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Rallybio(RLYB) - 2023 Q4 - Annual Report
RLYBRallybio(RLYB)2024-03-12 20:26

Drug Development and Clinical Trials - The company has developed RLYB212 for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT), with over 22,000 high-risk pregnancies estimated annually in the U.S., Canada, the UK, and Australia[28]. - RLYB212 has completed two Phase 1 clinical trials, with preliminary results indicating a well-tolerated profile and a potential once-monthly dosing regimen for the upcoming Phase 2 trial[29]. - The Phase 1b trial of RLYB212 demonstrated a dose-dependent reduction in mean platelet elimination half-life, achieving a reduction of 90% or more in HPA-1a positive platelets[30]. - The company plans to initiate a Phase 2 clinical trial for RLYB212 in the second half of 2024, following the completion of Phase 1 trials[29]. - The FNAIT natural history study aims to screen up to 30,000 expectant mothers to gather data for future clinical trials, with approximately 9,400 women screened as of March 1, 2024[31]. - RLYB116, an inhibitor of complement component 5 (C5), has shown over 99% reduction in free C5 within 24 hours of a single 100 mg subcutaneous injection in Phase 1 trials[34]. - The multiple ascending dose (MAD) portion of the RLYB116 trial indicated sustained mean reductions in free C5 of greater than 93% after a once-weekly 100 mg dose[36]. - RLYB331, a preclinical monoclonal antibody targeting Matriptase-2, aims to address severe anemia and iron overload, with data expected in the first half of 2024[38]. - The company plans to initiate a Phase 2 trial of RLYB212 in expectant mothers at higher FNAIT risk in the second half of 2024, focusing on PK and safety assessments[72]. - The Phase 1 clinical trial for RLYB116 included a single-blind, placebo-controlled design with doses ranging from 2mg to 300mg, enrolling 8 subjects per cohort[90]. Market Opportunities and Collaborations - The market opportunity for RLYB212 is estimated to exceed 1billion,targetingapproximately22,000high−riskpregnanciesannuallyintheU.S.,Canada,theUK,andmajorEuropeancountries[53][54].−Approximately21 billion, targeting approximately 22,000 high-risk pregnancies annually in the U.S., Canada, the UK, and major European countries[53][54]. - Approximately 2% of the Caucasian population is HPA-1a negative, leading to an estimated 110,000 HPA-1a negative expectant mothers annually in the targeted regions[54]. - The collaboration with AbCellera aims to co-develop up to five rare disease therapeutic targets, enhancing Rallybio's product pipeline[42][43]. - The joint venture is developing a small molecule ENPP1 inhibitor for the treatment of Hypophosphatasia (HPP), a rare genetic disease with an incidence of 1 in 100,000 to 1 in 300,000 in the U.S. and Canada for severe cases[40]. - The partnership with Exscientia is focused on discovering small molecules for rare metabolic diseases, initially targeting ENPP1 for treating hypophosphatasia (HPP)[103][104]. Intellectual Property and Regulatory Compliance - As of March 1, 2024, the company owns two patent families related to its FNAIT prevention program, with patents expiring in 2035 and 2026, and one U.S. patent expiring in November 2030 due to a PTA granted by the USPTO[130]. - The company has a multi-layered approach to securing intellectual property rights, including acquiring rights through purchase or exclusive license and filing patent applications[123]. - The company is managing prosecution of a patent family relating to RLYB331 and has pending applications in over 20 countries, including the U.S. and China[133]. - The company intends to pursue relevant marketing exclusivities in the U.S. and foreign countries for its candidate products, although there is no certainty that such exclusivities will be granted[128]. - The company has confidence in its protective measures for trade secrets, but acknowledges that breaches can occur and remedies may be inadequate[129]. - The FDA application fee for an NDA or BLA in fiscal year 2024 is approximately 4.0 million, with an annual program fee exceeding 415,000perprogram[185].−TheFDAmayissueaCompleteResponseLetter(CRL)iftheapplicationdoesnotmeetregulatorycriteria,outliningdeficienciesthatmustbeaddressedforreconsideration[192].−TheFDAmayimposepost−approvalrequirements,includingPhase4clinicaltrialstofurtherassesssafety[193].−TheFDAmaydesignatecertainproductsforexpediteddevelopmentiftheyaddressunmetmedicalneedsinseriousconditions[198].ManufacturingandDevelopmentStrategy−ThecompanyisprioritizingenhancementstothemanufacturingprocessofRLYB116,expectedtobecompletedinthesecondhalfof2024,toimprovetolerabilityandexpandtreatmentoptions[36].−Thecompanycurrentlyreliesonthird−partycontractmanufacturersforthemanufactureofproductcandidatesforpreclinicalandclinicaltesting[163].−Thecompanyexpectstocontinuedevelopingproductcandidatesthatcanbeproducedcost−effectivelyatcontractmanufacturingfacilities[167].−Thecompanyisconsideringpartnershipsornon−dilutivefinancingtosupportfutureclinicaldevelopmentofRLYB116[76].−ThecompanyhasacquiredrightstocertainC5inhibitorcompoundsfromSobi,withanupfrontpaymentof415,000 per program[185]. - The FDA may issue a Complete Response Letter (CRL) if the application does not meet regulatory criteria, outlining deficiencies that must be addressed for reconsideration[192]. - The FDA may impose post-approval requirements, including Phase 4 clinical trials to further assess safety[193]. - The FDA may designate certain products for expedited development if they address unmet medical needs in serious conditions[198]. Manufacturing and Development Strategy - The company is prioritizing enhancements to the manufacturing process of RLYB116, expected to be completed in the second half of 2024, to improve tolerability and expand treatment options[36]. - The company currently relies on third-party contract manufacturers for the manufacture of product candidates for preclinical and clinical testing[163]. - The company expects to continue developing product candidates that can be produced cost-effectively at contract manufacturing facilities[167]. - The company is considering partnerships or non-dilutive financing to support future clinical development of RLYB116[76]. - The company has acquired rights to certain C5 inhibitor compounds from Sobi, with an upfront payment of 5.0 million and potential milestone payments totaling up to $116.0 million[145]. Safety and Efficacy Data - RLYB212 demonstrated a dose-dependent, rapid, and complete elimination of transfused HPA-1a positive platelets, achieving a ≥90% reduction in mean platelet elimination half-life, with mean values of 5.8 hours (0.09mg dose) and 1.5 hours (0.29mg dose) compared to 71.7 hours for placebo[70]. - RLYB116 demonstrated a reduction in free C5 greater than 99% within 24 hours after a single 100 mg dose, with sustained mean reductions of over 93% at day 29[92][95]. - The mean elimination half-life of RLYB116 was greater than 300 hours, indicating low inter-subject variability and consistent increases in exposure relative to dose[92][96]. - The MAD portion of the Phase 1 trial included four dosing cohorts, with mild to moderate adverse events reported, primarily gastrointestinal in nature[93][96]. - RLYB116 aims to provide a more accessible treatment option for patients with gMG, addressing significant unmet needs in the market[82].