Cartesian Therapeutics(US:RNAC)2022-03-10 13:02ImmTOR Platform and Applications - The ImmTOR platform encapsulates rapamycin in biodegradable nanoparticles, designed to induce antigen-specific immune tolerance[18]. - ImmTOR has demonstrated the ability to inhibit the formation of neutralizing antibodies to adeno-associated virus (AAV) capsids, potentially enabling re-dosing of gene therapies[21]. - ImmTOR is manufactured under current good manufacturing practice (cGMP) requirements, enhancing the scalability of tolerance programs[26]. - ImmTOR has shown potential hepatoprotective effects in preclinical studies, which may allow for multiple lower doses of AAV vectors to mitigate toxicity risks[41]. - The ImmTOR platform is focused on genetic metabolic diseases, with potential applications in lysosomal storage diseases and genetic muscular diseases, and has been licensed to AskBio, Sarepta, and Takeda for specific targets[47]. - ImmTOR-IL has the potential to improve the efficacy and safety profile of biologic therapies beyond ImmTOR alone[21]. - Preclinical studies indicate that ImmTOR can induce antigen-specific T regulatory cells, potentially offering a novel approach to autoimmune disease treatment[91]. - The lead autoimmune disease indication is Primary Biliary Cholangitis (PBC), which has a significant unmet medical need and is targeted by the ImmTOR immune tolerance platform[94]. Clinical Trials and Results - The combination of ImmTOR and pegadricase is currently being evaluated in a Phase 3 clinical trial for chronic refractory gout[21]. - SEL-212, which combines ImmTOR with pegadricase, is in two pivotal Phase 3 studies (DISSOLVE I and DISSOLVE II), with top-line data expected in Q4 2022[58]. - In Phase 1b trials, increasing doses of ImmTOR showed a dose-related reduction in uricase ADAs and an increase in pegadricase half-life, leading to substantial reductions in serum uric acid levels[66]. - In the Phase 2 trial of SEL-212, 66% of patients (21 out of 32) achieved a reduction of SUA to less than 6.0 mg/dL after five monthly doses[67]. - The DISSOLVE clinical program consists of two trials, each expected to enroll up to 120 patients, with a primary endpoint of maintaining SUA levels below 6 mg/dL at six months[75]. - The SEL-399 clinical trial demonstrated that AAV8 empty capsids elicited peak median anti-AAV8 neutralizing antibody titers of 1:6875, with significant reductions to 1:25 and 1:5 in the 0.15 mg/kg and 0.3 mg/kg ImmTOR cohorts, respectively, representing a 50-fold and 250-fold difference compared to control subjects[43]. - At Day 30, 100% of subjects receiving 0.3 mg/kg ImmTOR exhibited NAb titers of 1:25 or less, while 67% of these subjects had titers of 1:5 or less[43]. - In the Phase 2 COMPARE trial, SEL-212 showed a 58% responder rate in patients with tophi at baseline compared to 39% for pegloticase[73]. Strategic Collaborations and Licensing - The company plans to pursue strategic collaborations and licensing transactions to develop proprietary compounds and expand its portfolio[22]. - The company is partnering with Ginkgo Bioworks to design novel enzymes and proteins that can be paired with ImmTOR for treating rare diseases[38]. - The collaboration with IGAN Biosciences includes an exclusive license to develop IgA proteases for IgA-mediated diseases[80]. - The company has entered into multiple strategic licensing agreements, including potential milestone payments of up to $1.124 billion with Takeda Pharmaceuticals for the ImmTOR technology[102]. - The collaboration with Ginkgo Bioworks includes milestone payments of up to $1.1 billion for the development of novel AAV capsids[97]. - The AskBio License Agreement includes upfront fees of $7 million and potential milestone payments of up to $237 million for products targeting Pompe Disease[108]. - The strategic licensing agreement with Genovis includes milestone payments and royalties based on worldwide sales in the low double digits[98]. Financial Overview and Funding - The company incurred net losses of $25.7 million for the year ended December 31, 2021, and $68.9 million and $55.4 million for the years ended December 31, 2020 and 2019, respectively, with an accumulated deficit of $430.3 million as of December 31, 2021[193]. - The company has no source of product revenue and does not expect to generate product revenue for the foreseeable future[193]. - The company expects to incur significant expenses and operating losses for the foreseeable future as it continues to develop its ImmTOR platform and product candidates[194]. - The company anticipates needing substantial additional funding to complete the development of its product candidates and commercialize its products if approved[193]. - The company expects to fund its current planned operations into Q3 2023 with existing cash and cash equivalents, but may need additional funding to continue operations and product development[198]. - Future capital requirements will depend on various factors, including the success of clinical trials and the ability to raise additional funds on favorable terms[199]. - The company has a term loan of up to $35 million, with $25 million funded as Term A Loan and $10 million as Term B Loan, which may restrict operational flexibility[201]. Regulatory Environment and Challenges - The company is subject to significant regulatory scrutiny, particularly regarding the approval of gene therapy products in the U.S. and EU[193]. - Regulatory approval processes for gene therapy candidates are expected to be lengthy and rigorous, potentially delaying commercialization[213]. - The company is facing challenges in the regulatory approval process for its product candidates, which may lead to delays or increased costs[215]. - Regulatory authorities have substantial discretion in the approval process, which may result in the rejection of marketing applications or requests for additional studies[216]. - Changes in regulatory guidelines could significantly impact the timeline and feasibility of bringing products to market[215]. - The FDA aims to review 90% of standard BLAs within 10 months and 90% of priority BLAs within 6 months from the filing date, although it does not always meet these goals[149]. - The FDA requires rigorous post-approval compliance with cGMP regulations, including quality control and reporting of adverse effects[157]. - The ongoing COVID-19 pandemic has impacted business operations and may continue to disrupt clinical trials and preclinical studies[210]. Employee and Operational Insights - The company has a voluntary turnover rate of 12.87% as of 2021, with 66% of its employees holding advanced degrees[185]. - The company pays 100% of an employee's deductible and co-insurance payments to assist with healthcare costs[187]. - The company has invested in employee well-being through competitive compensation and benefits, including equity compensation programs[187]. - The company relies on third parties for the manufacture of its product candidates and for conducting clinical trials, which may not perform satisfactorily[193]. - The company maintains close coordination with regulatory authorities, but this does not guarantee success in the approval process[216]. Market Competition and Risks - The company faces competition from larger pharmaceutical firms and smaller biopharmaceutical companies, which may have greater resources and market presence[129]. - SEL-212 may compete with existing therapies for gout, including pegloticase, which could impact its market potential[132]. - The company is at risk of incurring additional costs or experiencing delays due to potential adverse side effects or immune responses to its product candidates[217]. - Adverse developments in clinical trials of gene therapy products by other companies may influence regulatory bodies to revise approval requirements, negatively affecting the company's prospects[216].