Ractigen feeds its pipeline of candidate medicines through our in-house Discovery Engine with support of oligonucleotide medicinal chemistry and our delivery technologies.
Our pipeline and discovery engine focuses on genetically-validated gene targets known to be the cause and/or cure of numerous diseases. Ractigen’s pipeline includes internal and co-development projects that explore the boundaries of our technology and push for the next generation of RNAa therapeutics.
Our Strategic Therapeutic Area
Spinal muscular atrophy (SMA)
Spinal muscular atrophy (SMA) is genetic disease caused by homozygous loss of a gene called SMN1 (survival of motor neuron 1). SMN1 encodes for an essential protein called SMN (survival of motor neuron) that is necessary for proper function of motor neurons, which are predominately found the spinal cord of the CNS. Deficiencies in SMN impact motor neuron survival leading to progressive muscle weakness and atrophy.
A second gene called SMN2 is almost identical to SMN1, but only produces very low levels of functional SMN protein. In the absence of the SMN1 gene, SMN2 does not normally produce enough SMN protein to compensate for SMN1. However, by augmenting SMN2 expression via RNAa in the CNS, our RAG-06 program aims to boost SMN protein to levels capable of compensating for SMN1 loss and protecting motor neuron function in SMA patients.
Amyotrophic lateral sclerosis (ALS)
RAG-17 is a therapeutic siRNA designed to target and knockdown the expression of SOD1 in patients with pathogenic mutations known to cause ALS. The RAG-17 chemistry is based on Ractigen’s proprietary Smart Chemistry-Aided Delivery (SCAD) delivery platform, in which the siRNA is conjugated to an accessory oligonucleotide (ACO), enabling durable and potent activity in CNS tissues. Based on several preclinical studies, RAG-17 has a significantly higher potency on ALS disease models (e.g. hSOD1G93A mouse model) than benchmark compounds.
Duchenne muscular dystrophy (DMD)
DMD (Duchenne muscular dystrophy), caused by mutations of the dystrophin (DMD) gene on the X chromosome, is the most common and lethal pediatric muscle disorder without a known cure. It is fairly prevalent, with a frequency 1/3,500~1/6,000 in males, and an average life expectancy of just 26 years. BMD (Becker muscular dystrophy) is a minor form of DMD also resulting from a DMD mutation.
RAG-18 is a saRNA delivered to muscle tissue to increase UTRN expression and compensate for DMD defects regardless of the location of mutation on DMD gene. Delivery of saRNA to the muscle is achieved by Ractigen’s proprietary LiCO technology.
Non-Muscle invasive bladder cancer (NMIBC)
Non-muscle invasive bladder cancer (NMIBC) accounts for 70-80% of all bladder cancer diagnoses. Typical treatment includes transurethral resection of bladder tumor (TURBT) followed by repeated intravesical instillations of chemotherapy drugs or Bacillus Calmette-Guérin (BCG). Despite such preventive measures, a 5-year recurrence rate is still at 50-70%.
Our RAG-01 program is designed to target and restore expression of a tumor suppressor gene via RNAa typically silenced in bladder cancer cells. RAG-01 is intended to be better tolerated by patients during treatment and provide a superior response with reduced recurrence.
Disorders with Liver Targets
Thrombocytopenia refers to any disorder in which there is an abnormally low count of platelets in blood. Left untreated, thrombocytopenia can lead to uncontrolled bleeding and bruising. The protein thrombopoietin (THPO) is a hematopoietic growth factor secreted by the liver that protects megakaryocytes and stimulates platelet production. Persistent and chronic thrombocytopenia caused by liver disease, myelodysplastic syndrome (MDS), and autoimmunity often have inadequate levels of THPO. Our RAG-03 program is designed to stimulate production of THPO by the liver, enhance platelet count, and counteract persistent thrombocytopenia.
Acute intermittent porphyria (AIP)
Acute intermittent porphyria (AIP) is a rare genetic disorder that affects the production of heme; an essential cofactor of hemoglobin that is necessary for oxygen transport by red blood cells. AIP is caused by low levels of a metabolic enzyme called HMBS (hydroxymethylbilane synthase) in the liver (hepatic tissue) leading to the accumulation of toxic porphyrin precursors. Partial deficiencies in the HMBS enzyme arise from a genetic mutation in the HMBS gene in which only one copy of the gene is inactivated resulting in a haploinsufficiency. Most people with HMBS haploinsufficiency do not develop symptoms of AIP until presented with a possible “trigger” at some point in their lifetime (e.g., puberty, fasting, medications, stress, hormonal fluctuations, etc.) causing symptomatic acute porphyria. Our RAG-05 program aims to address haploinsufficiency of HMBS by boosting expression of the functional gene copy in liver of AIP patients via RNAa.
Hereditary angioedema (HAE)
Hereditary angioedema (HAE) is caused by C1-esterase inhibitor (C1-Inh) deficiency due to a mutation in a gene called SERPING1. HAE is a haploinsufficiency disorder in which only one copy of SERPING1 is inactivated resulting in partial C1-Inh deficiency. Subsequently, symptoms of HAE manifest as recurrent attacks brought on by different stimuli (e.g., minor trauma, stress, illness, physical exercise, etc.) leading to bouts of extreme swelling in extremities, face, larynx, and the digestive tract. Our RAG-12 program aims to address haploinsufficiency of SERPING1 by boosting C1-Inh production in the liver of HAE patients via RNAa to prevent recurrent attacks.
FVII deficiency/Hemophilia with inhibitors
Factor VII (FVII), aka proconvertin, is a clotting factor of the coagulation system and synthetized exclusively by the liver with extremely short half-life (4-6 hours). People with FVII deficiency can experience severe joint and muscle bleeds, as well as easy bruising and bleeds after surgery. Fresh plasma and recombinant factor VIIa (rFVIIa) have been used to treat FVII deficiency and hemophilia with inhibitors. However the rFVIIa needs to be administered frequently by IV infusion.
RAG-20 is a saRNA delivered to the liver by Ractigen’s proprietary GLORY technology to boost hepatic FVII production. It is being developed for the treatment of disorders such as hemophilia with inhibitors (incl. acquired hemophilia), FVII deficiency, and Glanzmann’s thrombasthenia.
Proliferative vitreoretinopathy (PVR)
Proliferative vitreoretinopathy (PVR) is an ocular condition that occurs after retinal detachment repair surgery or trauma to the eyeball that can lead to vision loss or blindness. PVR develops when proliferating cells form subretinal scar tissue that pull the retina away from the interior lining of the eye. There is no approved therapy for PVR despite a reported incidence up to 45% in people healing from perforating and penetrating wounds as well as being the most common cause for failure of retinal detachment repair surgery.
Our RAG-01C program is designed to boost expression of a cell cycle inhibitory gene in proliferating cells of the eye following surgery or injury via RNAa in order to stop development of scarred tissue and breaks in the retina. RAG-01C is intended to provide better surgical outcomes and limit the need for recurrent surgeries by preventing PVR formation.