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Item 1. Business

2025-03-13 compared with 2024-03-12 · 367 added, 376 removed, 784 unchanged (49% of the section changed)

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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.

Both programs have completed Phase 1 clinical trials, and we currently plan to initiate a Phase 2 clinical trial of RLYB212 in the second half of 2024.

RLYB212 is currently in a Phase 2 clinical trial in pregnant women, and we plan to initiate a confirmatory pharmacokinetics (“PK”) and pharmacodynamics ("PD") study of RLYB116 in the second quarter of 2025.

At Rallybio Corporation (“Rallybio” or the "Company"), we do not accept that millions of patients suffering from devastating rare diseases should have to live without transformative treatments.

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In addition, our ability to source these product candidates is facilitated by our extensive network of relationships with leaders in industry and in academic centers worldwide.

Our Chief Executive Officer, Stephen Uden, M.D., and Executive Chairman, Martin W.

Our Chief Executive Officer, Stephen Uden, M.D., and Chairman, Martin W.

Mackay, Ph.D., previously worked together in different organizations to successfully build, develop, and launch transformative therapies for patients with rare diseases.

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Albumin-binding domain;

Hypophosphatasia;

Ectonucleotide pyrophosphatase/phosphodiesterase 1

*Disease areas under consideration:

hematology, including disorders such as PNH and antiphospholipid syndrome;

and neurology, including disorders such as gMG

** Rallybio and EyePoint Pharmaceuticals are conducting an evaluation to assess the viability of using EyePoint's delivery technology with Rallybio's complement inhibitor;

following the evaluation, the parties will determine whether to advance the collaboration, in which case EyePoint would assume development rights

Prevention of FNAIT

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Based on the data generated to date and the clinical precedent for effective prevention of maternal alloimmunization by anti-RhD prophylaxis, which has resulted in the virtual elimination of Rhesus disease, we believe that targeting HPA-1a with an anti-HPA-1a antibody has the potential to drive rapid elimination of HPA-1a positive platelets from the circulation of expectant mothers, prevent alloimmunization and thereby prevent the occurrence of FNAIT.

We have completed two RLYB212 clinical trials:

We are currently conducting a Phase 2 clinical trial of RLYB212 in pregnant women at higher risk for HPA-1a alloimmunization and FNAIT at sites across Europe.

The primary objective of this single-arm Phase 2 trial is to assess the PK and safety of RLYB212 with secondary objectives that include assessments of pregnancy and neonatal/infant outcomes, and the occurrence of emergent HPA-1a alloimmunization.

Subcutaneous ("SC") administration of RLYB212 will be initiated by Gestational Week 16 and will continue every four weeks through parturition.

The Phase 2 trial is designed to enroll participants in three stages:

first with a sentinel pregnant woman, an initial cohort ("Cohort 1") that will include three pregnant women, and a second cohort ("Cohort 2") that will include four pregnant women, for a total target enrollment of eight participants.

A data review for participants and infants is planned prior to the initiation of each cohort.

The Phase 2 trial follows completion of two RLYB212 clinical trials:

a Phase 1 first-in-human clinical trial and a Phase 1b proof-of-concept clinical trial.

The Phase 1 first-in-human clinical trial was a single-blind, placebo-controlled study that investigated the safety and pharmacokinetics (“PK”) of subcutaneous (“SC”) administration of RLYB212 in HPA-1a negative healthy participants.

The Phase 1 first-in-human clinical trial was a single-blind, placebo-controlled study that investigated the safety and PK of SC administration of RLYB212 in HPA-1a negative healthy participants.

The clinical trial included a single dose cohort and a multiple dose cohort.

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We reported preliminary results from the multi-dose cohort in the fourth quarter of 2023.

The data and our clinical pharmacology modeling predictions support a once monthly dosing regimen for the planned Phase 2 clinical trial.

The data and our clinical pharmacology modeling predictions support a once monthly dosing regimen for the Phase 2 clinical trial.

RLYB212 was observed to be generally well-tolerated with no reports of injection site reactions or serious adverse events.

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The study included 11 males aged 18 to 65 years, randomized to RLYB212 0.09mg (n=4), RLYB212 0.29mg (n=5), or placebo (n=2).

We reported the results from this trial at the 31st Congress of the International Society on Thrombosis and Haemostasis ("ISTH") in the second quarter of 2023.

We reported top-line results from this trial at the 31st Congress of the International Society on Thrombosis and Haemostasis ("ISTH") in the second quarter of 2023 and announced publication of the complete dataset in Thrombosis and Haemostasis in the third quarter of 2024.

The results showed that SC RLYB212 administration produced a dose-dependent, rapid, and complete elimination of transfused HPA-1a positive platelets in HPA-1a negative subjects, with both doses meeting the prespecified proof-of-concept criteria of ≥90% reduction in mean platelet elimination half-life.

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Additionally, we are conducting a FNAIT Natural History Alloimmunization Study ("FNAIT natural history study").

This prospective, non-interventional, multinational natural history study is designed to screen up to 30,000 expectant mothers presenting at gestational week 10 to 14 prenatal visit to determine the frequency of women at higher FNAIT risk among expectant mothers of different racial and ethnic characteristics, as well as the frequency of HPA-1a alloimmunization and pregnancy outcomes among these women.

This prospective, non-interventional, multinational natural history study is designed to screen expectant mothers presenting at gestational week 10 to 14 prenatal visit to determine the frequency of women at higher FNAIT risk among expectant mothers of different racial and ethnic characteristics, as well as the frequency of HPA-1a alloimmunization and pregnancy outcomes among these women.

Subject to future discussions with regulatory authorities, we expect that data from this study will contribute to a control dataset for a future single-arm Phase 3 registrational clinical trial for RLYB212.

An additional objective of the FNAIT natural history study is to operationalize de novo the laboratory screening test paradigm for FNAIT risk and generate FNAIT laboratory test performance data that we plan to use for future regulatory discussions.

As of March 1, 2024, approximately 9,400 women have been screened as part of the study.

As of January 31, 2025, more than 14,300 women have been screened as part of the study.

Treatment of Disorders Due to Complement Dysregulation

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Our most advanced product candidate in this therapeutic area is RLYB116, an inhibitor of C5, which is a central component of the terminal complement pathway.

RLYB116 is an Affibody molecule attached to an albumin binding domain that has the potential to drive the rapid, complete, and sustained inhibition of C5 with a SC injection.

RLYB116 is an Affibody molecule attached to an albumin binding domain ("ABD") that has the potential to drive the rapid, complete, and sustained inhibition of C5 with a SC injection.

We have completed a Phase 1 clinical trial in healthy participants that included the study of RLYB116 as both a single ascending dose (“SAD”) and a multiple ascending dose (“MAD”).

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The terminal elimination half-life of RLYB116 was greater than 300 hours.

The MAD portion of the RLYB116 Phase 1 trial included an adaptive single-blind design with a four-week treatment duration to evaluate the safety, tolerability, PK, and pharmacodynamics ("PD") of RLYB116 with multiple dose SC administration.

The MAD portion of the RLYB116 Phase 1 trial included an adaptive single-blind design with a four-week treatment duration to evaluate the safety, tolerability, PK, and PD of RLYB116 with multiple dose SC administration.

The MAD portion of the trial included four cohorts:

Cohort 1 (weekly dosing of 100 mg), Cohort 2 (3 doses of 100 mg the first week followed by weekly dosing), Cohort 3 (150 mg weekly dosing reduced to 125 mg weekly dosing) and Cohort 4 (75 mg twice the first week followed by 100 mg twice per week) with post-treatment for 10 weeks.

Cohort 1 (weekly dosing of 100 mg), Cohort 2 (3 doses of 100 mg the first week followed by weekly dosing), Cohort 3 (150 mg weekly dosing reduced to 125 mg weekly dosing) and

Cohort 4 (75 mg twice the first week followed by 100 mg twice per week) with post-treatment for 10 weeks.

In December 2023, we reported data from the MAD portion of the trial that demonstrated a 100 mg low volume (1 mL) once-weekly dose of subcutaneously administered RLYB116 achieved sustained mean reductions in free C5 of greater than 93%, including at Day 29 with measurement prior to the last dose.

The reduction from pre-treatment free C5 at 24 hours after the first dose of 100 mg was greater than 99%.

In the MAD portion of the Phase 1 trial, RLYB116 demonstrated low inter-subject variability and consistent increases in exposure relative to dose with a mean estimated elimination half-life for RLYB116 of

RLYB116 administered in the MAD trial as a 100 mg once-weekly dose was also observed to be generally well tolerated.

Based on data from the MAD portion of the Phase 1 trial and additional work we have conducted with RLYB116, we believe that RLYB116 has the potential to be an effective treatment for patients with certain complement-mediated diseases, including gMG.

We have prioritized enhancements to the manufacturing process that are intended to improve tolerability at higher doses with a low injection volume and infrequent SC administration, thereby opening up the opportunity to treat a wider range of complement-mediated diseases in addition to gMG, including PNH and antiphospholipid syndrome.

We expect the manufacturing work to be completed in the second half of 2024.

Our second C5 inhibitor, RLYB114, is a pegylated C5-targeted Affibody molecule with PK properties designed for the treatment of complement-mediated ophthalmic diseases.

In February 2023 we entered into a collaboration with EyePoint Pharmaceuticals, Inc.

(“EyePoint”) and are using EyePoint’s proprietary technology for sustained intraocular drug delivery, with the initial focus on geographic atrophy, an advanced form of age-related macular degeneration that leads to irreversible vision loss.

Rallybio and EyePoint expect to provide an update on this collaboration in the first half of 2024.

Based on the results of the RLYB116 Phase 1 trial, we conducted a series of biomarker characterization analyses.

These analyses indicate the RLYB116 assay used to measure free C5 in the Phase 1 trial overestimated the levels of free C5 by approximately ten-fold, indicating that RLYB116 produced greater complement inhibition than initially reported.

We now believe that RLYB116 has the potential to be an effective treatment for patients with a variety of complement-mediated diseases, including PNH, gMG and antiphospholipid syndrome ("APS").

We also completed manufacturing process enhancements with a goal of further improving the tolerability of RLYB116.

Based on the results of enhanced analytical techniques, including mass spectrometry, these process enhancements have successfully further purified the RLYB116 drug substance.

As a result, we believe that RLYB116 will have a favorable tolerability profile at doses at and above those evaluated in the Phase 1 MAD trial.

We plan to initiate a RLYB116 confirmatory clinical PK/PD trial in the second quarter of 2025 to demonstrate improved tolerability as well as complete and sustained complement inhibition.

This single-blind MAD trial will evaluate a 4-week treatment duration that will include two cohorts of eight participants each.

Our current plan is that Cohort 1 will evaluate weekly dosing of 150 mg and Cohort 2 will evaluate weekly dosing of 225 mg with 10 weeks of follow-up after the conclusion of treatment.

Hematological Disorders

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The inhibition of MTP-2 significantly increases levels of hepcidin, decreases iron load and treats ineffective erythropoiesis.

In 2024, we re-engineered RLYB331 to extend its half-life.

In the fourth quarter of 2024 we presented preclinical data at the annual meeting of the American Society of Hematology ("ASH") for RLYB332, the long-acting version of RLYB331, including favorable PD data, that support RLYB332 as a long-acting, potentially best-in-class therapy for the treatment of diseases of iron overload.

We believe RLYB332 has the potential to address a significant unmet need for patients with severe anemia with ineffective red blood cell production or erythropoiesis and iron overload, such as polycythemia vera, beta thalassemia and a subset of myelodysplastic syndromes ("MDS"), amongst others.

Currently these patients are underserved by the existing standard of care.

We are continuing with preclinical activities to support the transition of RLYB331 into clinical development and expect to report data from this program in the first half of 2024.

Artificial Intelligence Drug Discovery Collaboration

In July 2019, we formed a joint venture with Exscientia Limited ("Exscientia"), an Oxford, UK-based artificial intelligence ("AI") and machine learning drug discovery company with a proprietary chemical design platform to discover novel small molecule drug candidates.

Our joint venture is focused on the discovery and development of small molecule therapeutics for the treatment of patients with rare metabolic diseases.

The joint venture is currently developing a small molecule targeting an Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 ("ENPP1") inhibitor for the treatment of HPP.

Exscientia was acquired by Recursion Pharmaceuticals, Inc.

("Recursion") in 2024 and we have continued work with Recursion on the discovery of a small molecule targeting an Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 ("ENPP1") inhibitor for the treatment of HPP.

HPP is a rare, genetic disease characterized by mutations in the ALPL gene.

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We believe that a small molecule inhibitor of ENPP1 has the potential to bring meaningful benefit to HPP patients by reducing excess levels of pyrophosphate, thereby removing an inhibitor of calcium mineralization and bone formation.

We and Exscientia continue to work toward the selection of a small molecule development candidate to advance into the clinic targeting ENPP1 for the treatment of patients with HPP.

Proof of mechanism studies are in progress with a leading global HPP expert.

We plan to provide an update on the progress of the program in the second half of 2024.

In 2024 we presented data at the American Society for Bone and Mineral Research ("ASBMR") from an early lead ENPP1 inhibitor, REV101, in a mouse model of later-onset HPP demonstrating a 30% reduction in PPi, a key biomarker that is elevated in HPP and contributes to poor bone mineralization.

Together with Recursion, we also advanced REV102, an ENPP1 inhibitor for the treatment of patients with HPP to position the molecule for additional preclinical development activities in 2025.

AbCellera Collaboration

In December 2022, we entered into a strategic alliance to discover, develop, and commercialize novel antibody-based therapeutics for rare diseases.

This multi-year, multi-target collaboration will combine AbCellera Biologic's ("AbCellera") antibody discovery engine with Rallybio’s clinical and commercial expertise in rare diseases to identify optimal clinical candidates with a goal of delivering therapies to patients.

AbCellera and Rallybio will co-develop up to five rare disease therapeutic targets, which will be chosen together by both companies.

The collaboration will allow Rallybio to add product candidates to our existing pipeline with the option for AbCellera to conduct process development and clinical manufacturing activities.

The first program is focused on addressing the significant unmet therapeutic needs of patients with rare metabolic diseases.

This multi-year, multi-target collaboration will combine AbCellera Biologic's

("AbCellera") antibody discovery engine with Rallybio’s clinical and commercial expertise in rare diseases to identify optimal clinical candidates with a goal of delivering therapies to patients.

We and AbCellera intended that the collaboration would co-develop up to five rare disease therapeutic targets, which will be chosen together by both companies with the first program focused on addressing the significant unmet therapeutic needs of patients with rare metabolic diseases.

Our mission is aligned with our expertise:

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There is currently no approved therapy for the prevention of FNAIT.

Women at higher risk of FNAIT may experience potentially devastating outcomes and we believe there is a significant unmet need for patients.

We believe the clinical data generated to date support continued investment and development of RLYB212 and provide us with an opportunity to deliver a substantially impactful therapeutic in maternal fetal health for expectant mothers with FNAIT.

Furthermore, we estimate that the market opportunity exceeds $1 billion.

We plan to initiate a Phase 2 study in expectant mothers at higher risk of FNAIT in the second half of 2024.

Women at higher risk of FNAIT may experience potentially devastating outcomes and we believe there is a significant unmet need for these patients.

We believe the clinical and non-clinical data generated to date indicate that RLYB212 may prevent FNAIT in pregnant women at higher risk for HPA-1a alloimmunization and were supportive of initiating the ongoing Phase 2 clinical trial in pregnant women.

We enrolled the sentinel woman in February 2025 and expect to report PK and safety data from the second trimester in the second quarter of 2025 and PK and safety data at the time of delivery in the third quarter of 2025 at which time we will determine the next steps for the program including seeking a partner to continue development.

We estimate that the market opportunity for RLYB212 exceeds $1.6 billion.

• Advance RLYB116 for the treatment of diseases of complement dysregulation through partnering or other forms of non-dilutive financing.

In the fourth quarter of 2023, we announced preliminary data from a MAD Phase 1 trial of RLYB116.

Based on the data from this trial, we believe that RLYB116 has the potential to be an effective treatment for patients with certain complement-mediated diseases, including gMG.

We are currently implementing additional manufacturing process improvements that we believe will enable RLYB116 to treat a broader range of complement-mediated diseases.

Given our desire to conserve capital, we will seek to move this program forward with a partner or non-dilutive financing.

• Leverage the progress made to date and maximize the value from our preclinical candidates, including the programs in our collaborations with Exscientia and AbCellera.

Based on the biomarker characterization analyses and manufacturing process enhancements we completed in 2024, we intend to initiate a confirmatory clinical PK/PD trial in the second quarter of 2025.

We will evaluate future development plans for RLYB116 based on the results of this trial but based on the data generated to date, we believe that RLYB116 has the potential to be an effective treatment for patients with a variety of complement-mediated diseases, including PNH, gMG and APS.

• Leverage the progress made to date and maximize the value from our preclinical candidates.

We believe that our preclinical pipeline programs have significant potential to generate value by meeting the unmet needs of patients and we intend to continue to move these forward in a capital-efficient manner.

For example, we are currently conducting preclinical work for RLYB331 and expect to report the results of this work in the first half of 2024 prior to initiating any further development work.

In addition, we are continuing to support our collaborations with Exscientia and AbCellera with a goal of generating additional data from these programs that can inform the most appropriate next steps in development.

As we are able to generate additional data, we will make decisions on the most appropriate next steps in development for each of our preclinical programs.

• Create value from our pipeline through targeted business development activities.

We believe we have assembled a valuable portfolio of product candidates targeting several rare diseases and will seek to unlock that value by leveraging our current and potential future partnerships and collaborations for one or more of these programs.

We believe this will enable us to advance these programs while focusing our development efforts and related spend on RLYB212.

We may also periodically evaluate the potential in-license or acquisition of new programs subject to market conditions and our cash runway.

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RLYB212 is a subcutaneously administered monoclonal anti-HPA-1a antibody for the prevention of FNAIT, a maternal fetal blood disorder that can cause potentially devastating outcomes in the fetus or neonate including miscarriage, neonatal death, and severe life-long neurological disability in the babies that survive.

We have completed two Phase 1 clinical trials for RLYB212 and we intend to initiate the Phase 2 clinical trial for RLYB212 in the second half of 2024.

We have completed two Phase 1 clinical trials for RLYB212 and are currently running a Phase 2 clinical trial in pregnant women at higher risk for HPA-1a alloimmunization and FNAIT.

Based on the preclinical and clinical data to date and our understanding of FNAIT, we believe RLYB212 has the potential to prevent maternal alloimmunization and thereby the occurrence of FNAIT.

We are also currently conducting an FNAIT natural history study.

We are also conducting an FNAIT natural history study.

This prospective, non-interventional, multinational study is designed to determine the frequency of women at higher FNAIT risk among expectant mothers of different racial and ethnic characteristics, as well as the frequency of HPA-1a alloimmunization and pregnancy outcomes among these women.

We expect that data from this study will contribute historical control data to support a planned single-arm Phase 3 registrational clinical trial of RLYB212.

We recently transitioned screening activities from the natural history study to the Phase 2 clinical trial where sites will continue to collect natural history data in women who do not receive RLYB212.

We expect that natural history data from both the natural history study and the Phase 2 clinical trial will contribute historical control data to support a planned single-arm Phase 3 registrational clinical trial of RLYB212.

Maternal fetal blood disorders

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In severe cases, babies may suffer life-long neurological disability or may not survive.

Based on published data, we believe that there are at least 22,000 pregnancies annually that are at high risk of FNAIT in the United States, Canada, the UK, other major European countries, and Australia.

These pregnancies represent expectant mothers who are HPA-1a negative, who are at high risk of alloimmunization and who are carrying an HPA-1a positive fetus.

Studies show that approximately 2% of the Caucasian population is HPA-1a negative.

Based on this frequency and live birth rates of Caucasian women from 2018, we estimate that there are approximately 110,000 HPA-1a negative expectant mothers in the aforementioned countries each year.

From this population of expectant mothers, a subset is at higher risk of FNAIT due to the presence of a specific HLA allele, known as DRB3*01:01.

Based on previously published data and a 2024 epidemiological analysis that we sponsored, we believe that more than 30,000 pregnancies each year in the United States, Canada, the UK, other major European countries, and Australia are at higher risk for FNAIT and could potentially benefit from administration of a monoclonal anti-HPA-1a antibody such as RLYB212.

These pregnancies represent expectant mothers who are HPA-1a negative, who are carrying an HPA-1a positive fetus and who are at high risk of alloimmunization due to the presence of a specific HLA allele, known as DRB3*01:01.

Genetic studies have found that expectant mothers who have this specific HLA allele are approximately 25 times more likely to develop antibodies to HPA-1a than those without this allele.

This higher-risk population represents approximately 27% of HPA-1a negative expectant mothers, or approximately 30,000 individuals.

From this higher-risk population, an estimated 89% of women would not already have antibodies to HPA-1a and, of these, an estimated 86% would be expected to be carrying an HPA-1a positive fetus.

We believe this portion of the higher-risk population could potentially benefit from administration of a monoclonal anti-HPA-1a antibody such as RLYB212.

Pregnancies At High Risk of FNAIT Each Year

NCHS National Vital Statistics Report Volume 68, Number 13, November 30, 2019, Births:

Final Data for 2018;

World Bank Population Data (2018);

Kjeldsen-Kragh, et al Blood 2007;

Hardy-Weinberg estimate;

Kjeldsen-Kragh et al Blood 110, 833-839 (2007)

Given the well-established prevalence of HPA-1a negativity in the Caucasian population, our current estimates of the FNAIT at-risk population are derived from the estimated proportion of Caucasian births from approximately eight million live births per year in the above-mentioned countries.

We are committed, however, to ensuring that all expectant mothers of any race or ethnicity who are at high risk of FNAIT are identified and eligible for treatment.

To this end, we are conducting a FNAIT natural history study, in part to obtain more precise prevalence estimates of the FNAIT at-risk population in racial and ethnic groups that may have been underrepresented in previously published studies.

We believe that data from this study will more precisely inform the size of the FNAIT at-risk population.

We believe that screening for FNAIT risk can be performed routinely and cost effectively as part of standard prenatal testing provided to expectant mothers during pregnancy.

Testing for maternal HPA-1 type and presence of the HLA-DRB3*01:01 allele could occur during the first trimester, and at the same time as other routine blood work and risk screening.

Testing for maternal HPA-1 type and presence of the HLA-DRB3*01:01 allele could occur during the first trimester at the same time as other routine blood work and risk screening.

We don’t expect that an additional blood draw would be required.

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For example, screening and treatment in Rh disease have been highly effective in reducing the number of affected births.

In developed countries with access to prenatal testing and treatment, the prevalence of Rh disease is 2.5 per 100,000 compared to 276 per 100,000 worldwide.

In developed countries with access to prenatal testing and treatment, the prevalence

of Rh disease is 2.5 per 100,000 compared to 276 per 100,000 worldwide.

We believe that applying a similar approach to the prevention of FNAIT could lead to a significant reduction in the number of babies at risk for FNAIT.

In our FNAIT natural history study, we are using screening tests for maternal HPA-1 type, maternal HLA-DRB3*D1:01 status, maternal HPA-1a antibodies and fetal HPA-1 genotype.

In both the FNAIT natural history study and RLYB212 Phase 2 clinical trial, we are using screening tests for maternal HPA-1 type, maternal HLA-DRB3*01:01 status, maternal HPA-1a antibodies and fetal HPA-1 genotype.

Our solution:

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RLYB212 Clinical Development

We have completed two RLYB212 clinical trials, a Phase 1 first-in-human trial and a Phase 1b proof-of-concept trial.

The Phase 1 first-in-human clinical trial is a single-blind, placebo-controlled study that investigated the safety and PK of SC administration of RLYB212 in HPA-1a negative healthy participants.

We have completed two RLYB212 clinical trials:

a Phase 1 first-in-human clinical trial and a Phase 1b proof-of-concept clinical trial.

The Phase 1 first-in-human clinical trial was a single-blind, placebo-controlled study that investigated the safety and PK of SC administration of RLYB212 in HPA-1a negative healthy participants.

The clinical trial included a single dose cohort and a multiple dose cohort.

In the multiple dose cohort, subjects received SC RLYB212 or placebo every two weeks for 12 weeks.

An overview of the study's design is illustrated below.

Phase 1 PK and Safety Study of RLYB212 in HPA-1a Negative Healthy Participants

We reported preliminary results from the multi-dose cohort in the fourth quarter of 2023.

We reported results from the multi-dose cohort in the fourth quarter of 2023.

The data demonstrated that multiple dose PK were consistent both within and between subjects.

The data and our clinical pharmacology modeling predictions support a once monthly dosing regimen for the planned Phase 2 study.

The data and our clinical pharmacology modeling predictions support a once monthly dosing regimen for the ongoing Phase 2 trial.

RLYB212 was observed to be generally well-tolerated with no reports of injection site reactions or serious adverse events.

The Phase 1b single-blind, placebo-controlled proof-of-concept trial was designed to establish the ability of SC RLYB212 to rapidly eliminate HPA-1a positive platelets transfused to HPA-1a negative healthy subjects.

study included 11 males aged 18 to 65 years, randomized to RLYB212 0.09mg (n=4), RLYB212 0.29mg (n=5), or placebo (n=2).

An overview of the study's design is illustrated below.

Phase 1b Trial of RLYB212 in Healthy Male Participants

In June 2023, we reported the results from this clinical trial at ISTH.

The results showed that SC RLYB212 administration produced a dose-dependent, rapid and complete elimination of transfused HPA-1a positive platelets in HPA-1a negative subjects, with both doses meeting the prespecified proof-of-concept criteria of ≥90% reduction in mean platelet elimination half-life.

Mean platelet elimination half-life was 5.8 hours (0.09mg dose) and 1.5 hours (0.29mg dose) for RLYB212 compared to 71.7 hours for placebo.

Consistent with the Phase 1 first-in-human trial, RLYB212 was observed to be well-tolerated with no reports of serious or severe adverse events.

The study included 11 males aged 18 to 65 years, randomized to RLYB212 0.09 mg (n=4), RLYB212 0.29 mg (n=5), or placebo (n=2).

The study design and results are summarized below.

RLYB212 Phase 1b Trial — Design and Results

In the fourth quarter of 2024 we initiated a Phase 2 clinical trial investigating RLYB212 in pregnant women at higher risk for HPA-1a alloimmunization and FNAIT.

This is a single-arm trial that is designed to assess the PK and safety of RLYB212 in pregnant women at higher risk for HPA-1a alloimmunization and FNAIT.

Secondary objectives include assessments of pregnancy and neonatal/infant outcomes, and the occurrence of emergent HPA-1a alloimmunization.

Subcutaneous administration of RLYB212 will be initiated by Gestational Week 16 and will continue every four weeks through parturition.

The trial is designed to enroll participants in three stages:

first with a sentinel pregnant woman, an initial cohort (Cohort 1) that will include three pregnant women, and a second cohort (Cohort 2) that will include four pregnant women, for a total target enrollment of eight participants.

A data review for participants and infants is planned prior to the initiation of each cohort and continuation of the trial will be subject to evaluation of the results from each stage of the trial.

The trial will seek to enroll participants at sites across Europe.

An overview of the Phase 2 clinical trial design is illustrated below.

Phase 2 Dose Confirmation Trial of RLYB212 in Pregnant Women

Both the U.S.

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Orphan drug designations offer certain incentives including tax credits, marketing exclusivity upon any approval, fee waivers, and the ability to interact with both agencies to receive specialized regulatory advice and assistance.

We recently engaged with the EMA in such a process in advance of our planned Phase 2 clinical trial.

We received feedback from the EMA and are now moving forward with our Clinical Trial Application to support conduct of the Phase 2 study in Europe.

Based on the data generated to date and subject to completion of regulatory discussions, we plan to initiate a Phase 2 trial of RLYB212 in expectant mothers at higher FNAIT risk in the second half of 2024.

The primary objective of the Phase 2 clinical trial will be to assess the PK and safety of SC RLYB212 administered antenatally in expectant mothers.

Additional objectives will include assessing the safety of RLYB212 in the neonate and neonatal exposure of RLYB212 at time of birth, and assessing pregnancy and neonatal outcomes as well as the occurrence of emergent HPA-1a alloimmunization.

We are designing the trial as a single-arm, open-label study and plan to conduct the trial in Europe.

The intended study population is women who are at higher risk for HPA-1a alloimmunization and FNAIT (i.e., women who are identified through screening to be HPA-1a negative and HLA-DRB3*0101 positive), who are bearing an HPA-1a positive fetus and have not previously alloimmunized.

Dosing of RLYB212 will be initiated by gestational week 16 and continued at monthly intervals through pregnancy.

An overview of the study's design is illustrated below.

Phase 2 Dose Confirmation Trial of RLYB212 in Expectant Mothers

Prospective FNAIT Natural History Alloimmunization Study

We have an ongoing prospective, non-interventional, multinational natural history study.

This study is designed to screen up to 30,000 expectant mothers presenting at gestational week 10 to 14 prenatal visit

to determine the frequency of women at higher FNAIT risk among expectant mothers of different racial and ethnic characteristics, as well as the frequency of HPA-1a alloimmunization and pregnancy outcomes among these women.

As of March 1, 2024 approximately 9,400 women have been screened in the study.

This study is designed to screen expectant mothers presenting at gestational week 10 to 14 prenatal visit to determine the frequency of women at higher FNAIT risk among expectant mothers of different racial and ethnic characteristics, as well as the frequency of HPA-1a alloimmunization and pregnancy outcomes among these women.

RLYB116 for the treatment of disorders due to complement dysregulation

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RLYB116 includes an Affibody molecule, which is an antibody mimetic protein that has a much smaller molecular weight than a traditional antibody and may also be easier and less costly to produce.

In contrast to C5-targeted antibody therapeutics that are administered intravenously, RLYB116 has the potential to be administered as a small volume subcutaneous injection.

RLYB116 also includes an albumin binding domain, which may extend the half-life of the Affibody domain.

In contrast to most C5-targeted antibody therapeutics that are administered intravenously or via daily injection, RLYB116 has the potential to be administered as a small volume, once-weekly SC injection.

RLYB116 also includes an ABD, which may extend the half-life of the Affibody domain.

In addition, amino acid substitutions that are part of RLYB116 are intended to enhance its stability.

We view RLYB116 as a potential pipeline-in-a-product with disease areas under consideration including PNH, gMG and antiphospholipid syndrome.

We view RLYB116 as a potential pipeline-in-a-product with disease areas under consideration including PNH, gMG and APS.

We believe RLYB116 can address significant unmet needs for patients with these diseases by providing a potential treatment that is more accessible and patient-friendly than existing marketed products, including by reducing the frequency and improving the route of administration.

Based on our team’s experience studying and developing therapies targeting the complement system, we believe there are four important attributes that could support clinical and commercial success in the treatment of a broad range of patients suffering from complement-mediated diseases.

These include a mechanism of action targeting terminal complement, the ability to produce rapid, complete and sustained inhibition of C5, a safety profile consistent with C5 antibodies currently approved for therapeutic use, and pricing flexibility to treat a broad range of complement-mediated diseases.

We believe RLYB116 has the potential to demonstrate these attributes, and if so, could have a life-transforming impact on patients.

Given our desire to conserve capital, we may seek a partner or access to non-dilutive financing to support future clinical development.

Based on our team’s experience studying and developing therapies targeting the complement system, we believe there are five important attributes that could support clinical and commercial success in the treatment of a broad range of patients suffering from complement-mediated diseases.

These include a mechanism of action targeting terminal complement, the ability to produce rapid, complete and sustained inhibition of C5, a safety profile consistent with C5 antibodies currently approved for therapeutic use, the ability to self-administer the drug less frequently (e.g.

once per week) in an easy to use autoinjector, and pricing flexibility to treat a broad range of complement-mediated diseases.

Based on the data generated to date and the manufacturing process enhancements completed in 2024, we believe RLYB116 has the potential to demonstrate these attributes, and if so, could have a life-transforming impact on patients.

The complement system

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The binding of C5b to host cells is normally prevented by the presence of specific glycoproteins on the cell surface.

PNH disease background

PNH is a rare, potentially life-threatening hematologic disease characterized by complement-mediated destruction of red blood cells, or hemolysis.

Early signs of PNH include hemoglobinuria, or dark colored urine, resulting from excretion of hemoglobin from lysed red blood cells, which is more prominent in the morning and decreases during the day.

More serious symptoms of PNH include anemia, excessive weakness, fatigue, severe abdominal pain, severe headaches and recurrent infections.

PNH leads to over a 60-fold increase in the risk of venous thromboembolism compared to the general population and these thrombotic events lead to between 40% and 67% of deaths in PNH patients.

Approximately two thirds of patients with PNH develop chronic kidney disease ("CKD"), and kidney failure is the cause of death in 8% to 18% of patients with PNH.

In the absence of disease-modifying treatment, PNH results in the death of approximately 35% of affected individuals within five years of diagnosis.

The prevalence of PNH has been estimated to be approximately 12-13 people per million.

Current treatments for PNH and their limitations

The only curative treatment currently available for PNH is a stem cell transplant from a related donor.

However, this procedure is associated with significant risk and is typically used only in those patients with severe disease, such as life-threatening thrombosis or dangerously low blood counts.

Various supportive therapies include anticoagulants, red blood cell transfusions and supplements of iron and folate.

These therapies provide some relief from symptoms but do not address the underlying cause of the disease.

There are currently four approved disease-modifying drugs for PNH.

Although these drugs have meaningfully improved the lives of patients with PNH, they have limitations including sub-optimal delivery (three of the four

are delivered intravenously or via SC infusion) and high cost that result in limitations on access to therapy.

Despite these limitations, worldwide sales of these drugs exceeded $5 billion in 2022.

We believe that a product that works through a similar mechanism but with weekly dosing and a low-volume, convenient route of administration and improved patient access has the opportunity to further transform PNH therapy for patients.

Potential benefits of our approach

We believe PNH represents an attractive development opportunity for RLYB116 for several reasons.

First, PNH has a well-understood disease pathophysiology driven by complement, providing a sound biological rationale for a C5-targeted intervention.

Second, PNH offers the opportunity for early clinical validation using objective endpoints, including impact on lactate dehydrogenase, a component of red blood cells that is increased in circulation as a result of hemolysis.

And third – and most importantly – we believe that with a patient-friendly (small volume, once-per-week delivery using an autoinjector) and accessible therapy, RLYB116 could potentially provide transformative therapeutic impact for unserved and underserved patients with PNH globally.

gMG disease background

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During such a crisis, a decline in respiratory function can become life-threatening and require intubation and mechanical ventilation.

According to a comprehensive epidemiological study of

gMG in western Denmark from 1975-89, from the time of diagnosis, the overall survival rates at 3, 5, 10, and 20 years are estimated to be 85%, 81%, 69% and 63%, respectively.

According to a comprehensive epidemiological study of gMG in western Denmark from 1975-89, from the time of diagnosis, the overall survival rates at 3, 5, 10, and 20 years are estimated to be 85%, 81%, 69% and 63%, respectively.

Patients with gMG suffer from poor quality of life due to the impact of their disease on physical function and the burden of treatment-related adverse events.

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First, complement overactivity is known to contribute to the disease pathophysiology of gMG, providing a sound biological rationale for a C5-targeted intervention.

Second – and most importantly – our proprietary market research suggests that significant unmet need exists for more patient-friendly treatment options, which we believe could be addressed by RLYB116 as a once-weekly, small volume, self-administered subcutaneous therapeutic.

PNH disease background

PNH is a rare, potentially life-threatening hematologic disease characterized by complement-mediated destruction of red blood cells, or hemolysis.

More serious symptoms of PNH include anemia, excessive weakness, fatigue, severe abdominal pain, severe headaches and recurrent infections.

PNH leads to over a 60-fold increase in the risk of venous thromboembolism compared to the general population and these thrombotic events lead to between 40% and 67% of deaths in PNH patients.

Approximately two thirds of patients with PNH develop chronic kidney disease ("CKD"), and kidney failure is the cause of death in 8% to 18% of patients with PNH.

In the absence of disease-modifying treatment, PNH results in the death of approximately 35% of affected individuals within five years of diagnosis.

The prevalence of PNH has been estimated to be approximately 12-13 people per million.

Current treatments for PNH and their limitations

The only curative treatment currently available for PNH is a stem cell transplant from a related donor.

However, this procedure is associated with significant risk and is typically used only in those patients with severe disease, such as life-threatening thrombosis or dangerously low blood counts.

Various supportive therapies include anticoagulants, red blood cell transfusions and supplements of iron and folate.

These therapies provide some relief from symptoms but do not address the underlying cause of the disease.

There are currently four approved disease-modifying drugs for PNH.

Although these drugs have meaningfully improved the lives of patients with PNH, they have limitations including sub-optimal delivery (three of the four are delivered intravenously or via subcutaneous infusion) and high cost that result in limitations on access to therapy.

Despite these limitations, worldwide sales of these drugs exceeded $5 billion in 2022.

APS disease background

APS is a potentially life-threatening, rare autoimmune disorder in which an individual's immune system mistakenly creates antiphospholipid antibodies that can lead to the formation of blood clots.

Blood clots can occur in the legs, lungs, brain, and other organs, such as the kidneys and spleen.

The clots can lead to a heart attack or a stroke.

During pregnancy, women with APS are also at increased risk of miscarriage.

APS can occur on its own but can also occur secondary to other autoimmune diseases such as systemic lupus erythematosus.

APS affects three to five times as many women as men and is most often diagnosed in people between the ages of 30 and 50.

It is estimated that there are >130,000 people in the US and >120,000 in Europe who suffer from APS.

Current treatments for APS and their limitations

Currently, there is no cure for APS.

However, medicines including blood thinners such as warfarin or heparin can help prevent health problems caused by the disease.

The goals of treatment are to prevent blood clots from forming and to keep existing clots from increasing in size.

However, direct oral anticoagulants are generally less effective in preventing recurrent thromboembolic events, most notably strokes.

Potential benefits of our approach

We believe PNH represents an attractive development opportunity for RLYB116 for several reasons.

First, PNH has a well-understood disease pathophysiology driven by complement, providing a sound biological

rationale for a C5-targeted intervention.

And third – and most importantly – we believe that with a patient-friendly and accessible therapy, RLYB116 could potentially provide transformative therapeutic impact for unserved and underserved patients with PNH globally.

We are pursuing APS as part of our initial development strategy for two reasons.

First, there is significant unmet need in patients with primary and secondary APS who continue to suffer from thrombotic events despite standard anticoagulation therapy.

Second, we believe that RLYB116 has the potential to be an effective treatment for this patient population.

Complement overactivity likely contributes to the disease pathophysiology, providing a sound biological rationale for a C5-targeted intervention, and case reports evaluating the use of C5 inhibitors in patients experiencing recurrent thrombotic events despite standard anticoagulation therapy have demonstrated clinical benefit.

RLYB116 as a once-weekly, small volume, self-administered subcutaneous therapeutics could represent a safe, effective, and patient-friendly option for APS patients with an inadequate response to standard of care.

Our solution:

RLYB116 is an engineered protein that includes an Affibody molecule and an albumin binding domain.

RLYB116 is an engineered protein that includes an Affibody molecule and an ABD.

We acquired rights to RLYB116 from Swedish Orphan Biovitrum AB (Publ) ("Sobi").

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The low molecular weight allows for a higher concentration of active molecules than antibodies in an equivalent volume.

This increases the probability of being able to deliver RLYB116 in a volume suitable for subcutaneous administration.

This increases the probability of being able to deliver RLYB116 in a volume suitable for SC administration in a patient friendly format such as an autoinjector.

• Efficiency of manufacturing.

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• Less frequent dosing .

Linkage of the Affibody domain to an albumin binding domain may lengthen the dosing interval of RLYB116 by extending the biological half-life.

Linkage of the Affibody domain to an ABD may lengthen the dosing interval of RLYB116 by extending the biological half-life and offer potential dosing benefits to patients.

• Potentially lower risk of treatment conversion .

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The SAD design was a single-blind, placebo-controlled, dose escalation trial investigating the safety, PK and PD of single dose RLYB116 in healthy participants.

The SAD portion of the Phase 1 trial included five sequential ascending dose cohorts with doses ranging from 2mg up to 300mg, each enrolling 8 subjects (6 treated with RLYB116 and 2 with placebo) with a 10 week post-treatment / safety follow-up period.

The SAD portion of the Phase 1 trial included five sequential ascending dose cohorts with doses ranging from 2mg up to 300mg, each enrolling eight subjects (six treated with RLYB116 and two with placebo) with a 10 week post-treatment / safety follow-up period.

An overview of the clinical trial’s design is illustrated below.

Design of the Phase 1 Clinical Trial of RLYB116 in Healthy Participants (Single Ascending Dose)

Completed Phase 1 Clinical Trial of RLYB116 in Healthy Participants (Single Ascending Dose)

Data from the SAD portion of the trial showed consistent increases in exposure with increasing dose levels, low inter-subject variability, and a mean elimination half-life greater than 300 hours after a single SC, low volume injection.

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The MAD portion of the trial included four cohorts:

Design of the Phase 1 Clinical Trial of RLYB116 in Healthy Participants (Multiple Ascending Dose)

Cohort 1 (weekly dosing of 100 mg), Cohort 2 (three doses of 100 mg the first week followed by weekly dosing), Cohort 3 (150 mg weekly dosing reduced to 125 mg weekly dosing) and Cohort 4 (75 mg twice the first week followed by 100 mg twice per week) with post-treatment / study follow-up for 10 weeks.

Completed Phase 1 Clinical Trial of RLYB116 in Healthy Participants (Multiple Ascending Dose)

In December 2023, we reported data from the MAD portion of the Phase 1 trial that demonstrated a 100 mg low volume (1 mL) once-weekly dose of subcutaneously administered RLYB116 achieved sustained mean reductions in free C5 of greater than 93%, including at day 29 with measurement prior to the last dose.

The reduction in free C5 at 24 hours after the first dose of 100 mg was greater than 99%.

In the MAD portion of the Phase 1 trial, RLYB116 also demonstrated low inter-subject variability and consistent increases in exposure

relative to dose with a mean estimated elimination half-life for RLYB116 of >300 hours.

In the MAD portion of the Phase 1 trial, RLYB116 also demonstrated low inter-subject variability and consistent increases in exposure relative to dose with a mean estimated elimination half-life for RLYB116 of >300 hours.

RLYB116 administered as a 100 mg once-weekly dose was also observed to be generally well tolerated.

Across the MAD portion of the trial, injection site reaction (ISR) was the most common adverse event (all mild in severity) and gastrointestinal adverse events increased with increasing dose.

Across the MAD portion of the trial, injection site reaction (ISR) was the most common adverse event (all mild in severity) and gastrointestinal

adverse events increased with increasing dose.

There was one case of severe liver function test ("LFT") elevation in Cohort 3 in a participant with a history of hepatitis that resulted in discontinuation of treatment.

Finally, the measurement of anti-drug antibody ("ADA") formation in the study did not demonstrate an effect on PK or PD parameters and did not appear to be associated with an effect on the severity or incidence of adverse events.

In December 2023, we announced that we would not immediately initiate a Phase 2 clinical trial of RLYB116 for the treatment of gMG, and would prioritize near-term program investments in the RLYB116 manufacturing process.

We expect that the additional manufacturing work will improve tolerability at higher doses with a low injection volume and infrequent SC administration, which will enable higher exposure to RLYB116 and potentially increase C5 reduction.

If successful, we believe the anticipated manufacturing enhancements will expand the opportunity to treat a broader range of complement-mediated diseases, including PNH and antiphospholipid syndrome.

Based on the results of the RLYB116 Phase 1 trial, we conducted a series of biomarker characterization analyses.

We now believe that RLYB116 has the potential to be an effective treatment for patients with a variety of complement-mediated diseases, including PNH, gMG and APS.

We also completed manufacturing process enhancements with a goal of further improving the tolerability of RLYB116.

Based on the results of enhanced analytical techniques, including mass spectrometry, these process enhancements have successfully further purified the RLYB116 drug substance.

As a result, we believe that RLYB116 will have a favorable tolerability profile at doses at and above those evaluated in the Phase 1 MAD trial.

We plan to initiate a RLYB116 confirmatory clinical PK/PD trial in the second quarter of 2025 to demonstrate improved tolerability as well as complete and sustained complement inhibition.

This single-blind MAD trial will evaluate a 4-week treatment duration that will include two cohorts of eight participants each.

Our current plan is that Cohort 1 will evaluate weekly dosing of 150 mg and Cohort 2 will evaluate weekly dosing of 225 mg with 10 weeks of follow-up after the conclusion of treatment.

The planned confirmatory trial is summarized below:

Planned Confirmatory Multiple Ascending Dose Phase 1 Clinical Trial of RLYB116 in Healthy Participants

Based on market research conducted to date, we believe that an effective, once-weekly, well-tolerated therapy that can be rapidly self-administered with an autoinjector would be an attractive alternative for patients suffering from gMG and other complement mediated diseases.

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Reasons for this limited efficacy are unknown but could include the disease stage, level of intervention in the complement pathway, drug delivery mechanism and the ability of the therapeutic to cross Bruch’s membrane and the retinal pigment epithelium.

Our solution:

In February 2023, we entered into a collaboration with EyePoint.

We are evaluating RLYB114 with EyePoint’s proprietary technology for sustained intraocular drug delivery, with the initial focus on geographic atrophy, an advanced form of age-related macular degeneration that leads to irreversible vision loss.

We and EyePoint expect to provide an update on this collaboration in the first half of 2024.

Our research collaboration with EyePoint Pharmaceuticals to evaluate delivery of RLYB114 using EyePoint’s technology for sustained intraocular drug delivery ended in January 2025.

RLYB332 for the treatment of severe anemia with ineffective erythropoiesis and iron overload

In May 2022, we obtained worldwide exclusive rights to RLYB331, a preclinical antibody.

We believe RLYB331 has the potential to address a significant unmet need for patients with severe anemias with ineffective erythropoiesis and iron overload, including beta thalassemia and a subset of lower risk myelodysplastic syndromes.

Currently these patients are underserved by the existing standard of care.

RLYB331 is a monoclonal antibody that is designed to inhibit MTP-2.

In May 2022, we obtained worldwide exclusive rights to RLYB331, a preclinical antibody designed to inhibit MTP-2.

The inhibition of MTP-2 significantly increases levels of hepcidin, decreases iron load and treats ineffective erythropoiesis.

We are continuing with preclinical activities to support the transition of this asset into clinical development and expect to report additional animal data from this program in the first half of 2024.

AI drug discovery collaboration with Exscientia

We established a partnership with Exscientia, an AI and machine learning drug discovery company.

We believe this molecule has the potential to address a significant unmet need for

patients with severe anemias with ineffective erythropoiesis and iron overload, including beta thalassemia and a subset of lower risk MDS.

Currently these patients are underserved by the existing standard of care.

In 2024, we completed non-clinical studies that demonstrated favorable tolerability, dose-dependent PK, and sustained PD effects with RLYB332, a long-acting version of RLYB331.

These findings, which were presented in a poster at the 66th annual meeting of ASH, support the continued development of RLYB332 as a potentially best-in-class therapeutic for treating diseases of iron overload.

Given the potential value of this program, we are currently assessing the most effective way to move this program through preclinical development towards a potential investigational new drug ("IND") application filing.

AI drug discovery collaboration with Recursion

We established a partnership with Exscientia (acquired by Recursion), an AI and machine learning drug discovery company.

Our partnership currently consists of a joint venture that is focused on the discovery and development of small molecules for the treatment of patients with rare metabolic diseases.

We are initially targeting ENPP1, an

enzyme involved in regulating extracellular levels of pyrophosphate, a natural inhibitor of calcium mineralization in bone formation, for the treatment of patients with HPP.

We are targeting ENPP1, an enzyme involved in regulating extracellular levels of pyrophosphate, a natural inhibitor of calcium mineralization in bone formation, for the treatment of patients with HPP.

RE Ventures I, LLC :

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We believe that controlling inhibition of ENPP1 may reduce PPi levels and restore balance within the bone mineralization process.

In 2024, we identified and advanced REV102, an ENPP1 inhibitor for the treatment of patients with HPP.

We also presented data at the ASBMR from an early lead ENPP1 inhibitor, REV101, in a mouse model of later-onset HPP demonstrating a 30% reduction in inorganic PPi, a key biomarker that is elevated in HPP and contributes to poor bone mineralization.

HPP disease overview

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However, Strensiq has limitations, including its dosing regimen and patient access.

Strensiq is administered by subcutaneous injection either three or six times per week using a weight-based dosing scale, which can be both onerous and painful for patients.

Strensiq is administered by SC injection either three or six times per week using a weight-based dosing scale, which can be both onerous and painful for patients.

Our solution:

an ENPP1 small molecule inhibitor

We are developing an orally available, small molecule ENPP1 inhibitor designed to reduce PPi levels through the controlled inhibition of ENPP1, which we hypothesize may restore the balance of PPi and phosphate needed to promote bone mineralization.

We and Exscientia expect to select a small molecule development candidate to advance into clinical development.

Proof of mechanism studies are in progress with a leading global HPP expert.

We plan to provide an update on the progress of the program in the second half of 2024.

REV102, an ENPP1 small molecule inhibitor

REV102 is an orally available small molecule inhibitor of ENPP1 for the treatment of patients with HPP.

We are developing REV102 to be a safe, tolerable, and accessible option for juvenile- and adult-onset HPP patients as either monotherapy or add-on therapy to ERT.

We believe that REV102 has the potential to address a

significant unmet need for patients and plan to conduct IND-enabling studies in 2025 to support the initiation of a Phase 1 trial in 2026.

Scientific Rational:

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AbCellera and Rallybio intend to co-develop up to five rare disease therapeutic targets, which will be chosen together by both companies.

The partnership’s first program is focused on addressing the significant unmet therapeutic needs of patients with rare metabolic diseases.

The biotechnology and pharmaceutical industries are highly competitive and subject to significant and rapid technological change.

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Companies that currently market IVIG include ADMA Biologics, Bio Products Laboratory, CSL Behring, Grifols, Kedrion Biopharma, Leadiant Biosciences, Octapharma and Takeda Pharmaceutical Company Limited.

Very early-stage gMG is symptomatically treated by the use of acetylcholinesterase inhibitors such as pyridostigmine bromide, marketed as Mestinon by Bausch Health.

Eculizumab and ravulizumab are also approved for the treatment of gMG in patients who are positive for anti-AChR antibodies.

Efgartigimod, marketed as Vyvgart by Argenx SE, is a neonatal Fc receptor blocker also approved for the treatment of patients with generalized MG who are positive for anti-AChR antibodies and Zilbrysq, a macrocyclic peptide marketed by UCB Pharma was approved for the treatment of AChR+ adult patients with gMG.

Rozanolixizumab, marketed as Rystiggo by UCB, is a neonatal Fc receptor blocker approved for the treatment of gMG in adult patients who are AChR+ or anti-MuSK antibody positive.

There are several other companies developing assets in mid- to late-stage clinical development for the treatment of gMG using a variety of approaches and modalities.

These companies include AstraZeneca, Horizon Therapeutics (acquired by Amgen Inc.) and Immunovant, Inc.

In another approach, to treat FNAIT (which is different than Rallybio's approach to prevent FNAIT), Johnson & Johnson is currently evaluating the effectiveness of nipocalimab (compared with placebo) to reduce the risk of FNAIT in women that have a history of at least one prior FNAIT-affected pregnancy.

The only curative treatment currently available for PNH is a stem cell transplant from a related donor.

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These therapies provide some relief from symptoms but do not address the underlying cause of the disease.

There are four approved

drugs for PNH:

There are four approved drugs for PNH:

eculizumab, marketed by AstraZeneca as Soliris;

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among others.

Very early-stage gMG is symptomatically treated by the use of acetylcholinesterase inhibitors such as pyridostigmine bromide, marketed as Mestinon by Bausch Health.

Eculizumab and ravulizumab are also approved for the treatment of gMG in patients who are positive for anti-AChR antibodies.

Rozanolixizumab, marketed as Rystiggo by UCB, is a neonatal Fc receptor blocker approved for the treatment of gMG in adult patients who are AChR+ or anti-MuSK antibody positive.

There are several other companies developing assets in mid- to late-stage clinical development for the treatment of gMG using a variety of approaches and modalities.

These companies include AstraZeneca, Horizon Therapeutics (acquired by Amgen Inc.) and Immunovant, Inc.

There is one approved treatment for HPP, asfotase alfa, marketed by AstraZeneca as Strensiq, which is an alkaline phosphotase enzyme replacement therapy, and the only approved therapy for the treatment of perinatal-, infantile- and juvenile-onset HPP.

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with all these companies in discovery or preclinical development.

We are not aware of other small molecule inhibitors in development for the treatment of patients with HPP.

Alesta Therapeutics B.V.

recently announced work on an ENPP1 small molecule inhibitor for the treatment of patients with HPP.

Many of our competitors may have significantly greater name recognition and financial, manufacturing, marketing, product development, technical, commercial infrastructure, and human resources than we do.

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In addition, because of the significant amount of time required for clinical development and regulatory review of product candidates, we cannot be certain that any of our product candidates will be commercialized while there is significant patent term remaining on patents relating to those products.

The term of a patent depends upon the legal requirements for determination of patent term in the

country in which that patent is granted.

The term of a patent depends upon the legal requirements for determination of patent term in the country in which that patent is granted.

In most countries, including the United States, the patent term is 20 years from the earliest claimed filing date of a non-provisional patent application.

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We also cannot be certain that any of our activities will not be subject to the intellectual property rights of others.

As of March 1, 2024, we owned two patent families that were acquired from Prophylix AS ("Prophylix") and relate to the current product candidates in our FNAIT prevention program, RLYB211 and RLYB212.

As of March 1, 2025, we owned two patent families that were acquired from Prophylix AS ("Prophylix") and relate to product candidates in our FNAIT prevention program, RLYB211 and RLYB212.

The acquired patent family covering RLYB212 and its use in treating and preventing FNAIT includes patents issued or accepted in Australia, Canada, Europe, Israel, Mexico, New Zealand, Russia, and the United States.

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Patents issuing in these two families will have an expiration date of June 2042, excluding any PTA or PTE that may be awarded.

The third family is a pending United States provisional patent application.

In addition, we filed and own two pending International (PCT) patent applications, one directed to assays for quantifying anti-HPA1a antibodies and the other directed to the formulation of RLYB212.

We also exclusively in-license certain rights to technology from Versiti Blood Research Institute Foundation, Inc.

The third family is a pending International (PCT) patent application.

In addition, we filed and own a patent family directed to assays for quantifying anti-HPA1a

antibodies, with patent applications pending in Australia, Brazil, Canada, Europe, Israel, Mexico, New Zealand, South Africa and the United States.

We also filed and own a pending International (PCT) application directed to the formulation of RLYB212.

In addition, we exclusively in-license certain rights to technology from Versiti Blood Research Institute Foundation, Inc.

pertaining to a mouse model of FNAIT.

As of March 1, 2025, we owned two patent families relating to the current product candidates in our complement program, RLYB114 and RLYB116, and certain aspects of their use that were acquired from Sobi.

These two patent families currently include four granted U.S.

These two patent families currently include five granted U.S.

patents and one pending U.S.

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In the United States, Australia, Canada the European Patent Convention contracting states, and Japan, applications in both patent families have been granted and are scheduled to expire between 2033 and 2034, excluding any PTA or PTE.

In addition, we filed and own a pending International (PCT) patent application directed to dosing and administration of RLYB116, and six pending provisional patent applications directed to methods of treatment of various C5-related conditions by administration of RLYB116.

We have also non-exclusively in-licensed certain

patent rights relating to our current product candidates from Affibody, including patent rights relating to the Affibody molecule technology and Albumod albumin binding molecule technology.

In addition, we filed and own a family of patent applications directed to dosing and administration of RLYB116 that consists of pending patent applications in Australia, Canada, Europe, Japan, the United States and 22 additional countries.

Patents issuing in this patent family will have an expiration date in November 2042, excluding any PTA or PTE that may be awarded.

We also filed and own eight pending provisional patent applications directed to methods of treatment of various C5-related conditions by administration of RLYB116.

We have also non-exclusively in-licensed certain patent rights relating to our current product candidates from Affibody, including patent rights relating to the Affibody molecule technology and Albumod albumin binding molecule technology.

As of March 1, 2025, we exclusively in-licensed from Kymab Limited certain patent rights to the current product candidate in our iron overload program, RLYB332, as well as back-up compounds.

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The patent family currently includes pending patent applications in the United States and in more than 20 other countries/regions, including Australia, Brazil, Canada, China, Eurasia, Europe, India, Japan, Mexico, and Saudi Arabia.

In addition, we have non-exclusively in-licensed from Kymab Limited certain patent rights relating to the development, manufacture, and use of RLYB331 and the back-up compounds.

In addition, we filed and own a pending International (PCT) patent application family directed to use of RLYB332 for treating pathologies of beta-thalassemia.

Further, we have non-exclusively in-licensed from Kymab Limited certain patent rights relating to the development, manufacture, and use of RLYB332 and the back-up compounds.

License Agreements

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In March 2019, our subsidiary IPC Research, LLC ("IPC Research") and Sobi entered into a Contract Assignment Agreement pursuant to which Sobi assigned to, and IPC Research assumed, all obligations in a certain Product License Agreement ("PLA") as amended, between Sobi and Affibody AB ("Affibody"), dated March 9, 2012, as amended on January 1, 2018 and December 22, 2020.

Pursuant to the PLA, we obtained a license to the Affibody platform technology and a particular albumin binding domain ("ABD"), in order to further develop and commercialize certain Affibody ligands, which we are now developing as RLYB116 and RLYB114.

Pursuant to the PLA, we obtained a license to the Affibody platform technology and a particular ABD, in order to further develop and commercialize certain Affibody ligands, which we are now developing as RLYB116 and RLYB114.

Under the PLA, Affibody grants us (1) a non-exclusive right under certain patents to use the Affibody ligands alone or as a fusion protein and (2) an exclusive right to use the Affibody ligands alone or as a fusion protein, in each case, for human therapeutic use.

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Our obligation to pay royalties expires, on a country-by-country and product-by-product basis, on the later of (a) the 10th anniversary following first commercial sale of such product in such country and (b) the expiration date in such country of the last to expire of any issued patent included in the patent rights acquired from Sobi that includes at least one valid claim covering the sale of such product in such country.

We are obligated to use commercially reasonable efforts to research, develop and exploit at least one product that contains a compound transferred under the agreement as an active ingredient in each of the United States, EU and Japan.

If, prior to the commercial launch in the United States of the first product containing the compounds, we decide to divest our rights in the assets acquired from Sobi or to terminate all research, development and commercialization activities in respect of the acquired compounds, we must notify Sobi and negotiate in good faith with Sobi a possible business transaction relating to the assets.

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If, after using commercially reasonable efforts to develop and commercialize products containing plasma-derived anti-HPA-1a immunoglobulin and the monoclonal antibody in the United States and in at least one major European market, we decide not to pursue any further development or commercialization activities for such products, then Prophylix will have the right to repurchase the remaining assets acquired under the agreement for approximately $1.2 million.

Prophylix also will have the right to repurchase the remaining assets acquired under the agreement for approximately $1.2 million if we elect to transfer all or substantially all of the

assets acquired under the agreement to a third-party who does not agree to assume our obligations to develop and commercialize the products.

Prophylix also will have the right to repurchase the remaining assets acquired under the agreement for approximately $1.2 million if we elect to transfer all or substantially all of the assets acquired under the agreement to a third-party who does not agree to assume our obligations to develop and commercialize the products.

Joint Venture Agreement

In July 2019, we entered into a partnership with Exscientia and created RE Ventures I, LLC ("RE Ventures"), which is jointly owned by Exscientia and one of our wholly-owned subsidiaries, each a Member and collectively the Members.

In July 2019, we entered into a partnership with Recursion (as successor in interest to Exscientia) and created RE Ventures I, LLC ("REV-I"), which is jointly owned by Recursion and one of our wholly-owned subsidiaries, each a Member and collectively the Members.

The joint venture was formed to initiate early-stage drug discovery of orally available small molecules targeting ENPP1 for the treatment of HPP, and thereafter for the future research, development, manufacture, sale and exploitation of any company-owned technology and compounds, including any resulting compound identified by the steering committee of the joint venture.

Under the RE Ventures operating agreement, we received a 50% interest in the joint venture in exchange for an initial contribution of £0.5 million ($0.6 million, based on the exchange rate at the time).

RE Ventures used this initial capital to fund stage 1 of the ENPP1 program, and we committed to fund additional amounts if costs of stage 1 exceeded the initial funding.

In June 2020, RE Ventures determined that the stage 1 objective of discovering compounds for ENPP1 with a certain potency had been achieved.

In 2020, we contributed £ 1.1 million ($1.3 million, based on the exchange rate at the time) and in 2021, we contributed approximately £1.4 million ($2.0 million, based on the exchange rate at the time) to RE Ventures in support of ongoing Stage 2 development of the ENPP1 program.

In 2022, we contributed £0.2 million ($0.3 million, based on the exchange rate at the time) and in 2023, we contributed £1.8 million ($2.3 million, based on the exchange rate at the time) to RE Ventures in support of ongoing development of the ENPP1 program.

The board of managers of RE Ventures may determine from time to time that additional capital is necessary or appropriate to enable RE Ventures to conduct its activities, and may seek (but not require) additional capital contributions from the Members.

In the event that either Member does not fund a portion of committed additional amounts, the other Member may contribute the unfunded amount and the respective membership interests in RE Ventures will be adjusted accordingly.

A steering committee is responsible for oversight of RE Ventures’ research and deployment plans as well as intellectual property and regulatory matters.

A two-person board of managers manages the business and affairs of RE Ventures and is responsible for all management and other responsibilities not specifically reserved to the steering committee or to the Members.

Under the REV-I operating agreement, we received a 50% interest in the joint venture in exchange for an initial contribution of £0.5 million ($0.6 million, based on the exchange rate at the time).

REV-I used this initial capital to fund stage 1 of the ENPP1 program, and we committed to fund additional amounts if costs of stage 1 exceeded the initial funding.

In June 2020, REV-I determined that the stage 1 objective of discovering compounds for ENPP1 with a certain potency had been achieved.

In 2020, we contributed £ 1.1 million ($1.3 million, based on the exchange rate at the time) and in 2021, we contributed approximately £1.4 million ($2.0 million, based on the exchange rate at the time) to REV-I in support of ongoing Stage 2 development of the ENPP1 program.

In 2022, we contributed £0.2 million ($0.3 million, based on the exchange rate at the time), in 2023, we contributed £1.8 million ($2.3 million, based on the exchange rate at the time) and in 2024 we contributed £1.6 million ($2.0 million, based on the exchange rate at the time) to REV-I in support of ongoing development of the ENPP1 program.

The board of managers of REV-I may determine from time to time that additional capital is necessary or appropriate to enable REV-I to conduct its activities, and may seek (but not require) additional capital contributions from the Members.

A steering committee is responsible for oversight of REV-I’s research and deployment plans as well as intellectual property and regulatory matters.

A two-person board of managers manages the business and affairs of REV-I and is responsible for all management and other responsibilities not specifically reserved to the steering committee or to the Members.

Each Member designates one member to the board.

Each Member is subject to customary restrictions on its transfer of interests in RE Ventures, including a right of first refusal, co-sale right and drag-along provision.

Each Member is subject to customary restrictions on its transfer of interests in REV-I, including a right of first refusal, co-sale right and drag-along provision.

AbCellera Collaboration Agreement

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The collaboration will allow Rallybio to add product candidates to its existing pipeline and also provides the option for AbCellera to conduct process development and clinical manufacturing activities.

The partnership’s first program will focus on addressing the significant unmet therapeutic needs of patients with rare metabolic diseases.

Collaboration Agreement with Johnson & Johnson

In April 2024, through Rallybio IPA, we entered into a collaboration agreement (the “J&J Collaboration Agreement”) with Johnson & Johnson, through its wholly-owned subsidiary, Momenta Pharmaceuticals, Inc.

Under the J&J Collaboration Agreement, the Company and J&J will advance therapeutic solutions for pregnant individuals at risk of FNAIT.

The Company will share certain aggregated, anonymized data with J&J, collected from the Company’s FNAIT natural history study and the Company’s Phase 2 FNAIT clinical trial, where the Phase 2 data will be restricted to certain natural history data in support of the FNAIT natural history study.

The Company also agreed to disseminate information to its FNAIT study sites related to J&J’s and its affiliates’ research and development of complementary therapeutic approaches aimed at reducing the risk of FNAIT.

Under the terms of the J&J Collaboration Agreement, J&J made an upfront payment of $0.5 million.

The Company is also eligible to receive additional payments of up to an aggregate of $3.7 million, based upon certain triggers relating to the FNAIT studies and the Company’s activities under the agreement.

The J&J Collaboration Agreement expires in April 2026.

The Company may terminate the agreement upon J&J’s material breach, the Company’s decision to discontinue an FNAIT study, or during a certain part of the term if the Company determines for any reason that termination of the agreement is in the best interests of the Company.

J&J may terminate the agreement upon the Company’s material, uncured breach, upon the Company’s decision to discontinue an FNAIT study, documented failure of the Company to conduct its FNAIT studies in accordance with applicable law and J&J’s decision to discontinue its FNAIT studies.

Manufacturing and Supply

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We currently rely on multiple CMOs for all of our preclinical and clinical supply requirements, including drug substances and drug products, and label and packaging for our preclinical research and clinical trials.

We believe that we will be able to contract with other CMOs to manufacture drug substances if our existing sources

of drug substances were no longer available to us or with sufficient capacity, but there is no assurance that the drug substance capacity would be available from other CMOs on acceptable terms, on the timeframe that our business would require, or at all.

We believe that we will be able to contract with other CMOs to manufacture drug substances if our existing sources of drug substances were no longer available to us or with sufficient capacity, but there is no assurance that the drug substance capacity would be available from other CMOs on acceptable terms, on the timeframe that our business would require, or at all.

We do not currently have supply commitments or other arrangements in place with our existing CMOs.

We do not have any current contractual relationships for the manufacture of commercial supplies of any of our product candidates if they are approved by the regulatory authorities, and we intend to enter into agreements with a CMO and one or more back-up manufacturers for the commercial production of our product candidates as they near phase 3 clinical trials.

We do not have any current contractual relationships for the manufacture of commercial supplies of any of our product candidates if they are approved by the regulatory authorities, and we intend to enter into agreements with a CMO and plans for one or more back-up manufacturers for the commercial production of our product candidates as they near phase 3 clinical trials.

Any products to be used in clinical trials and any approved product that we may commercialize will need to be manufactured in facilities, and by processes, that comply with the FDA’s current Good Manufacturing Practice ("cGMP") requirements and comparable requirements of the regulatory agencies of other jurisdictions in which we are seeking approval.

We currently employ internal resources to manage our CMOs.

We believe that RLYB212, RLYB116, RLYB114, and RLYB331 can be manufactured through reliable and reproducible biologic and chemical processes from readily available starting materials.

We believe that RLYB212, RLYB116, REV102 and RLYB332 can be manufactured through reliable and reproducible biologic and chemical processes from readily available starting materials.

We believe that our manufacturing processes are amenable to scale-up and will not require unusual or expensive equipment.

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• manufacture and testing of the therapeutic or biologic moiety and its respective product formulation according to cGMP regulations or other applicable regulations;

• submission to the FDA of an investigational new drug application ("IND"), which must become effective before human clinical trials may begin and must be updated annually and amended when certain changes are made;

• submission to the FDA of an IND application, which must become effective before human clinical trials may begin ;

• approval by an independent institutional review board ("IRB") or ethics committee representing each clinical trial site before each clinical trial may be initiated;

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• review of the NDA or BLA by an FDA advisory committee, where applicable;

• satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the drug or biologic and its respective finished product is produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

• satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the drug or biologic and its respective finished product is produced ;

• satisfactory completion of any FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data submitted in support of the NDA or BLA;

• FDA review and approval of the NDA or BLA, which may be subject to additional post- approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy ("REMS") and any other potential post- approval studies required by the FDA.

• FDA review and approval of the NDA or BLA.

Preclinical Studies and IND

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An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time, the FDA raises concerns or questions related to one or more proposed clinical trials and places the clinical trial on a clinical hold.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

Imposition of a clinical hold could cause significant delays or difficulties in initiating and/or completing planned clinical trials in a timely manner.

In such a case, the IND sponsor and the

FDA must resolve any outstanding concerns before the clinical trial can begin.

Certain long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may initiate or continue after an IND for an investigational product candidate is submitted to the FDA and human clinical trials have been initiated.

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Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee.

This group may recommend continuation of the trial as planned, changes in trial conduct or cessation of the trial at designated checkpoints

based on access to certain data from the study.

This group may recommend continuation of the trial as planned, changes in trial conduct or cessation of the trial at designated checkpoints based on access to certain data from the study.

The FDA may at any time while clinical trials are ongoing impose a partial or complete clinical hold based on concerns for patient safety and/or noncompliance with regulatory requirements.

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Human clinical trials to evaluate therapeutic indications to support NDAs and BLAs for marketing approval are typically conducted in three sequential phases that may overlap or be combined:

The product candidate is initially introduced into human subjects and tested for safety, dosage tolerance, absorption, metabolism, distribution, and excretion, and if possible, to gain early evidence for effectiveness.

Phase 1 trials may be conducted in healthy volunteers or, in the case of some products for severe or life-threatening diseases, including many rare diseases, the initial human testing is often conducted in patients with the target disease or condition.

The product candidate is initially introduced into human subjects, who are commonly healthy volunteers, and tested for safety, dosage tolerance, absorption, metabolism, distribution, and excretion, and if possible, to gain early evidence for effectiveness.

Clinical trials are conducted in a limited patient population with a specified disease or condition to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.

Clinical trials are undertaken with an expanded patient population to further evaluate dosage, and to provide substantial evidence of clinical efficacy and safety in an expanded patient population, often at geographically dispersed clinical study sites.

These studies are intended to establish the overall risk-benefit ratio of the product candidate and provide, if appropriate, an adequate basis for product labeling.

These trials may include comparisons with placebo and/or other comparator treatments.

The duration of treatment is often extended to mimic the actual use of a product during marketing.

Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval.

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Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the clinical protocol, GCP or other IRB requirements or if the drug has been associated with unexpected serious harm to patients.

Information about certain clinical trials, including details of the protocol and eventually study results, also must be submitted within specific time frames to the National Institutes of Health for public dissemination on the ClinicalTrials.gov data registry.

Similar requirements for posting clinical trial information in clinical trial registries exist in the EU and in other countries outside the United States.

During the development of a new drug or biological product, sponsors have the opportunity to meet with the FDA at certain points, including prior to submission of an IND, at the end of phase 2 and before submission of an NDA or BLA.

These meetings can provide an opportunity for the sponsor to share information about the data gathered to date and for the FDA to provide advice on the next phase of development.

Concurrent with clinical trials, companies usually complete additional nonclinical studies and must also develop additional information about the physical characteristics of the drug or biological product and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

Concurrent with clinical trials, companies usually complete additional non-clinical studies and must also develop additional information about the physical characteristics of the drug or biological product and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality, potency and purity of the final drug or biological product.

For biological products in particular, the PHSA

emphasizes the importance of manufacturing controls for products whose attributes cannot be precisely defined in order to help ensure safety, purity and potency.

Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

For biological products in particular, the PHSA emphasizes the importance of manufacturing controls for products whose attributes cannot be precisely defined in order to help ensure safety, purity and potency.

Marketing Application Submission and FDA Review

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In this event, the application must be resubmitted with the additional information.

The resubmitted application is also subject to review before the FDA accepts it for filing.

After the submission is accepted for filing, the FDA begins an in-depth substantive review of the application.

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The FDA is not bound by the recommendation of an advisory committee, but it considers such recommendations when making final decisions on approval.

The FDA also may require submission of a REMS, if it determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks and to assure the safe use of the drug or biological product.

The FDA also may require submission of a Risk Evaluation and Mitigation Strategy ("REMS"), if it determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks and to assure the safe use of the drug or biological product.

If the FDA concludes a REMS is needed, the sponsor of the NDA or BLA must submit a proposed REMS and the FDA will not approve the NDA or BLA without a REMS.

Under the Pediatric Research Equity Act of 2003 ("PREA"), an NDA or BLA or certain supplements thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective, unless this requirement is waived, deferred or inapplicable.

Sponsors must submit a pediatric study plan to FDA outlining the proposed pediatric study or

studies they plan to conduct, including study objectives and design, any deferral or waiver requests and other information required by regulation.

Sponsors must submit a pediatric study plan to FDA outlining the proposed pediatric study or studies they plan to conduct, including study objectives and design, any deferral or waiver requests and other information required by regulation.

The FDA must then review the information submitted, consult with the sponsor and agree upon a final plan.

The FDA or the applicant may request an amendment to the plan at any time.

In general, PREA requirements do not apply to drugs or biologics for indications granted orphan drug designation by the FDA.

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The approval process is lengthy and often difficult, and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteria are not satisfied or may require additional clinical or other data and information.

After evaluating the application and all related information, including the advisory committee recommendations, if any, and inspection reports of manufacturing facilities and clinical trial sites, the FDA may issue either an approval letter or a Complete Response Letter ("CRL").

After evaluating the application and all related information, the FDA may issue either an approval letter or a Complete Response Letter ("CRL").

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

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A CRL generally outlines the deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the application.

The CRL may require additional clinical or other data, additional pivotal Phase 3 clinical trial(s) and/or other significant and time- consuming requirements related to clinical trials, preclinical studies or manufacturing.

If a CRL is issued, the applicant may either resubmit the NDA or BLA addressing all of the deficiencies identified in the letter or withdraw the application.

If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA or BLA, the FDA will issue an approval letter.

The FDA has committed to reviewing such resubmissions in response to an issued CRL in either two or six months depending on the type of information included.

Even with the submission of this additional information, however, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

If a product receives regulatory approval from the FDA, the approval is limited to the conditions of use (e.g., patient population, indication) described in the FDA-approved labeling.

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We expect to rely on a delivery system, such as pre-filled syringes, pen-injectors and/or autoinjectors to deliver certain of our product candidates.

Although we have not yet selected the delivery system to use for administration of such product candidates, including RLYB212 and RLYB116, we expect that, if approved, any such product candidate would be regulated as a combination product, because it is composed of both a drug or biological product and a delivery system “device.”

Although we have not yet selected the delivery system to use for administration of such product candidates, including RLYB116, we expect that, if approved, any such product candidate would be regulated as a combination product, because it is composed of both a drug or biological product and a delivery system “device.”

Under the FDCA and its implementing regulations, the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.

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A combination product with a drug or biologic primary mode of action would be reviewed and approved pursuant to the drug or biologic approval processes.

In reviewing the NDA or

BLA for such a product, however, the FDA review division reviewing the application could consult with their counterparts in the device center to ensure that the device component of the combination product met applicable requirements regarding safety, effectiveness, durability and performance.

Approval may require the performance of certain clinical studies, such as clinical usability or human factors studies to demonstrate the safety and/or effectiveness of the device component of the combination product.

In reviewing the NDA or BLA for such a product, however, the FDA review division reviewing the application could consult with their counterparts in the device center to ensure that the device component of the combination product met applicable requirements regarding safety, effectiveness, durability and performance.

Approval may require the

performance of certain clinical studies, such as clinical usability or human factors studies to demonstrate the safety and/or effectiveness of the device component of the combination product.

Similar considerations apply to regulation of drugs combined with delivery systems outside the United States, including in the EU.

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The FDA determines at the time that the marketing application is submitted, on a case-by-case basis, whether the proposed drug or biologic qualifies for priority review.

Significant improvement over available therapies may be illustrated, for example, by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting drug reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, or evidence of safety and effectiveness in a new subpopulation.

A priority review designation is intended to direct overall attention and resources to the evaluation of such applications and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months for an original BLA or NDA from the date of filing.

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The FDA may also grant accelerated approval for such a condition when the product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality ("IMM") and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

granted accelerated approval, FDA generally requires sponsors to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the product’s clinical benefit.

For drugs granted accelerated approval, FDA generally requires sponsors to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the product’s clinical benefit.

Failure to conduct required post-approval studies with due diligence, failure to confirm a clinical benefit during the post-approval studies, or dissemination of false or misleading promotional materials would allow the FDA to withdraw the product approval on an expedited basis.

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Post-approval Requirements

Following approval of a new product, the manufacturer and the approved product are subject to pervasive and continuing regulation by the FDA, governing, among other things, monitoring and recordkeeping activities, reporting of adverse experiences with the product and product problems to the FDA, product sampling and distribution, manufacturing and promotion and advertising.

reporting of adverse experiences with the product and product problems to the FDA, product sampling and distribution, manufacturing and promotion and advertising.

Although physicians may prescribe legally available products for unapproved uses or patient populations (i.e., “off-label uses”), manufacturers may not market or promote such uses.

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Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.

FDA regulations require that drug and biological products be manufactured in specific approved facilities and in accordance with cGMPs.

FDA regulations require that drug and biological products be manufactured in specific approved facilities and in accordance with cGMP.

The cGMP regulations include requirements relating to organization of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports and returned or salvaged products.

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In addition, for any of our product candidates that include a device delivery system, the device component will be subject to aspects of the Quality System Regulation ("QSR") applicable to medical devices.

Manufacturers of drug-device combination products may either opt to comply with all quality regulations governing each component of the product separately, or may take a “streamlined approach” to cGMP that allows the manufacturer to demonstrate compliance with the drug cGMPs along with compliance with several specific provisions from the device QSR—namely, management responsibility, design controls, purchasing controls, corrective and preventive action, installation, and servicing, as applicable.

Manufacturers of drug-device combination products may either opt to comply with all quality regulations governing each component of the product separately, or may take a “streamlined approach” to cGMP that allows the manufacturer to demonstrate compliance with the drug cGMP along with compliance with several specific provisions from the device QSR—namely, management responsibility, design controls, purchasing controls, corrective and preventive action, installation, and servicing, as applicable.

We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our products in accordance with cGMP regulations.

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Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance.

Future inspections by the FDA and other regulatory agencies may identify compliance issues at the facilities of our CMOs that may disrupt production or distribution or require substantial resources to correct.

In addition, the discovery of conditions that violate these rules, including failure to conform to cGMPs, could result in enforcement actions, and the discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or holder of an approved NDA or BLA, including voluntary recall and regulatory sanctions as described below.

Once an approval of a drug/biologic product is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.

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The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to gain approval of an NDA for a new chemical entity.

A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.

During the exclusivity period, the FDA may not accept for review an abbreviated new drug application ("ANDA") or a 505(b)(2) NDA submitted by another company for another version of such drug.

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Three-year exclusivity will not delay the submission or approval of a full NDA.

However, an applicant submitting a full NDA

would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

In addition, both drugs and biologics can obtain pediatric exclusivity in the United States.

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Under the BPCIA, a manufacturer may submit an application that is “biosimilar to” or “interchangeable with” a previously approved biological product or “reference product.” In order for the FDA to approve a biosimilar product, it must find that there are no clinically meaningful differences between the reference product and proposed biosimilar product in terms of safety, purity and potency.

For the FDA to approve a biosimilar product as interchangeable with a reference product, the agency must find that the biosimilar product can be expected to produce the same clinical results as the reference product and (for products administered multiple times) that the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

For the FDA to approve a biosimilar product

as interchangeable with a reference product, the agency must find that the biosimilar product can be expected to produce the same clinical results as the reference product and (for products administered multiple times) that the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

Upon licensure by the FDA, an interchangeable biosimilar may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.

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Orphan drug designation qualifies a company for certain tax credits.

In addition, if a product candidate that has orphan drug designation subsequently receives the first FDA approval for that drug for the disease for which it

has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same indication for seven years following product approval unless the subsequent product candidate is demonstrated to be clinically superior.

In addition, if a product candidate that has orphan drug designation subsequently receives the first FDA approval for that drug for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same indication for seven years following product approval unless the subsequent product candidate is demonstrated to be clinically superior.

Absent a showing of clinical superiority, the FDA cannot approve the same product made by another manufacturer for the same indication during the market exclusivity period unless it has the consent of the sponsor or the sponsor is unable to provide sufficient quantities.

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If a product designated as an orphan drug ultimately receives marketing approval for an indication broader than what was designated in its orphan drug application, it may not be entitled to exclusivity.

RLYB211 and RLYB212 have each been granted orphan drug designation by the FDA for the prevention of FNAIT.

RLYB212 has been granted orphan drug designation by the FDA for the prevention of FNAIT.

Rare Pediatric Disease Designation and Priority Review Vouchers

In 2012, Congress enacted the Food and Drug Administration Safety and Innovation Act requiring the FDA to award priority review vouchers to sponsors of certain rare pediatric disease product applications.

This program is designed to encourage development of new drug and biological products for prevention and treatment of “rare pediatric diseases” by, upon initial approval of an application meeting certain specified criteria, providing companies with a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product.

application for a different product.

The sponsor of a rare pediatric disease drug product receiving a priority review voucher may sell or otherwise transfer the voucher to another company.

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In addition to receiving rare pediatric disease designation, in order to receive a rare pediatric disease priority review voucher, the NDA or BLA must be given priority review, rely on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population, not seek approval for a different adult indication in the original rare pediatric disease product application and be for a drug that does not include a previously approved active ingredient.

In addition, under current statutory sunset provisions, even if a marketing application meets all of these requirements, FDA may only award a voucher prior to September 30, 2026 and only if the approved product received rare pediatric disease drug product designation prior to September 30, 2024.

RLYB211 and RLYB212 have each been granted rare pediatric disease designation by the FDA.

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Unless an exemption applies, diagnostic tests require marketing clearance via 510(k) notification or approval via Premarket Approval (“PMA”) application from the FDA prior to commercial distribution.

In August 2014, the FDA issued final guidance clarifying the requirements that will apply to approval of therapeutic products and in vitro companion diagnostics.

According to the guidance, for novel drugs and biologics, a companion diagnostic device and its corresponding therapeutic should be approved or cleared contemporaneously by the FDA for the use indicated in the therapeutic product’s labeling.

Approval or clearance of the companion diagnostic device will ensure that the device has been adequately evaluated and has adequate performance characteristics in the intended population.

In July 2016, the FDA issued a draft guidance intended to assist sponsors of the therapeutic products and in vitro companion diagnostic devices on issues related to co-development of the products.

For novel drugs and biologics, a companion diagnostic device and its corresponding therapeutic must be approved or cleared contemporaneously by the FDA for the use indicated in the therapeutic product’s labeling.

The FDA previously has required in vitro companion diagnostics intended to select the patients who will respond to a product candidate to obtain PMA simultaneously with approval of the therapeutic product candidate.

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Medical devices may be marketed only for the uses and indications for which they are cleared or approved.

Device manufacturers must also establish registration and device listings with the FDA.

In the United States, device manufacturers are also subject to FDA’s medical device reporting regulations, which require that a manufacturer report to the FDA if a device it markets may have caused or contributed to a death or serious injury, or has malfunctioned and the device or a similar device that it markets would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur, and FDA’s correction and removal reporting regulations, which require that manufacturers report to the FDA corrections or removals if undertaken to reduce a risk to health posed by the device or to remedy a violation of the FDCA that may present a risk to health.

manufacturers must also maintain establishment registration and device listings with the FDA.

In addition, device manufacturers are subject to FDA’s medical device reporting regulations, which require that a manufacturer report certain adverse events and device malfunctions to the FDA, and FDA’s correction and removal reporting regulations, which require that manufacturers report to the FDA corrections or removals if undertaken to reduce a risk to health posed by the device or to remedy a violation of the FDCA that may present a risk to health.

A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which covers the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging, and shipping of medical devices.

Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.

The FDA also may inspect foreign facilities that export products to the United States.

Device manufacturers are also subject to inspection by the FDA.

Regulation Outside of the United States

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our products outside of the United States.

Whether or not we obtain FDA approval for a product candidate, we must obtain approval by the comparable regulatory authorities of foreign countries or economic areas, such as the 27-EU member states, before we may commence clinical trials or market products in those countries or areas.

Immediately following the UK's departure from the EU, in Great Britain (being England, Wales and Scotland), all medicinal products with a centralized EU marketing authorization were automatically converted to Great Britain marketing authorizations unless marketing authorization holders opted out of this process.

According to Article 5(4) of Annex 2 to the Northern Ireland Protocol contained in the Agreement on the withdrawal of the UK

from the EU and the European Atomic Energy Community, c entralized marketing authorizations continue to apply in Northern Ireland.

The post-Brexit restrictions on movements of goods including medicines have now been corrected by the “Windsor Framework”.

Following the so-called “Windsor Framework” which is a political declaration by the European Commission and the Government of the UK of February 27 2023, from January 1 2025, all new medicines for the UK market, including Northern Ireland, will be authorized by the MHRA and UK packaging must carry a clearly legible ‘UK only’ to be allowed onto the UK market.

For three years from January 1, 2021, the MHRA, the UK medicines regulator, may rely on a European Commission marketing authorization approval in the centralized procedure, i.e., the EC Decision Reliance Procedure (“ECDRP”), in order to expedite an application for a Great Britain marketing authorization.

A separate application is still required, and marketing authorizations are granted by the MHRA.

From January 1, 2024, the ECDRP was replaced by the new International Recognition Procedure (“IRP”).

IRP is open to applicants that have already received an authorization for the same product from one of the MHRA’s specified reference regulators.

IRP allows the MHRA to take into account the expertise and decision-making of trusted regulatory authorities to conduct targeted assessments of IRP applications while retaining the authority to reject applications if the evidence provided is considered insufficiently robust.

The EU and the UK have concluded a trade and cooperation agreement (“TCA”), which was provisionally applicable from January 1, 2021 and has been formally applicable since May 1, 2021.

The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of the outcomes of good manufacturing practice (“GMP”) inspections and applicants and marketing authorization holders may submit GMP certificates issued by the MHRA for sites located outside the EU/European Economic Area (“EEA”) as supporting information for EU regulatory submissions.

However, the TCA does not foresee wholesale mutual recognition of UK and EU pharmaceutical regulations.

Great Britain has also implemented EU legislation on the marketing, promotion and sale of medicinal products through the Human Medicines Regulations 2012 (as amended) (under the Northern Ireland Protocol, the EU regulatory framework will continue to apply in Northern Ireland, which is the subject of ongoing negotiation between the UK Government and the European Commission).

The regulatory regime in Great Britain currently broadly aligns with EU regulations.

However, it is possible that these regimes may diverge in the future.

It remains to be seen how Brexit will impact regulatory requirements for product candidates and products in the UK in the long-term.

With the exception of the EU EEA applying the harmonized regulatory rules for medicinal products, the approval process and requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly between countries and jurisdictions and can involve additional testing and additional administrative review periods.

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our products.

Whether or not we obtain FDA approval for a product candidate, we must obtain approval from the comparable regulatory authorities of foreign countries or economic areas, such as the EU, before we may commence clinical trials or market products in those countries or areas.

Until recently, the EMA and the European Commission ("EC") were responsible for approving new medicines for supply in Northern Ireland according to the Northern Ireland Protocol.

From January 1, 2025, in accordance with the “Windsor Framework,” all new medicines for the UK market, including Northern Ireland, will be authorized by the MHRA and UK packaging must carry a clearly legible ‘UK only’ to be allowed onto the UK market.

The International Recognition Procedure provides the framework for the MHRA to take into account assessments of medicinal products conducted by trusted regulatory authorities in Australia, Canada, Switzerland, Singapore, Japan, the United States and the EU when assessing applications for marketing authorization.

With the exception of the EU EEA applying harmonized regulatory rules for medicinal products, the approval process and requirements governing the conduct of clinical trials, product licensing, and pricing and reimbursement vary greatly between countries and jurisdictions and can involve additional testing and additional administrative review periods.

The time required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval.

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European Union Drug Development, Review and Approval

In the EU, our product candidates will also be subject to extensive regulatory requirements.

As in the United States, medicinal products can be marketed only if a marketing authorization is granted by a competent regulatory agency.

In the EU, our product candidates will be subject to extensive regulatory requirements.

As in the United States, medicinal products can be marketed only if a marketing authorization ("MA") is granted by a competent regulatory agency.

Similar to the United States, the various phases of preclinical and clinical research in the EU are subject to significant regulatory controls.

The old regime, the EU Clinical Trials Directive 2001/20/EC (the “CTD”) has now been repealed and replaced by a new legislative framework provided by Regulation (EU) No 536/2014 (the “CTR”).

As of January 31, 2022, the CTR, came into application, and with it, the launch of the Clinical Trials Information System (“CTIS”), the centralized EU portal and database for clinical trials.

The CTR is directly applicable in all EU Member States (and so does not require national implementing legislation in each EU Member State to give effect to the EU law instrument).

The CTR has simplified the approval process for clinical trials to be carried out in the EU.

Rather than applying for a clinical trial authorization in each EU Member State where the trial will be conducted, the CTR provides that one application be submitted centrally, via CTIS, which will then be reviewed by the designated NCA.

If successful, the resulting decision arising from the evaluation process would cover all EU Member States concerned by the application.

From January 31, 2023 all submissions of initial CTA applications for a new clinical trial must be made via CTIS.

By January 31, 2025, all ongoing trials approved under the CTD must comply with the CTR and information relating to such clinical trials must be recorded in CTIS.

For any of our product candidates that incorporate a medical device to administer the medicinal product and are intended to be commercialized as a single integral product intended exclusively for use in the given combination and not usable separately, then the combination product is regulated by Directive 2001/83/EC or Regulation (EC) 726/2004 as a medicinal product.

However, the medical device used for administration must satisfy the requirements for its general safety and performance under EU law governing general medical devices.

The EU regulatory regime currently provided under Directive 93/42/EEC (the "Medical Devices Directive") will be replaced by Regulation (EU) 2017/745 on medical devices (the "Medical Devices Regulation").

The Medical Devices Regulation came into application on May 26, 2021, subject to the transitional provisions for certain medical devices to remain on the EU market if they were certified under the Medical Devices Directive for a limited period.

There are significant changes to the EU regulatory system governing medical devices under the Medical Devices Regulation.

Under the Medical Devices Regulation, data relating to the general safety and performance of the medical device must be contained in an application for marketing authorization for the combination product.

Such information must be provided by the manufacturer of the medical device in its EU declaration of conformity or the relevant certificate issued by a notified body allowing the medical device manufacturer to affix a European Conformity (“CE”) mark to the medical device.

If the dossier submitted to support the marketing authorization does not include the results of the conformity assessment or a CE certificate and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with the Medical Devices Regulation, the medicinal products authority such as the EMA responsible for assessing applications for marketing authorization via the centralized procedure can require the applicant for a marketing authorization to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements issued by a designated notified body.

By May 26, 2024, all manufacturers must comply with the Medical Devices Regulation.

However, the EU legislature has extended the transitional periods, depending upon the risk classification of the medical device, e.g.

December 31, 2027 for Class III devices and Class IIb implantable devices.

Under the EU regulatory regime, a company may submit marketing authorization applications under a centralized, decentralized or mutual recognition procedure.

Where the product is intended to be marketed in one EU member state, a national application for a marketing authorization is filed.

The centralized procedure is compulsory for medicinal products produced by biotechnology, designated orphan medicines, advanced-therapy medicines such as gene-therapies, and those medicinal products containing new active substances for specific indications such as the treatment of HIV, AIDS and immune dysfunctions, cancer, neurodegenerative diseases, diabetes, and viral diseases, and is optional for other medicines, which are highly innovative.

In the EU, clinical trials are primarily regulated by Regulation (EU) No 536/2014 (the “CTR”).

The CTR requires sponsors to submit one clinical trial authorization (“CTA”) application via the Clinical Trials Information System, which will then be reviewed by the competent regulatory agency selected by the sponsor to lead the validation and evaluation of the application.

If successful, the resulting CTA would cover all EU Member States concerned by the application.

However, a concerned Member State may in limited circumstances declare an “opt-out” from an approval and prevent the clinical trial from being conducted in such Member State.

In addition to a CTA, sponsors of clinical trials conducted in the EU must also obtain a positive opinion on the clinical trial from a research ethics committee in each Member State where the trial will be conducted.

Combination Products

Product candidates that incorporate a medical device for the administration of the medicinal product, and which are intended to be commercialized as a single integral product used exclusively in the given combination, will be regulated by Directive 2001/83/EC or Regulation (EC) 726/2004 as a medicinal product.

However, the medical device component must satisfy the general safety and performance requirements under applicable EU law governing general medical devices.

Proof of such must be included in an application for MA for the combination product.

In particular, to the extent the device component has already been conformity assessed and a European Conformity (“CE”) mark affixed, the certificate of conformity issued by the Notified Body must be provided in the MA application dossier.

Where the medical device component has not already been CE marked, the MA application dossier must include an opinion issued by a notified body on the conformity of the device

component against the relevant general safety and performance requirements set out in Annex I of Regulation (EU) 2017/745.

EU regulatory regime contemplates that MAs can be granted either centrally or nationally, albeit through mutual recognition or decentralized procedure.

Centralized Procedure

Under the centralized procedure, a single marketing authorization application is submitted to the EMA where it will be evaluated by its advisory committee, the Committee for Medicinal Products for Human Use (the “CHMP”).

A favorable CHMP opinion results in a single marketing authorization granted by the European Commission in an implementing decision, known as a centralized marketing authorization.

A centralized marketing authorization is valid for all EU member states and, by extension (after taking the corresponding national implementing measures), in Norway, Iceland and Liechtenstein.

In general, the initial marketing authorization is valid for five years, but once renewed is usually valid for an unlimited period, unless the European Commission decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal.

Under the centralized procedure, the maximum timeframe for the evaluation of a marketing authorization application by the EMA is 210 days, excluding clock stops.

The centralized procedure is compulsory for:

medicinal products produced by biotechnology;

orphan medicinal products;

advanced-therapy medicinal products such as gene-therapies;

and medicinal products containing new active substances and which are indicated for the treatment of HIV, AIDS and immune dysfunctions, cancer, neurodegenerative diseases, diabetes, autoimmune and other immune dysfunctions, and viral diseases.

The centralized procedure is optional for other medicines containing a new active substance, which constitute a significant therapeutic, scientific or technical innovation, or which are in the interest of public health in the EU.

Under the centralized procedure, a single MA application is submitted to the EMA where it will be evaluated by its advisory committee, the Committee for Medicinal Products for Human Use (the “CHMP”).

Under the centralized procedure, the maximum timeframe for the evaluation of a MA application by the EMA is 210 days, excluding clock stops.

Clock-stops allow the applicant the necessary time to provide additional information in response to questions raised by the CHMP.

The clock-stops considerably extend the time taken by the CHMP to complete the evaluation of a marketing authorization application.

Ordinarily, within 67 days of receipt of the positive scientific opinion provided by the EMA, the European Commission will issue a binding decision on granting of a centralized marketing authorization.

The clock-stops considerably extend the time taken by the CHMP to complete the evaluation of a MA application.

The EMA will then provide the EC with an opinion on whether the medicinal product should be approved.

Ordinarily, within 67 days of receipt of a positive scientific opinion from the EMA, the EC will adopt single MA an implementing decision on granting a centralized marketing authorization.

A centralized MA is valid for all EU member states and, by extension (after taking the corresponding national implementing measures), in Norway, Iceland and Liechtenstein.

National Procedure

The purely national procedure results in a MA in a single EU Member State.

This route is available for products not falling within the mandatory scope of the centralized procedure.

Decentralized Procedure

The decentralized procedure allows marketing authorization application in respect of medicinal products not authorized in the EU/EEA to be submitted simultaneously in two or more EU member states, whereas the

mutual recognition procedure must be used if the product has been authorized in at least one EU member state on a national basis, and the applicant seeks approval progressively of the same medicinal product in one or more EU member state(s).

The decentralized procedure allows national MA applications in respect of medicinal products not authorized in the EU/European Economic Area ("EEA") to be submitted simultaneously in multiple EU member states.

This is in contrast to the mutual recognition procedure, which applies if the product has been authorized in at least one EU member state on a national basis, and the applicant seeks approval progressively of the same medicinal product in one or more EU member state(s).

Both the decentralized and mutual recognition procedures provide for approval by one or more “concerned” member state(s) based on an assessment of an application performed by one “reference” member state.

Under the decentralized approval procedure, an applicant submits an application, accompanied by a dossier, containing the requisite scientific data, and related materials to the reference member state and concerned member state(s).

Under the decentralized procedure, an applicant submits an application, accompanied by a dossier, containing the requisite scientific data, and related materials to the reference member state and concerned member state(s).

The reference member state prepares a draft assessment and drafts of the related materials within 120 days of the receipt of a valid application.

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Mutual Recognition Procedure

Under the mutual recognition procedure, the concerned member state(s) have a 90-day period to recognize the marketing authorization in the reference member state.

Under the mutual recognition procedure, the concerned member state(s) have a 90-day period to recognize the MA in the reference member state.

The decentralized procedure contemplates a single clock-stop at day 105 for applicants to address questions raised by the reference member state and concerned member states, which may extend the process for completing the assessment procedure.

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If this is not possible, the reference member state can escalate the issue to the EMA for arbitration.

The purely national procedure results in a marketing authorization in a single EU member state.

Conditional Marketing Authorization

In specific circumstances, E.U.

legislation (Article 14–a Regulation (EC) No 726/2004 (as amended by Regulation (EU) 2019/5) and Commission Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables applicants to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.

In specific circumstances, Regulation (EC) No 726/2004 (as amended) enables applicants to obtain a conditional MA prior to obtaining the comprehensive clinical data required for an application for a full MA.

Such conditional approvals may be granted for product candidates (including medicines designated as orphan medicinal products) if (1) the product candidate is intended for the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases;

(2) the drug candidate is intended to meet unmet medical needs of patients;

(3) a marketing authorization may be granted prior to submission of comprehensive clinical data provided that the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required;

(2) the drug candidate is intended to meet unmet medical

needs of patients;

(3) a MA may be granted prior to submission of comprehensive clinical data provided that the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required;

(4) the risk-benefit balance of the product candidate is positive, and (5) it is likely that the applicant will be in a position to provide the required comprehensive clinical trial data.

A conditional marketing authorization requires specific obligations to be fulfilled by the marketing authorization holder, including obligations with respect to the completion of ongoing or new studies and with respect to the collection of pharmacovigilance data.

Conditional marketing authorizations are valid for one year, and can be renewed annually, if the risk-benefit balance remains positive, and after a satisfactory assessment of benefit:

A conditional MA requires specific obligations to be fulfilled by the MA holder, including obligations with respect to the completion of ongoing or new studies and with respect to the collection of pharmacovigilance data.

Conditional MAs are valid for one year, and can be renewed annually, if the risk-benefit balance remains positive, and after a satisfactory assessment of benefit:

risk balance and progress in fulfilling the specific obligations.

The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional marketing authorization.

The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional MA.

Pediatric Studies

In the EEA, companies developing a new medicinal product must agree upon a pediatric investigation plan (“PIP”), with the EMA’s Pediatric Committee (“PDCO”) and must conduct pediatric clinical trials in accordance with that PIP, unless a waiver applies.

The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the drug for which a marketing authorization is being sought.

The PIP sets out the timing and measures proposed for the generation of data to support a pediatric indication of the drug for which a MA is being sought.

The PDCO can grant a deferral of the obligation to implement some or all of the measures of the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults or other age groups not covered by the agreed PIP.

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or the disease or condition occurs only in adult populations, or the specific medicinal product does not represent a significant therapeutic benefit over existing treatments in pediatric patients.

Products that are granted a marketing authorization with the results of the pediatric clinical trials conducted in accordance with the PIP (even where such results are negative) are eligible for six months’ supplementary protection certificate extension.

Products that are granted a MA with the results of the pediatric clinical trials conducted in accordance with the PIP (even where such results are negative) are eligible for a six month extension to their supplementary protection certificate.

In the case of orphan medicinal products, a two-year extension of the orphan market exclusivity may be available.

This pediatric reward is subject to the condition that the results are provided in respect of all studies in compliance with the agreed PIP and is not automatically available.

This pediatric reward is subject to the condition that the results are provided in respect of all studies in compliance with the agreed PIP.

European Union Regulatory Data Exclusivity

In the EU, new products, which are considered as referenced medicinal products, authorized for marketing qualify for eight years of data exclusivity and an additional two years of marketing exclusivity upon grants of a marketing authorization.

The data exclusivity period prevents generic or biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the EU during a period of eight years from the date on which the reference product was first authorized in the EU.

The marketing exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until ten years have elapsed from the initial authorization of the reference medicinal product in the EU.

The ten-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

In the EU, new products containing a new active substance (so called “reference medicinal products”) qualify for eight years of data exclusivity and an additional two years of marketing exclusivity upon grants of a MA.

The data exclusivity period prevents generic or biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference medicinal product when applying for a generic or biosimilar MA in the EU.

The marketing exclusivity period prevents a successful generic or biosimilar MA applicant from commercializing its product in the EU until ten years have elapsed from the initial authorization of the reference medicinal product in the EU.

The ten-year market exclusivity period can be extended to a maximum of eleven years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

European Union Orphan Designation and Exclusivity

The criteria for designating an orphan medicinal product in the EU are similar in principle to those in the United States.

Under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life- threatening or chronically debilitating condition, (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.

Under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as orphan if it is intended for the diagnosis, prevention or treatment of a life- threatening or chronically debilitating condition, which either (a) affects not more than five in 10,000 persons in the EU when the application is made, or (b) , without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment.

In each case, there can exist no satisfactory method of diagnosis, prevention or treatment of such condition authorized in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.

The term ‘significant benefit’ is defined in Regulation (EC) 847/2000 to mean a clinically relevant advantage or a major contribution to patient care.

Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers and are, upon grant of a marketing authorization, entitled to ten years of market exclusivity for the approved therapeutic indication.

During this ten-year market exclusivity period, the EMA or the competent authorities of the Member States of the EEA, cannot accept an application for a marketing authorization for a similar medicinal product for the same indication.

Orphan medicinal products are upon grant of a MA, entitled to ten years of market exclusivity for the approved therapeutic indication.

During this ten-year market exclusivity period, the EMA or the competent authorities of the Member States of the EEA, cannot accept an application for a MA for a similar medicinal product for the same indication.

A similar medicinal product is defined as a medicinal product containing a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic indication.

The application for orphan designation must be submitted before the application for marketing authorization.

The applicant will receive a fee reduction for the marketing authorization application if the orphan designation has been granted, but not if the designation is still pending at the time the marketing authorization is submitted.

The application for orphan designation must be submitted before the application for MA.

The applicant will receive a fee reduction for the MA application if the orphan designation has been granted, but not if the designation is still pending at the time the MA is submitted.

Orphan designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

The ten-year market exclusivity in the EU may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity.

Additionally, marketing authorization may be granted to a similar product for the same indication at any time if:

Additionally, MA may be granted to a similar product for the same indication at any time if:

• the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior;

• the applicant consents to a second orphan medicinal product application;

• the applicant cannot supply enough orphan medicinal product.

Orphan drug designation must be requested before submitting an application for marketing approval.

Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

• the applicant cannot supply enough of the orphan medicinal product.

An equivalent regime is reflected in domestic law in the UK.

Under the UK regime, however, orphan designations are not granted and instead a decision is made at the point of marketing authorization grant.

RLYB211 and RLYB212 have each been granted orphan drug designation by the EMA for the prevention of FNAIT.

RLYB212 has been granted orphan drug designation by the EMA for the prevention of FNAIT.

Priority Medicines Designation

The EMA grants access to the Priority Medicines ("PRIME") program to investigational medicines for which it determines there to be preliminary data available showing the potential to address an unmet medical need and bring a major therapeutic advantage to patients.

Developers of innovative medicinal product can apply to the EMA for access to the Priority Medicines ("PRIME") program.

A medicinal product will be accepted onto the PRIME scheme if the EMA determines that the available preliminary data demonstrate the medicinal product’s potential to address an unmet medical need and bring a major therapeutic advantage to patients.

As part of the program, EMA provides early and enhanced dialogue and support to optimize the development of eligible medicines and speed up their evaluation, aiming to bring promising treatments to patients sooner.

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Periods of Authorization and Renewals

A marketing authorization is valid for five years in principle and the marketing authorization may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the authorizing member state.

To this end, the marketing authorization holder must provide the EMA or the competent authority with a consolidated version of the file in respect of quality, safety and efficacy, including all variations introduced since the marketing authorization was granted, at least nine months before the marketing authorization ceases to be valid.

Once renewed, the marketing authorization is generally valid for an unlimited period, unless the European Commission or the competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal.

Any authorization which is not followed by the actual placing of the drug on the EU market (in case of centralized procedure) or on the market of the authorizing member state within three years after authorization ceases to be valid (the so-called sunset clause).

In general, an initial MA is valid for five years and may be renewed on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the authorizing member state.

To this end, the MA holder must provide the EMA or the competent authority with a consolidated version of the file in respect of the medicinal product’s quality, safety and efficacy, including all variations introduced since the MA was granted, at least nine months before the MA ceases to be valid.

Once renewed, the MA is generally valid for an unlimited period, unless the European Commission or the competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal.

In accordance with the sunset clause, any authorization which is not followed by the actual placing of the drug on the EU market (in case of centralized procedure) or on the market of the authorizing member state (in the case of the national, decentralized and mutual recognition procedures) within three years after the MA is granted will cease to be valid.

Brexit and the Regulatory Framework in the United Kingdom

The UK formally left the EU on January 31, 2020, and after the expiry of the transition period on December 31, 2020, became a “third country” for the purposes of EU law.

At present, the regulatory regime in the UK broadly aligns with EU regulations.

However, it is possible that the regime may diverge in the future.

It remains to be seen how Brexit will impact regulatory requirements for product candidates and products in the UK in the long-term.

The EU and the UK concluded a trade and cooperation agreement (“TCA”), which was applied provisionally from January 1, 2021 and entered into force on May 1, 2021.

The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of the outcomes of GMP inspections and GMP documents.

However, the TCA does not foresee wholesale mutual recognition of UK and EU pharmaceutical regulations.

Rest of the World Regulation

For other countries outside of the EU and the United States, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from jurisdiction to jurisdiction.

Additionally, the clinical trials must be conducted in accordance with cGCP requirements and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

Additionally, the clinical trials must be conducted in accordance with current good clinical practice requirements and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions, and criminal prosecution.

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Significant uncertainty exists regarding coverage and reimbursement for newly approved healthcare products.

Coverage does not ensure adequate reimbursement.

It is time consuming and expensive to seek coverage and reimbursement from third-party payors.

We may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain FDA regulatory approvals.

Seeking coverage and reimbursement is time consuming and expensive.

We may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and cost-effectiveness of our products, which would be in addition to the studies required to obtain FDA regulatory approvals.

Third-party payors may take into account clinical practice guidelines in determining coverage and there may be significant delays before our products are addressed by such guidelines and we cannot predict what position such guidelines would take with respect to our products if and when addressed.

Coverage and reimbursement varies across third-party payors.

Third-party payors may limit coverage to specific products on an approved list, or formulary, which might not include all of the approved products for a particular indication, or utilize other mechanisms to manage utilization (such as requiring prior authorization for coverage for a product for use in a particular patient).

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Regulation (EU) 2021/2282 on health technology assessment (the “HTA Regulation”) entered into force on January 11, 2022 and will apply from January 12, 2025.

Given the increasing use of health technology assessment (“HTA”) to guide market access in EU member states, the HTA Regulation seeks to achieve three legislative objectives:

Given the increasing use of HTA to guide market access in EU member states, the HTA Regulation seeks to achieve three legislative objectives:

to promote convergence in HTA tools, procedures and methodologies;

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From January 15, 2025, all new oncology medicines and advanced therapy medicinal products (i.e.

gene and cell therapies and tissue engineered products) will be assessed at EU level through the Joint Clinical Assessment procedure (“JCA”), which is part of an HTA to evaluate the relative clinical effectiveness of a new health technology against one or more other health technologies.

gene and cell therapies and tissue engineered products) will be assessed at EU level through the Joint Clinical Assessment procedure (“JCA”), which forms part of an HTA and evaluates the relative clinical effectiveness of a new health technology against one or more other health technologies.

Importantly, the outcomes of JCAs are not binding on national HTA bodies which may draw their own conclusions on the clinical added value of a new technology.

From January 13, 2028, all new orphan medicinal products will be subject to JCA.

From January 13, 2030, all new medicines will come under the scope of the HTA Regulation.

The HTA Regulation established the Coordination Group on HTA (the “HTACG”) consisting of representatives of EU member states, mainly from HTA authorities or bodies.

The HTA Regulation established the Coordination Group on

HTA (the “HTACG”) consisting of representatives of EU member states, mainly from HTA authorities or bodies.

The HTACG’s remit is to coordinate and adopt the joint HTA work carried out by its subgroups within the scope of the HTA Regulation and to adopt methodological and procedural guidance documents for joint work, including JCAs.

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• FDCA, which among other things, strictly regulates drug marketing, prohibits manufacturers from marketing such products prior to approval or for off-label use and regulates the distribution of samples;

• federal laws that require pharmaceutical manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs;

• federal laws that require pharmaceutical manufacturers to calculate, report and certify certain complex product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under government healthcare programs;

• federal Open Payments (or federal “sunshine” law), which requires pharmaceutical and medical device companies to monitor and report certain financial interactions with certain healthcare providers to the Centers for Medicare & Medicaid Services within the U.S.

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state laws requiring pharmaceutical companies to comply with specific compliance standards, restrict financial interactions between pharmaceutical companies and healthcare providers or report information related to payments to health care providers, marketing expenditures or drug prices;

state laws regulating the manufacture and distribution of biopharmaceutical products;

and state laws governing privacy, security and breaches of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts;

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In particular, government authorities and other third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medical products and services.

Health care reform, specifically reform addressing pricing and payment for drugs, was a focus of the Trump administration and remains a focus of the Biden administration.

Health care reform, specifically reform addressing pricing and payment for drugs, has been an ongoing focus and is likely to continue under the Trump Administration.

A number of healthcare reforms involving drugs have been successfully implemented, including reforms related to Medicare payment for drugs and manufacturer rebate obligations under the Medicaid Drug Rebate Program.

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state data privacy laws.

In 2018, California passed into law the California Consumer Privacy Act which took effect on January 1, 2020 and was expanded by the California Privacy Rights Act, which took effect on January 1, 2023, and which, collectively, imposed many requirements on businesses that process the personal information of California residents (collectively, “CCPA”).

Many of the CCPA’s requirements are similar to those found in the General Data Protection Regulation (the "GDPR"), including requiring businesses to provide notice to data subjects regarding the personal information collected about them and how such information is used, shared, and retained, requiring that use, retention and sharing of personal information be reasonably necessary and proportionate to the purposes of collection or processing, providing data subjects the rights, in certain circumstances, to (i) request access to such personal information;

(ii) request the erasure of such personal information;

(iii) opt-out of “sales” of their personal information, (iv) opt-out of the “sharing” of their personal information ( i.e.

, disclosing for cross-context behavioral advertising), and (v) limit the use and disclosure of their “sensitive personal information” for purposes other than those for which it was collected.

The CCPA contains significant penalties for companies that violate its requirements.

It also provides California residents a private right of action, including the ability to seek statutory damages, in the event of a breach involving their personal information.

Compliance with the CCPA is a rigorous and time-intensive process.

Similar laws have been proposed or passed in more than half of the states in the United States and in the U.S.

For example, the California Consumer Privacy Act of 2018, as amended and supplemented by the California Privacy Rights Act (collectively, “CCPA”) imposed many requirements for the collection, processing, and sharing of personal information of California residents.

The CCPA contains significant penalties for companies that violate its requirements and provides California residents a private right of action, including the ability to seek statutory damages, in the event of a breach involving their personal information.

Similar omnibus privacy laws have been proposed or passed in more than half of the states in the United States and in the U.S.

Congress, reflecting a trend toward more stringent privacy legislation in the United States.

In addition, Washington state enacted the My Health, My Data Act, a health-focused consumer privacy law, which took effect in March 2024.

This law imposes obligations related to the collection and sharing of certain health-related information that is not subject to HIPAA and that does not fall within certain other exceptions in the law.

Other states have enacted, or are in the process of enacting, similar health-focused consumer privacy laws.

Also of note, in June 2024, the Protecting Americans’ Data from Foreign Adversaries Act of 2024 took effect.

This law prohibits data brokers from making available certain personally identifiable sensitive data of U.S.

individuals to “foreign adversary” countries, such as the People’s Republic of China (the “PRC”), and entities controlled by such countries.

Additionally, in January 2025, the U.S.

Department of Justice published a final rule implementing President Biden’s Executive Order 14117, “Preventing Access to Americans’ Bulk Sensitive Personal Data and United States Government-Related Data by Countries of Concern.” This final rule prohibits certain data brokerage transactions and transactions involving certain bulk human ‘omic data, including human genomic data and

biospecimens from which such data can be derived, with restricted persons and jurisdictions, such as the PRC.

The final rule also places restrictions on certain vendor, employment and investment agreements with such jurisdictions.

Most provisions of the final rule are scheduled to take effect in April 2025.

These restrictions may affect our ability to engage in collaborations or license agreements with entities in restricted countries or with a nexus to such countries going forward.

Compliance with evolving U.S.

privacy and security laws, requirements and regulations may result in cost increases due to necessary systems changes, new limitations or constraints on our business models and the development of new administrative processes.

General Data Protection Regulation

Many countries outside of the United States maintain rigorous laws governing the privacy and security of personal information.

For example, the collection, use, disclosure, transfer, or other processing of personal data, including personal health data, regarding individuals who are located in the EEA, and the processing of personal data that takes place in the EEA, is subject to the GDPR, which became effective on May 25, 2018.

The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, and it imposes heightened requirements on companies that process health and other sensitive data, such as requiring in many situations that a company obtain the consent of the individuals to whom the sensitive personal data relate before processing such data.

Examples of obligations imposed by the GDPR on companies processing personal data that fall within the scope of the GDPR include providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, appointing a data protection officer, providing notification of data breaches and taking certain measures when engaging third-party processors.

The GDPR also imposes strict rules on the transfer of personal data to countries outside the EEA, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million, or 4% of annual global revenues, whichever is greater.

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.

Compliance with the GDPR is a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance.

On June 4, 2021, the European Commission released two revised sets of standard contractual clauses, which have been designed in part to assist organizations in meeting the requirement of the CJEU’s judgment.

However, it is unclear how the use of these clauses will be scrutinized and enforced by supervisory authorities and privacy interest groups, and the process of entering into agreements with new standard contractual clauses, and updating our existing agreements that contain the previous clauses, may lead to additional costs and increase our overall risk exposure.

The GDPR permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million, or 4% of annual global revenues, whichever is greater, and confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.

Following the withdrawal of the U.K.

from the EU, the U.K.

Data Protection Act 2018 applies to the processing of personal data that takes place in the

Data Protection Act 2018 applies to the processing of personal data that takes place in the U.K.

and includes parallel obligations to those set forth by GDPR.

Other countries maintain different privacy laws that we are subject to which may further increase our costs of compliance and expose us to greater legal risk.

These laws and similar privacy laws enacted by other countries may further increase our costs of compliance and expose us to greater legal risk.

Employees and Human Capital Resources

Our employees are driven by our mission to identify and accelerate the development of transformative therapies for patients with rare disorders.

We believe that our deep commitment to high ethical and professional standards is fundamental to our mission, and we are determined to build a culture that values diversity, inclusiveness and equity, and empowers a skilled and experienced workforce to perform at the highest levels.

We believe that our deep commitment to high ethical and professional standards is fundamental to our mission, and we are determined to build a culture that empowers a skilled and experienced workforce to perform at the highest levels.

We commit our resources and make investments, including through recruiting, training and collaboration, to promote the culture that we desire, and we expect our employees to embrace the Company’s values and culture in all that we do.

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Corporate Information

Rallybio was founded in 2018.

Rallybio Holdings, LLC ("Rallybio Holdings") was formed in Delaware in March 2018 and Rallybio IPD, LLC was formed in Delaware in May 2020.

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Available Information

Our Internet address is www.rallybio.com.

Our Internet address is https://www.rallybio.com.

Our website and the information contained on, or that can be accessed through, the website will not be deemed to be incorporated by reference in, and are not considered part of, this Annual Report on Form 10-K.

Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including exhibits, proxy and information statements and amendments to those reports filed or furnished pursuant to Sections 13(a), 14, and 15(d) of the Securities Exchange Act of 1934, as amended (the "Exchange Act”) are available through the “Investors” portion of our website free of charge as soon as reasonably practicable after we electronically file such material with, or furnish it to, the Securities and Exchange Commission ("SEC").

In addition, our filings with the SEC may be accessed through the SEC’s Interactive Data Electronic Applications system at http://www.sec.gov.

In addition, our filings with the SEC may be accessed through the SEC’s

Interactive Data Electronic Applications system at https://www.sec.gov.

All statements made in any of our securities filings, including all forward-looking statements or information, are made as of the date of the document in which the statement is included, and we do not assume or undertake any obligation to update any of those statements or documents unless we are required to do so by law.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business