CD61

-- Received Protocol Assistance Feedback from European Medicines Agency on the Phase 2 Study for RLYB212; Company to Proceed Forward with Clinical Trial Application Process in Europe -- -- Phase 2 Dose Confirmation Study for RLYB212 in Pregnant Women at Higher Risk for FNAIT Expected to Initiate in 2H 2024 -- -- $109.9 million Cash, Cash Equivalents and Marketable Securities as of December 31, 2023; Provides Runway into Mid-2026 -- NEW HAVEN, Conn.--(BUSINESS WIRE)-- Rallybio Corporation (Nasdaq: RLYB), a clinical-stage biotechnology company committed to identifying and accelerating the development of life-transforming therapies for patients with severe and rare diseases, today reported financial results for the fourth quarter and full year ended December 31, 2023 and provided an update on recent program and corporate developments. “We are encouraged by the continued progress we made across our portfolio throughout 2023. Following our February 2024 announcement regarding the prioritization of our portfolio and reorganization of our operations, we believe our existing capital will fund our revised operating plan into the middle of mid-2026 and intend to focus our efforts in 2024 on our clinical-stage programs, RLYB212 and RLYB116. We have received feedback from the European Medicines Agency for RLYB212 and are pleased to now move forward with the clinical trial application process in Europe where we will conduct the Phase 2 dose confirmation study for RLYB212 in pregnant women at higher risk for FNAIT. The Phase 2 study remains on track to initiate in the second half of 2024,” said Stephen Uden, M.D., Chief Executive Officer of Rallybio. Dr. Uden continued, “In parallel, the manufacturing work for RLYB116 is ongoing and we are encouraged by the data indicating the potential to achieve improved tolerability at higher doses. We expect to complete this work and provide an update on the development plan for RLYB116 in the second half of 2024. We also remain committed to advancing our preclinical programs to the next milestone and will seek alternative options to advance and or finance these programs with a goal of realizing the value of these programs.” Recent Business Highlights and Upcoming Milestones: Corporate Updates In February 2024, Rallybio announced a prioritization of its portfolio and 45% workforce reduction to focus the Company’s resources on its two Phase 2 ready assets, RLYB212, a novel human monoclonal anti-HPA-1a antibody in development for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT), and RLYB116, a once-weekly, low volume subcutaneously injected inhibitor of complement component 5 (C5) in development for patients with complement mediated diseases. With these changes, Rallybio announced that the Company expects its cash runway to extend into the middle of 2026. The workforce reduction included 19 roles and will be substantially complete by the end of the first quarter of 2024. Rallybio estimates that the workforce reduction will result in aggregate charges of approximately $3.3 million primarily for one-time employee severance and benefit costs, excluding share-based compensation expense. Maternal Fetal Blood Disorders In November 2023, Rallybio announced preliminary data from the completed multiple dose cohort of the Phase 1 safety and pharmacokinetics (PK) study for RLYB212. The Phase 1 multiple dose cohort for RLYB212 was initiated in the first quarter of 2023 to evaluate the safety and PK of subcutaneous (SC) RLYB212 based on repeat dosing over 12 weeks. The preliminary data demonstrated that multiple dose PK were consistent both within and between subjects and, together with the Company’s clinical pharmacology modeling predictions, support a once monthly dosing regimen for the planned Phase 2 study in pregnant women at higher risk for FNAIT. Consistent with previously reported data, RLYB212 was observed to be generally well-tolerated with no reports of injection site reactions or serious adverse events. Rallybio announced today that the Company has received Protocol Assistance Feedback from the European Medicines Agency (EMA) on the RLYB212 Phase 2 study, and the Company is now moving forward with Clinical Trial Applications to support conduct of the Phase 2 study in Europe. Rallybio continues to expect to initiate the Phase 2 dose confirmation study in pregnant women at higher risk for FNAIT in the second half of 2024. The Company continues to screen in the FNAIT natural history alloimmunization study, a non-interventional study designed to provide a contemporary dataset for HPA-1a alloimmunization frequency in a racially and ethnically diverse population. The Company expects screening for the natural history study to continue simultaneously with execution of the Phase 2 dose confirmation study. As of March 1, 2024, Rallybio has screened approximately 9,400 women in the natural history study, and expects to screen between 20,000 and 30,000 women in the study. Complement Dysregulation In December 2023, Rallybio announced preliminary Phase 1 multiple ascending dose data for RLYB116. Results demonstrated that a 100 mg low volume once-a-week dose of subcutaneously administered RLYB116 achieved sustained mean reductions in free C5 of greater than 93%. In addition, RLYB116 administered as a 100 mg once-a-week dose was observed to be generally well tolerated with injection site reaction as the most common adverse event (AE) in the cohort, occurring in 60% of the participants in the cohort. All AEs with the 100 mg weekly dose were mild in severity. While the exposure concentrations of RLYB116 demonstrated in the Phase 1 study are expected to be suitable for the treatment of patients with generalized myasthenia gravis, the Company believes ongoing manufacturing enhancements will enable higher exposure to RLYB116, supporting the treatment of patients with a broader range of complement-mediated diseases, including paroxysmal nocturnal hemoglobinuria and antiphospholipid syndrome. The manufacturing work is progressing and Rallybio is encouraged by the data indicating the potential to achieve improved tolerability at higher doses. Rallybio continues to expect to complete this manufacturing work in the second half of 2024 and to provide an update on the development plan for RLYB116 at that time. Rallybio, together with its partner EyePoint Pharmaceuticals, Inc., continue to evaluate sustained delivery of Rallybio’s inhibitor of C5 using EyePoint’s proprietary technology for sustained intraocular drug delivery. Rallybio and EyePoint expect to provide an update on this collaboration in the first half of 2024. Preclinical Programs The revised operating plan will fund preclinical program activities to important 2024 milestones, as described below. Beyond achievement of these milestones, Rallybio will seek alternative options to further advance these programs, including additional partnerships and other forms of non-dilutive financing. RLYB331, Matriptase-2 (MTP-2) Inhibitor: Completion of the ongoing preclinical activities, with data expected in the first half of 2024. ENPP1 Inhibitor, Exscientia Partnership: Lead AI-designed compounds enter candidate selection process in the second half of 2024. AbCellera Partnership: Advancement of discovery efforts to the next research milestone in the second half of 2024. Fourth Quarter and Full Year 2023 Financial Results Research & Development (R&D) Expenses: R&D expenses were $15.9 million for the fourth quarter of 2023, compared to $10.8 million for the same period in 2022. R&D expenses for the fourth quarter 2023 increased primarily due to an increase in costs to advance RLYB212, RLYB116 and RLYB331 as compared to the prior year. R&D expenses were $53.5 million for the year ended December 31, 2023 compared to $40.7 million for the year ended December 31, 2022. R&D expenses for the year ended December 31, 2023 increased primarily due to an increase in costs to advance RLYB212, RLYB116 and RLYB331 and additional R&D related headcount costs, including share-based compensation expense as compared to the prior year. These costs were offset by a decrease in R&D asset acquisition costs and R&D costs related to RLYB114. General & Administrative (G&A) Expenses: G&A expenses were $5.2 million for the fourth quarter of 2023, compared to $6.3 million for the same period in 2022. G&A expenses for the fourth quarter of 2023 decreased primarily due to a decrease in payroll and personnel-related costs, lower director and officer insurance premiums and lower other general and administrative related expenses as compared to the prior year. G&A expenses were $25.4 million for the year ended December 31, 2023 compared to $27.2 million for the year ended December 31, 2022. The decrease in G&A expenses for the year ended December 31, 2023 was primarily due to a decrease in payroll and personnel-related costs and lower director and officer insurance premiums; offset by increases in other general and administrative related expenses. Net Loss and Net Loss Per Common Share: Net loss was $20.2 million for the fourth quarter of 2023, or net loss per common share of $0.50 compared to a net loss of $16.2 million, or net loss per common share of $0.46 for the fourth quarter of 2022. Net loss was $74.6 million, or net loss per share of $1.84, for the year ended December 31, 2023 compared to $66.7 million, or net loss per share of $2.09, for the year ended December 31, 2022. Cash Position: As of December 31, 2023, cash, cash equivalents, and marketable securities were $109.9 million. About Rallybio Rallybio (Nasdaq: RLYB) is a clinical-stage biotechnology company with a mission to develop and commercialize life-transforming therapies for patients with severe and rare diseases. Rallybio has built a broad pipeline of promising product candidates aimed at addressing diseases with unmet medical need in areas of maternal fetal health, complement dysregulation, hematology, and metabolic disorders. The Company has two clinical stage programs: RLYB212, an anti-HPA-1a antibody for the prevention of fetal and neonatal alloimmune thrombocytopenia (FNAIT) and RLYB116, an inhibitor of complement component 5 (C5), with the potential to treat several diseases of complement dysregulation, as well as additional programs in preclinical development. Rallybio is headquartered in New Haven, Connecticut. For more information, please visit and follow us on LinkedIn and Twitter. Forward-Looking Statements This press release contains forward-looking statements that are based on our management’s beliefs and assumptions and on currently available information. All statements, other than statements of historical facts contained in this press release are forward-looking statements. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements concerning the timing of initiation of the Phase 2 dose confirmation study for RLYB212, the release of screening numbers of women in the natural history study, whether the results of the natural history study and the planned Phase 2 dose confirmation study will be sufficient to support design and implementation of a Phase 3 registrational study for RLYB212, whether the manufacturing work for RLYB116 will be timely completed or successful, our expectations regarding the usefulness of data from our clinical studies, the timing of achieving milestones in 2024 for our preclinical programs, the likelihood that Rallybio will be successful in developing RLYB212, RLYB116, or any of our other product candidates, our ability to successfully identify and implement alternative and acceptable options to further advance our programs, expected costs related to the workforce reduction and related charges, including the timing of such charges, the expected use of operating cost savings associated with the updated operating plan and the timing, our estimates of our capital requirements and the sufficiency thereof, our ability to advance our portfolio, and our cash runway. The forward-looking statements in this press release are only predictions and are based largely on management’s current expectations and projections about future events and financial trends that management believes may affect Rallybio’s business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions, including, but not limited to, our ability to successfully initiate and conduct our planned clinical trials, including the FNAIT natural history study, and the Phase 2 clinical trial for RLYB212, and complete such clinical trial and obtain results on our expected timelines, or at all, whether our cash resources will be sufficient to fund our operating expenses and capital expenditure requirements and whether we will be successful raising additional capital, our ability to identify new product candidates and successfully acquire such product candidates from third parties, our ability to enter into strategic partnerships or other arrangements, including the development of RLYB114, competition from other biotechnology and pharmaceutical companies, and those risks and uncertainties described in Rallybio’s filings with the U.S. Securities and Exchange Commission (SEC), including Rallybio’s Quarterly Report on Form 10-Q for the period ended September 30, 2023, and subsequent filings with the SEC. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Except as required by applicable law, we are not obligated to publicly update or revise any forward-looking statements contained in this press release, whether as a result of any new information, future events, changed circumstances or otherwise. Financial Tables RALLYBIO CORPORATION SELECTED CONDENSED CONSOLIDATED FINANCIAL INFORMATION Condensed Consolidated Statements of Operations and Comprehensive Loss (Unaudited) FOR THE THREE MONTHS ENDED DECEMBER 31, FOR THE YEAR ENDED DECEMBER 31 (in thousands, except share and per share amounts) 2023 2022 2023 2022 Operating expenses: Research and development $ 15,924 $ 10,793 $ 53,544 $ 40,689 General and administrative 5,188 6,298 25,388 27,195 Total operating expenses 21,112 17,091 78,932 67,884 Loss from operations (21,112 ) (17,091 ) (78,932 ) (67,884 ) Other income: Interest income 1,448 1,071 6,147 1,963 Other income 35 31 262 342 Total other income, net 1,483 1,102 6,409 2,305 Loss before equity in losses of joint venture (19,629 ) (15,989 ) (72,523 ) (65,579 ) Loss on investment in joint venture 613 214 2,041 1,075 Net loss $ (20,242 ) $ (16,203 ) $ (74,564 ) $ (66,654 ) Net loss per common share, basic and diluted $ (0.50 ) $ (0.46 ) $ (1.84 ) $ (2.09 ) Weighted-average common shares outstanding, basic and diluted 40,639,567 35,516,630 40,447,388 31,821,311 Other comprehensive gain (loss): Net unrealized gain (loss) on marketable securities 223 220 229 (214 ) Other comprehensive gain (loss) 223 220 229 (214 ) Comprehensive loss $ (20,019 ) $ (15,983 ) $ (74,335 ) $ (66,868 ) Condensed Consolidated Balance Sheets (Unaudited) (in thousands) DECEMBER 31, 2023 DECEMBER 31, 2022 Cash, cash equivalents and marketable securities $ 109,929 $ 168,994 Total assets 115,620 180,435 Total liabilities 9,436 11,118 Total stockholders' equity 106,184 169,317

该研究成功制备了一种具有抗血小板药物药效逆转功能的血小板仿生纳米海绵PLT-PFC，其表面保留了大部分血小板膜表面的药物靶点，可以竞争性结合抗血小板药物，有效逆转抗血小板药物的药效。 血栓性疾病严重威胁人类的生命健康，其发病率高居各种疾病之首，主要包括心肌梗塞、缺血性脑卒中、肺栓塞等。随着人们生活水平的不断提高，血栓性疾病的发病率呈上升趋势。 抗血小板药物是多种血栓性疾病长期防治的临床指南推荐一线药物，主要包括环氧合酶-1抑制剂、磷酸二酯酶抑制剂、二磷酸腺苷受体抑制剂、糖蛋白GPIIb/IIIa抑制剂、凝血酶受体抑制剂等。与抗凝治疗相似，长期的抗血小板药物治疗势必会给病人带来严重的出血风险，如皮下出血、消化道出血、颅内出血等，引起致死或致残等严重后果。此外，长期使用抗凝药物/抗血小板药物的病人遭遇车祸或者需要进行紧急手术时，对其体内的抗凝药物/抗血小板药物进行功能逆转可以为病人争取更多的安全治疗时间。 针对抗凝药物，临床上已经具有多种逆转剂可供选择，例如鱼精蛋白、Idarucizumab、Andexanet α、Ciraparantag、重组活化凝血因子VIIa、维生素K等。而抗血小板药物目前尚无已上市逆转剂，只有针对抗血小板药物替格瑞洛的一种单克隆抗体Bentracimab处于临床三期。临床常用的血小板输注策略，在多种抗血小板药物逆转方面效果不佳，并且血小板输注的数量需要严格限制以免带来额外的血栓风险。 2023年1月10日，国家纳米科学中心聂广军研究员团队和中国科学院大学纳米学院张银龙副教授团队合作在 Circulation Research 期刊发表了题为：Platelet-mimicking nanosponges for functional reversal of antiplatelet agents 的研究论文。 该工作针对长期服用抗血小板药物带来的出血风险，以及长期服用抗血小板药物的病人需要紧急介入手术等临床实际科学问题，提出了利用血小板膜纳米海绵对抗血小板药物特异性逆转的策略。与血小板输注不同，纳米海绵惰性内核无主动的血栓块收缩能力，因此在高剂量下无明显的体内致栓风险。 为了证明血小板膜纳米海绵制备过程中，血小板膜表面受体没有丢失，研究者首先通过纳米流式证明了纳米海绵表面P2Y12和αIIb/β3受体的保留。通过SDS-PAGE实验对血小板膜纳米囊泡和纳米海绵的全蛋白进行对比，发现纳米海绵保留了血小板膜的大部分蛋白。进一步地，通过蛋白质组学和免疫印迹分析，同样证明了纳米海绵保留了大部分血小板膜蛋白及重要的受体蛋白（CD41、CD61、P2Y12）。纳米海绵中没有发现管家蛋白GAPDH的存在，证实制备过程中，成功去除血小板内容物蛋白，保证所制备的血小板膜纳米海绵不具有诱导血栓形成的风险。 为了证明纳米海绵PLT-PFC对抗血小板药物具有高的亲和力，研究者通过等温滴定量热法和微量热泳分析等技术手段，分别测定了两者的Ka值和Kd值，实验结果表明，纳米海绵与替格瑞洛（Ticagrelor）、替罗非班（Tirofiban）两种抗血小板药物具有高的亲和系数和低的解离系数，为抗血小板药物的高效逆转提供了理论基础。研究者通过体外血小板聚集实验证明了纳米海绵PLT-PFC可以有效逆转Ticagrelor的抗血小板活性。 随后，研究者在小鼠体内评价纳米海绵PLT-PFC对Ticagrelor的功能逆转效应。通过尾静脉注射的方式提前给药Ticagrelor，随后注射纳米海绵PLT-PFC。通过高效液相色谱测定给药后不同时间点血液中Ticagrelor的浓度，并通过尾尖出血实验评价小鼠的止血功能。实验结果表明，PLT-PFC可以有效降低Ticagrelor曲线下面积，并恢复小鼠的止血功能。 最后，研究者评价了纳米海绵PLT-PFC在抗血小板药物引起的卒中出血转化模型中的作用。实验性脑卒中模型小鼠在造模之前连续三天给药Ticagrelor，造模前注射纳米海绵PLT-PFC，造模完成后给予溶栓治疗，通过核磁共振成像技术和Evans blue染料渗透实验评价小鼠脑出血和坏死面积。实验结果表明，抗血小板治疗可以增加卒中溶栓治疗的出血风险和脑梗死面积，而PLT-PFC可以有效逆转抗血小板药物的药效，降低出血风险，预防抗血小板药物诱导的脑栓塞面积增加。 综上所述，该研究成功制备了一种具有抗血小板药物药效逆转功能的血小板仿生纳米海绵PLT-PFC，其表面保留了大部分血小板膜表面的药物靶点，可以竞争性结合抗血小板药物，有效逆转抗血小板药物的药效。与血小板输注相比，惰性内核的引入可以有效降低血栓风险。PLT-PFC对抗血小板药物的功能逆转在尾尖出血模型及卒中出血转化模型中都得到了验证。该研究提出了一种广谱的抗血小板药物逆转策略，为临床抗血小板药物的功能逆转提供新思路。