromedix back to Biogen Idec in 2012, stayed on to run early-stage development, then left in 2013 (Also see "Biogen Idec Buys Stromedix, Bringing IPF Candidate Full Circle" - Pink Sheet, 14 Feb, 2012.). Katrine Bosley was CEO of Avila Therapeutics Inc., where Mahanthappa was vice president of corporate development. They sold Avila to Celgene Corp. for $350 million upfront in 2012 (Also see "Celgene Bolsters Pipeline With Avila Acquisition" - Pink Sheet, 26 Jan, 2012.).
Janssen gets rights to any immune-modulated indication, which leaves Scholar Rock to pursue TGF-beta 1 modulators, either on its own or with a partner, in indications such as wound healing, fibrosis, and non-immunomodulated cancer. And it plans to go beyond TGF-beta, as well. Mahanthappa insists Scholar Rock will look for programs it can develop independently. “I don’t want it to be a research boutique that’s partnering each growth factor with different pharma partners, giving up rights at early stages,” he said.
Janssen was involved early, said Elliott, through its partnership with Polaris. “We’ve been talking to Springer and other founders for 18 months,” he said. Financial details of their deal remain undisclosed, but Mahanthappa calls them “quite outstanding for a discovery-stage program.” Scholar Rock gets research funding, with option and various milestone payments. Janssen does not have an option to acquire Scholar Rock, and it is not taking an equity stake.
Scholar Rock has raised seed money from Polaris Venture Partners and Springer, and Mahanthappa said there will be a financing in 2014.