ROCK1 x ROCK2

Sanofi’s strategic investment in Graviton Bioscience will advance the development of ROCK2 inhibitors. Credit: Gorodenkoff / Shutterstock.com. Graviton Bioscience has secured a strategic investment from Sanofi to develop a selective Rho/Rho-associated coiled coil [a structural motif in proteins] containing protein kinase 2 (ROCK2) inhibitors for serious diseases. The collaboration grants Sanofi the right of initial negotiation to license compounds for conditions, including immunological and metabolic syndrome indications. ROCK2 is part of the AGC family of kinases and an effector of the small guanosine triphosphate Rho. It is associated with the pathology of metabolic, autoimmune, inflammatory and neurological disorders, many of which currently lack adequate treatment options. Graviton Bioscience CEO and founder Samuel Waksal stated: “We are thrilled to welcome Sanofi as a strategic partner. Their dedication to the development of ROCK2 inhibitor treatments aligns perfectly with our vision. See Also: LimmaTech secures funding for vaccine technology development Tyra Biosciences’ TYRA-300 gains FDA rare paediatric disease status “This investment opens an exciting new chapter for our vision of advancing and commercialising ROCK2 inhibitors, fostering a future that holds promise for patients globally. We are enthusiastic about the support from Sanofi.” Graviton is committed to creating therapeutics for autoimmune, CNS, fibrotic and other serious diseases in which ROCK2 and its therapeutic compounds are crucial. The company’s drug candidate, GV101, is undergoing clinical trials while other assets are progressing through preclinical development. GV101 stands out as a clinical-stage selective inhibitor of ROCK2, with an ability to penetrate the blood-brain barrier evidenced in preclinical studies. It is now in a Phase I multiple ascending dose trial with healthy subjects and has shown clinically relevant exposure and a favourable safety profile. A different formulation of GV101 concluded a Phase I single and multiple ascending dose study in China. The drug demonstrated a favourable safety profile at clinically relevant exposures. Sanofi CEO Paul Hudson stated: “This investment in Graviton Bioscience reflects our commitment to innovative therapies and providing patients with novel medicines and vaccines. “Graviton’s scientific expertise in discovering and developing the next wave of innovation has the potential to significantly enhance the landscape of therapeutic possibilities.”

The clinical stage biotech made the announcement about its oral, selective, rho associated coiled-coil containing protein kinase (ROCK2) today (August 21). The drug is currently in a phase 2a clinical study for IPF with topline data expected in the first quarter of next year (2024). The FDA can grant ODD to support the development and evaluation of new treatments to prevent, diagnose or treat a rare disease or condition that affects fewer than 200,000 in the US. IPF - unmet need for patients The designation provides Redx with various development and commercial incentives, including market exclusivity, in order to address this unmet need for patients suffering from IPF. Dr Jane Robertson, chief medical officer, Redx Pharma said: “We are delighted that the FDA has recognised the potential of zelasudil for the treatment of IPF and granted Orphan Drug Designation. “Selectively targeting ROCK2 is an exciting, novel approach which could provide a new treatment option for patients with IPF, and with potential applications in other interstitial lung diseases and cancer-associated fibrosis. “We are encouraged by both the strength of our preclinical package as well as the clinical results to date and we look forward to reporting Phase 2a topline data in the first quarter of next year.” Zelasudil is an orally available, highly selective small molecule inhibitor that targets ROCK2 which sits at a nodal point in a cell signalling pathway, believed to be central to fibrosis. ROCK2 selectivity is important to avoid systemic hypotension, a serious cardiovascular side effect which has been seen in product candidates that systemically inhibit both ROCK1 and ROCK2. googletag.cmd.push(function () { googletag.display('text-ad1'); Potential to treat several fibrotic diseases As a selective ROCK2 inhibitor zelasudil, has the potential to treat several fibrotic diseases and has demonstrated robust anti-fibrotic effects in a range of industry-standard in vivo preclinical models, results of which were presented at the International Colloquium on Lung and Airway Fibrosis (ICLAF) and the Antifibrotic Drug Development Summit (AFDD) last year (2022). Redx is evaluating zelasudil initially as a treatment for IPF, a severe and life-threatening chronic lung condition with limited treatment options. IPF is a lung disease that causes scarring and reduction in lung function slowly over time. Primarly older adults mainly aged 50 and over get the disease which involves irreversible and variable scarring, stiffening, and thickening of the lung tissues leading to sufferers experiencing shortness of breath and lack of oxygen absorption. There are more than 170,000 people suffering from IPF according to Redx’s research with a further 53,000 people diagnosed every year in the US, five EU countries and Japan. The company says patients diagnosed with IPF have an estimated life expectancy of 3 to 5 years. There is no known cure and current treatment only slows progression of the disease.

The company that focuses on discovering and developing novel, small molecule, targeted therapeutics for cancer treatment and fibrotic disease announced additional preclinical data for its inhibitor, RXC007, along with the discodin domain receptor (DDR) 1/2 discovery program. This was presented at the resistant tumor microenvironment keystone symposia in Vancouver. The data was from preclinical models of PDAC and TNBC in combination with chemotherapy and immunotherapy, the current standard of care. RXC007, in combination with gemcitabine/Abraxane in metastatic and high-extra cellular matrix (ECM) patient-derived PDAC models, was shown to increase survival compared to single agent standard of care alone. The combination of RXC007 with standard of care provided a significant increase in median survival days from date of treatment in a dose dependent manner. Colloboration partner, the Garvan Institute of Medical Research, also presented data on close analogue REDX10616 at a congress last year (2022). These data show REDX10616 in combination with the standard of care triplet chemotherapy. The company says that taken together these data provide a strong rationale for the potential of ROCK2 inhibition Rho kinase (ROCK) signal transduction pathways (chains of molecules that relay signals inside the cell) are implicated in the development of fibrosis. Research has indicated that inhibition of the ROCK isoforms, ROCK1 and ROCK2, has shown promise in fibrosis but that ROCK1 inhibition has been associated with inducing hypotension. googletag.cmd.push(function () { googletag.display('text-ad1'); The company said that taken together, these data provide a strong rationale for the potential of ROCK2 inhibition