Ractigen stands at the forefront of transforming RNA activation (RNAa) into a groundbreaking class of oligonucleotide therapeutics, designed for precise activation of target gene expression. Our pipeline targets diseases previously deemed undruggable, such as monogenic disorders like haploinsufficiencies, where RNAa can counteract or remedy reduced gene activity by enhancing transcription. Enabled by our proprietary SCAD™, LiCO™ and GLORY™ delivery platforms, our therapeutic scope currently spans the central nervous system (CNS), neuromuscular, ocular, liver, and oncology sectors.
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.
Therapeutic Area Key:
Program
Indication
Modality
RAG-18
Duchenne muscular dystrophy (DMD)
saRNA
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.
RAG-17
Amyotrophic lateral sclerosis (ALS)
siRNA
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.
An Investigator Initiated Trial (IIT) assessing RAG-17 in adult ALS patients with an SOD1 mutation has been completed, demonstrating positive safety and preliminary efficacy data. Based on these encouraging results, a Phase I clinical trial is now ongoing in China to further evaluate the safety, tolerability, and pharmacokinetics of RAG-17.
RAG-06
Spinal muscular atrophy (SMA)
saRNA
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.
RAG-01
Non-Muscle invasive bladder cancer (NMIBC)
saRNA
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.
RAG-1C
Proliferative vitreoretinopathy (PVR)
saRNA
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-1C 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-1C is intended to provide better surgical outcomes and limit the need for recurrent surgeries by preventing PVR formation.
RAG-24
Obesity
saRNA
RAG-24 is an saRNA therapeutic candidate aimed at treating obesity and related metabolic disorders. Delivered specifically to adipose tissue using Ractigen’s LiCO™ delivery technology, it works by activating a specific, undisclosed gene within this tissue. This gene is pivotal for promoting the activity of brown and beige fat, thereby increasing the body’s natural energy expenditure through enhanced thermogenesis, lipolysis, and fatty acid oxidation. Supporting this approach, preclinical proof-of-concept (PoC) studies using mouse surrogate saRNAs in Diet-Induced Obesity (DIO) mice demonstrated significant body weight control efficacy. Furthermore, these studies revealed an additive therapeutic effect when our saRNA was used in combination with a GLP-1 agonist. Beyond obesity, this mechanism shows promise for treating other metabolic conditions like diabetes, MASH (Metabolic dysfunction-associated steatohepatitis), and MASLD (Metabolic dysfunction-associated steatotic liver disease).
RAG-03
Persistent thrombocytopenia
saRNA
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.
RAG-05
Acute intermittent porphyria (AIP)
saRNA
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.
RAG-12
Hereditary angioedema (HAE)
saRNA
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.
RAG-20
FVII deficiency/Hemophilia with inhibitors
saRNA
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.
Non-muscle invasive bladder cancer (NMIBC) constitutes 70-80% of all bladder cancer cases. Typical treatments include transurethral resection of the bladder tumor (TURBT) followed by repeated intravesical instillations of chemotherapy drugs or Bacillus Calmette-Guérin (BCG).
Despite these interventions, the 5-year recurrence rate remains high at 50-70%, underscoring a substantial unmet need for more effective and less burdensome treatment.
A primary driver of tumorigenesis in NMIBC is the loss of tumor suppressor genes, particularly through disruptions in the p53-p21WAF1/CIP1 (p21) pathway. Addressing this pathway presents a promising approach to cancer therapy. RAG-01, a novel saRNA therapy developed by Ractigen Therapeutics, targets and activates the traditionally “undruggable p21 gene through the RNAa mechanism. By reactivating this key regulatory pathway, RAG-01 aims to prevent recurrence and impede progression of NMIBC. Promising results from preclinical studies have demonstrated that RAG-01 significantly suppresses tumor growth in mouse orthotopic bladder cancer models.
Administered through intravesical instillation, RAG-01 utilizes Ractigen’s proprietary LiCO™ delivery technology, which efficiently penetrates the glycosaminoglycan layer lining the urothelium and delivers the saRNA directly to the urothelial cells. This localized delivery method allows high drug concentration in the bladder urothelium while minimizing systemic exposure and potential side effects.
RAG-01 is currently in an open-label, dose-escalation, multi-center Phase I study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of RAG-01 in NMIBC patients unresponsive to BCG therapy.
Ractigen Therapeutics is at the forefront of developing saRNA drugs utilizing the RNA activation (RNAa) mechanism to up-regulate endogenous gene expression. RAG-01 is a pioneering small activating RNA (saRNA) drug engineered to target and activate the tumor suppressor gene p21 via the mechanism of RNAa. It is currently being investigated in a phase Ⅰ, open label, multi-center study in patients with non-muscle-invasive bladder cancer (NMIBC) who have failed Bacillus Calmette-Guérin (BCG) therapy. We are conducting the clinical trial aiming at gaining regulatory approval to make RAG-01 available to all eligible patients as quickly as possible.
Expanded Access, which is sometimes known as “compassionate use”, is a potential pathway for a patient with an immediately life-threatening condition or serious disease or condition to gain access to an investigational therapy for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available. The U.S. FDA advises that Expanded Access may be appropriate when all the following apply:
For more information about expanded access in the U.S., please visit the FDA website at https://www.fda.gov/news-events/public-health-focus/expanded-access.
Ractigen is not currently making its investigational products available on an expanded access basis anywhere in the world, as we believe that our clinical trials are the most appropriate way to access our investigational products. We encourage patients who are interested in accessing RAG-01 treatment to talk to their physician about participating in a clinical trial. Information about the trial of RAG-01, including enrollment status, eligibility criteria, and locations, is available at https://clinicaltrials.gov/study/NCT06351904.
If we determine that expanded access to RAG-01 becomes appropriate in the future, this website and policy will be updated. If you have further questions, please feel free to contact us at expanded.access@ractigen.com with any questions.
Consistent with the 21st Century Cures Act, Ractigen Therapeutics may revise this policy at any time.
Amyotrophic Lateral Sclerosis (ALS), often known as Lou Gehrig’s disease, is a devastating neurodegenerative disorder that gradually destroys motor neurons in the brain and spinal cord. A subset of this disease, SOD1-ALS, is caused by mutations in the SOD1 gene, which account for about 20% of all familial ALS cases and 1-2% of sporadic ALS cases. These mutations lead to the production of a toxic protein that contributes to the degeneration of motor neurons. The average life expectancy after diagnosis is only 2-5 years, and current treatments can only modestly extend survival or slow the progression. Thus, there remains a significant unmet medical need for more effective therapies.
Ractigen Therapeutics is advancing RAG-17, a pioneering siRNA therapy designed to silence the SOD1 gene and reduce the production of the destructive protein implicated in SOD1-ALS. Unlike traditional drugs, RAG-17 utilizes the power of RNA interference (RNAi) to act at the root cause of the disease. This therapeutic agent utilizes Ractigen’s innovative SCADTM architecture, which links the duplex siRNA to a short oligonucleotide aptamer, facilitating efficient and sustained delivery within the central nervous system (CNS) via intrathecal injection.
Extensive preclinical studies in mouse and rat models of SOD1-ALS have demonstrated the remarkable efficacy of RAG-17. It significantly delayed the onset of ALS symptoms, enhanced motor functions, and extended survival. Remarkably, RAG-17 remained effective even when administered after disease onset, offering hope for patients already experiencing the devastating effects of ALS. These outcomes suggest that RAG-17 could dramatically alter the treatment paradigm for patients with SOD1-ALS, providing them with the prospect of an improved quality of life and extended longevity.
An Investigator Initiated Trial (IIT) assessing RAG-17 in adult ALS patients with an SOD1 mutation has been completed, demonstrating positive safety and preliminary efficacy data. Based on these encouraging results, a Phase I clinical trial is now ongoing in China to further evaluate the safety, tolerability, and pharmacokinetics of RAG-17.
Duan C, Kang M, Liu K, Gan Z, Li G, Chen J, Schacht I, Place RF, Li LC. RAG-17: A Novel siRNA Conjugate Demonstrating Efficacy in Late-Stage Treatment of SOD1G93A ALS mice. bioRxiv. 2023:2023-11. DOI: 10.1101/2023.11.23.568255
Duan C, Kang M, Pan X, Gan Z, Huang V, Li G, Place RF, Li LC. Intrathecal administration of a novel siRNA modality extends survival and improves motor function in the SOD1G93A ALS mouse model. Molecular Therapy-Nucleic Acids. 2024 Mar 12;35(1). DOI: 10.1016/j.omtn.2024.102147. PMID: 38435120; PMCID: PMC10907209.
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