TRPC5

Neurological drugs developer Karuna Therapeutics is building up its pipeline with a pair of molecules initially developed for kidney disorders. It’s a small bet that could pay off in a big way by diversifying its pipeline with medicines that could compete against a Boehringer Ingelheim drug candidate addressing the same target. The new Karuna assets come from startup Goldfinch Bio, which is shutting down. According to financial terms announced Thursday, Boston-based Karuna is paying $15 million up front for both small molecules. Goldfinch discovered drugs with technology that analyzed anonymized human kidney data in order to identify potential drug targets. That technology identified ways to target transient receptor potential canonical (TRPC) channels 4 and 5, pathways associated with certain kidney disorders. The research yielded lead program GFB-887, which reached mid-stage testing. While activity was shown in the kidney, Karuna President of Research & Development and Chief Scientific Officer Steve Paul notes that the preclinical and clinical research also showed antidepressant and anxiety-reducing properties. “We are fortunate to have found as advanced a clinical-stage drug candidate directed against these important [central nervous system] targets and we will now study GFB-887 in various mood and anxiety disorders where there remains a significant unmet medical need for mechanistically novel medicines,” Paul said in a prepared statement. Going after TRPC 4/5 brings a different dimension to Karuna, which has focused its research on targeting muscarinic receptors found in the central nervous system. Lead drug candidate KarXT, an agonist of two muscarinic receptors, M1 and M4, reached Phase 3 testing in schizophrenia. After posting positive data in the study last August, the biotech said it planned to seek FDA approval in mid-2023. The remaining programs are preclinical and are in development for undisclosed targets. Karuna said it expects to report more details on the plans for GFB-887 in the second half of this year. By then, Boehringer Ingelheim could have Phase 2 data for its drug candidate targeting TRPC4/5 in depression. A positive result in that study could read through to Karuna’s new assets, William Blair analyst Myles Minter wrote in a research note. He added that to his knowledge, Karuna now has the only other TRPC4/5 inhibitors in development for neuropsychiatric disorders and it could have a dosing edge—once daily compared to the twice-a-day dosing of the Boehringer Ingelheim drug candidate. The $15 million upfront payment is minor for what has the potential to become a high-value asset, Minter said. Depending on the progress of the research, Karuna could pay up to $520 million in milestone payments for each TRPC4/5 drug candidate. The biotech would also pay the Goldfinch estate royalties from sales if the molecules reach the market. Goldfinch, which spun out of venture capital firm Third Rock Ventures, initially tested GFB-887 in focal segmental glomerulosclerosis (FSGS), a rare disorder that leads to scar tissue on renal glomeruli, the parts of the kidney that filter waste from the blood. Nearly a year ago, the company reported mixed preliminary Phase 2 data for the drug. While the results showed reductions in levels of urine proteins indicative of FSGS, no treatment effect was observed in the initial group of diabetic nephropathy patients. Fierce Biotech was first to report last week that Goldfinch was shutting down. Executives told Fierce that the move follows the company’s failure to secure additional financing.

Karuna Therapeutics is potentially betting hundreds of millions of dollars on the idea that a shuttering drugmakers experimental medicines for kidney diseases could become useful treatments for psychiatric and neurological disorders.Through a deal announced Thursday, Karuna will get an exclusive global license to develop, manufacture and market these medicines from Goldfinch Bio, which target a type of protein known as transient receptor potential channels. Goldfinchs most advanced drug, GFB-887, has been studied in mid-stage clinical trials that tested it across several kidney illnesses, including diabetic nephropathy and focal segmental glomerulosclerosis.According to reporting from Fierce Biotech, Goldfinch is going out of business after failing to secure additional funding. The Cambridge, Massachusetts-based company launched in late 2016 with $55 million from Third Rock Ventures and a mission to usher in a new era of therapeutic development targeting the molecular basis of progressive kidney diseases.Goldfinchs work later attracted the attention of Gilead Sciences, which, in the spring of 2019, agreed to a multiyear collaboration focused on diabetic kidney disease as well as orphan kidney disorders. The heavily backloaded agreement carried a nearly $110 million upfront payment for the smaller company.About a year after announcing the Gilead deal, Goldfinch secured another $100 million in a financing round led by Eventide Asset Management. Gilead also participated in the round, as did new investors like Wellington Management and Ally Bridge Group.Yet, like many biotechnology companies with big ambitions, Goldfinch has faced setbacks. Last year, for instance, one of the studies testing GFB-887 delivered mixed results. And since then, a historic downturn in the biotech sector made it far more challenging for Goldfinch and many others to raise money.“Unfortunately, we had funding challenges, just like I think the rest of the environment, particularly private companies, in the current macro environment,“ Tony Johnson, Goldfinchs CEO, told Fierce Biotech.With the Karuna deal, Goldfinch, through the assignee of its assignment estate, will receive $15 million upfront. It is also eligible for up to $520 million in milestone payments for each candidate that gets licensed.Specifically, the deal gives Karuna access to drugs directed at the protein channels TRPC4 and TRPC5, which the company believes could have beneficial applications in the brain. Karuna said it intends to study GFB-887 for the treatment of mood and anxiety disorders, and will share more details on the drugs development plans in the second half of this year.So far, Karunas research efforts have largely revolved around KarXT, an experimental therapy that clinical trials showed to be helpful in the treatment of schizophrenia. Karuna expects this year to ask the Food and Drug Administration to approve KarXT, and is also evaluating the therapy in patients with Alzheimers disease psychosis.Goldfinchs medicines therefore help to diversify Karunas research.We believe that the TRPC4/5 mechanism could represent a completely novel approach to treating mood and anxiety disorders and complements our existing pipeline, Bill Meury, Karunas newly minted CEO, said in a statement.Meury added that the Goldfinch agreement aligns with our strategic goal to become a fully integrated neuroscience company with treatments that could offer much more than just incremental benefits to patients. '

July 7, 2022 12:00 UTC -- Company shares proprietary and scalable approach using human derived organoids for preclinical pharmacodynamic (PD) assessment of drugs targeting podocyte cells -- -- Recent preliminary data from Phase 2 study of GFB-887 in focal segmental glomerular disease (FSGS) further validate feasibility and value of using transplanted human organoids in preclinical PD studies -- CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Goldfinch Bio, Inc., a clinical stage biotechnology company focused on discovering and developing precision medicines for the treatment of kidney diseases, today announced the publication of data validating transplanted, perfused human kidney organoids as a novel, predictive and translatable preclinical PD model for use in kidney disease drug development. This breakthrough approach was initially validated with the company’s lead drug candidate, GFB-887, a selective Transient Receptor Potential Canonical Channel 5 (TRPC5) inhibitor, which, since this original organoid work, demonstrated clinical proof of concept in a Phase 2 study in patients with FSGS. The manuscript, titled “Transplanted organoids empower human preclinical assessment of drug candidate for the clinic,” is available online in the international peer-reviewed journal Science Advances at: . “Since the start of Goldfinch Bio, we have been committed to using human organoids to improve the preclinical drug development process in kidney disease, which has lacked adequate and reliable tools to date. Our belief in the use of organoids was initially validated using GFB-887 in a human organoid model of podocyte injury, and the recent preliminary data from our ongoing Phase 2 trial of GFB-887 for FSGS demonstrates the successful clinical translation of our approach,” said Anthony Johnson, M.D., President and Chief Executive Officer at Goldfinch Bio. “We believe our pioneering approach is applicable across an array of tissues and organs, and we look forward to sharing our findings with the broader drug development community in hopes of ushering in a new era of more translatable preclinical models and, ultimately, more efficient drug discovery.” A key challenge in modern drug development is the limited predictive power and translatability of PD studies in animals to relevant patients, which makes it difficult to accurately assess the potential efficacy of novel therapeutic drug candidates preclinically. To address this shortcoming, Goldfinch Bio scientists developed a novel, scalable approach for in vivo PD studies that leverages human tissue in the form of induced pluripotent stem cell (iPSC)-derived kidney organoids. The Science Advances manuscript outlines new insights gleaned from Goldfinch Bio’s preclinical study of GFB-887, including when best to transplant organoids to optimize vascularization, perfusion and differentiation, and the preferred method for organoid profiling and quality control. As described in the Science Advances publication, and as previously presented at the 13th International Podocyte Conference, Goldfinch Bio used human-derived organoid systems to establish preclinical efficacy for GFB-887, the Company’s highly potent and selective inhibitor of TRPC5. In February 2022, Goldfinch Bio announced treatment with GFB-887 in an ongoing Phase 2 clinical trial demonstrated a statistically significant, clinically meaningful 32% placebo-adjusted mean reduction in urine protein creatine ratio (UPCR) in patients with FSGS. About Goldfinch Bio Goldfinch Bio, Inc. is a clinical stage biotechnology company focused on delivering disease-modifying precision medicines that bring hope and renewed quality of life to people living with kidney diseases. We aspire to save kidneys and end dialysis. We have a robust pipeline of novel, precision medicine product candidates targeting kidney diseases with significant unmet need, including two clinical-stage assets. Visit us at to learn more.