The Salk Institute for Biological Studies

SAN DIEGO--( BUSINESS WIRE )-- Curebound , a philanthropic organization that invests in cancer research with the power to save lives, is ending 2024 with some impressive milestones – research investment of $43 million, $126 million in follow-on funding for 48 of its collaborative grants, 142-funded research grants, and 35 new or expanded clinical trials underway. The challenge: there are many promising cancer studies still left unfunded in the race to develop cures for cancer in our lifetime. Curebound is focused on cancer research using a venture capital model, making multiple smaller bets on early-stage innovative studies with talented research teams - and then providing larger follow-on grants for those seedlings that demonstrate greatest potential for near-term clinical translation and cures for cancers. But there is so much more to do, according to Curebound Chief Science Advisor Ezra Cohen, MD . “People are being diagnosed with cancer every day. But there are effective therapies for cancer that didn’t exist just a year ago that are benefiting patients today. Imagine where we will be a year from now, five years from now,” says Dr. Cohen. “We need to move fast, accelerate the pace, and invest in bold ideas, not just incremental steps.” Video of Curebound Chief Science Advisor Ezra Cohen, MD . Curebound impact: $43 Million Invested in Cancer Research $126 Million in Follow-On Funding Awarded to 48 Collaborative Grants 142 Innovative Research Grants Underway Exploration in 23 Types of Cancer 35 Clinical Trials Initiated 10 Companies Founded with Funding from Curebound Introduced Two New Research Grant Programs in 2024: Catalyst and Equity Announced Curebound Whitworth Legacy Circle Launched New Curebound Cancer Challenge August 2, 2025 – walk, ride, run, or spin Curebound is strategically headquartered in San Diego’s major U.S. biotech hub, amid 3,000+ life sciences companies, leading health systems, and world-class research institutions including its research partners Moores Cancer Center at UC San Diego, Salk Institute, Sanford Burnham Prebys, Rady Children’s Hospital, La Jolla Institute for Immunology, and Scripps Research. It is appealing to those with a vision of a world without cancer to join its mission to invest in cutting-edge science that can save lives. Give the gift of hope today .

A turbulent 2024 for Neurocrine is ending on a high note, after the biotech won FDA approval to treat congenital adrenal hyperplasia, a condition marked by adrenal gland dysfunction. The Friday decision gives Neurocrine its second approved product, behind its movement disorder drug Ingrezza. The new medicine, to be sold as Crenessity, is the first new treatment for classic CAH in 70 years, the company said. It’s also a milestone for late founder Wylie Vale, a scientist at the Salk Institute who spearheaded peptide hormone research and the relationship between the brain and the endocrine system. Vale, who died in 2012, identified the corticotropin-releasing factor that the new drug — also known as crinecerfont — works to block. The label includes both adults and children with CAH, following what Neurocrine says was the largest clinical trial in history for classic CAH. In kids, Crenessity helped reduce androstenedione hormone levels, which in turn decreased androgen and associated steroid use. Neurocrine reported similar findings in the adult study, reducing glucocorticoid dose levels by week 24, the primary endpoint. Shares of Neurocrine $NBIX jumped more than 5% after the markets opened Monday. William Blair analysts called the label “nonrestrictive” and believe the drug can do $150 million in 2025 US sales and hit a global peak of $1.47 billion in 2030. Neurocrine already launched an educational campaign earlier this year for the 20,000 to 25,000 people — adults and children — living with CAH in the US. It also snagged a priority review voucher with Crenessity’s approval, a hot-ticket item that other biotechs have sold for upwards of $150 million. The approval provides some momentum for Neurocrine after a volatile year. The biggest hit came in August after the company reported Phase 2 data from its muscarinic 4 agonist schizophrenia drug that appeared to fall short of results by Bristol Myers Squibb and Karuna Therapeutics’ now-approved option. Neurocrine’s schizophrenia candidate, NBI-’568, notched a statistically significant improvement in symptoms compared to placebo, but the difference was less than what Karuna reported in its late-stage clinical trial. The company’s shares plunged 20% after the results, though it plans to go ahead with Phase 3 testing. And luvadaxistat, another mid-stage treatment for cognitive impairment associated with schizophrenia, was culled this year after failing to reproduce prior encouraging data. But a licensing deal with Takeda showed signs of promise in April, after a novel depression treatment bested placebo on symptom improvement in a Phase 2 study among patients who did not respond to prior antidepressant treatment. Phase 3 studies are now slated for 2025.

Data demonstrate engineered tRNA from company’s first development candidate restores protein production to clinically meaningful levels in two disease models driven by the same premature termination codon CAMBRIDGE, MA, USA I December 9, 2024 I Alltrna , a Flagship Pioneering company unlocking transfer RNA (tRNA) biology and pioneering tRNA therapeutics to regulate the protein universe and resolve disease, today announced the presentation of new preclinical data, including of the company’s first tRNA development candidate, AP003. AP003 is a chemically modified, engineered tRNA oligonucleotide in a clinically validated, liver-directed lipid nanoparticle (LNP) that can readthrough the arginine to TGA (Arg-TGA) premature termination codon (PTC). A single dose of AP003 tRNA showed robust in vivo restoration of protein production to clinically meaningful levels in two transgenic Stop Codon Disease mouse models, methylmalonic acidemia (MMA) and phenylketonuria (PKU). The data were presented at the Nature Conference: RNA at the Bench and Bedside IV, taking place December 9-11 at The Salk Institute in La Jolla, California. “These data represent an important milestone for Alltrna, demonstrating robust in vivo activity and clinically relevant protein restoration across two disease models representing two different inborn errors of metabolism driven by the same premature termination codon,” said Michelle C. Werner, CEO of Alltrna and CEO-Partner at Flagship Pioneering. “We believe these data support the potential for a basket approach to developing AP003 for the treatment of many rare genetic liver diseases caused by an Arg-TGA PTC, including the organic acidemias and aminoacidopathies represented by our MMA and PKU Stop Codon Disease mouse models. We look forward to advancing our IND-enabling studies for AP003.” In an MMA Stop Codon Disease mouse model, developed by Alltrna and collaborators, a single dose of the tRNA component of AP003 (tRNA-3) in a LNP delivery system restored in vivo protein levels of methylmalonyl-CoA mutase (MMUT) to approximately 25% of wildtype levels at Day 4, well above the 1-2% protein rescue considered to be clinically meaningful in MMA by key opinion leaders. Protein levels remained above 1-2% of wildtype 14 days after dosing, which was the longest time point tested. In a new Stop Codon Disease mouse model of PKU, developed by Alltrna, a single dose of AP003 demonstrated phenylalanine hydroxylase (PAH) restoration to 7% of wildtype levels within 72 hours, exceeding the clinically relevant 3% protein rescue target defined by key opinion leaders. Further, this PAH protein restoration resulted in a meaningful 76% reduction of phenylalanine (Phe) levels from baseline, as PAH is the enzyme responsible for breaking down Phe. When PAH is mutated or deficient, Phe accumulates to toxic levels, causing the hallmark elevated Phe levels observed in PKU. “Based on tRNA’s critical role in protein translation, a single tRNA medicine is uniquely positioned to address multiple diseases that have a shared mutation. We are excited to see that our engineered tRNA can in fact achieve significant restoration of protein production above clinically relevant target levels in both MMA and PKU, where a premature termination codon would otherwise create a truncated or missing protein,” said Chris Henderson, Ph.D., Chief Scientific Officer of Alltrna. “In addition, to our knowledge, these are the first preclinical data with a tRNA candidate demonstrating that protein restoration leads to meaningful changes in levels of a clinical biomarker (Phe) that is recognized as a registrational endpoint in humans.” Dr. Henderson continued, “We are delighted to have generated such promising in vivo data in two models of Stop Codon Disease. The fact that a single engineered tRNA acting on the same premature termination codon can show readthrough and protein restoration in two distinct genetic contexts provides support for Alltrna’s vision of treating patients carrying the same PTC across different diseases in a given tissue. As a first example, we look forward to developing AP003 through a basket approach as a novel treatment for inborn errors of metabolism affecting the liver.” About AP003 AP003 is a chemically modified, engineered tRNA oligonucleotide encapsulated in a clinically validated, liver-directed lipid nanoparticle that is in development for the treatment of patients with liver Stop Codon Disease that carry an arginine to TGA (Arg-TGA) nonsense mutation in the affected gene. The Arg-TGA mutation occurs when a single base of the arginine-encoding codons, CGA and AGA, mutates to UGA (TGA in DNA), a termination codon for which there is no corresponding amino acid. AP003 is designed to readthrough the premature termination codon to reintroduce arginine into the growing polypeptide chain at the time of RNA-to-protein translation and restore protein production. Arg-TGA is the most frequent nonsense mutation (21-22%) occurring in human genetic diseases. About Stop Codon Disease Stop Codon Disease encompasses thousands of rare and common diseases that stem from premature termination codons (PTC) also called nonsense mutations, where the code for an amino acid has been mutated into a premature “stop” codon. This results in a truncated or shortened protein product with no or altered biological activity that causes disease. Approximately 10% of all people with a genetic disease have Stop Codon Disease, representing approximately 30 million people worldwide. Alltrna is engineering tRNA medicines that can read these PTC mutations and deliver the desired amino acid, thereby restoring the production of the full-length protein. About Alltrna Alltrna unlocks tRNA biology to treat disease. The company’s platform incorporates AI/ML tools to develop and deliver diverse programmable molecules with broad therapeutic potential. Alltrna has an unprecedented opportunity to advance a single tRNA medicine to readthrough premature stop codons and unify treatment across a wide range of diseases with the same underlying genetic mutations. Alltrna was founded in 2018 by Flagship Pioneering. For more info, visit www.alltrna.com . SOURCE: Alltrna