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Item 1. Business

2025-03-13 compared with 2024-03-07 · 237 added, 152 removed, 364 unchanged (52% of the section changed)

Our Corporate History and Background

The Company (formerly known as Selecta Biosciences, Inc., or Selecta) was incorporated in Delaware on December 10, 2007, and is headquartered in Gaithersburg, Maryland.

The Company (formerly known as Selecta Biosciences, Inc., or Selecta) was incorporated in Delaware on December 10, 2007, and is headquartered in Frederick, Maryland.

On November 13, 2023, the Company and the Delaware corporation which, immediately prior to the Merger (as defined below), was known as Cartesian Therapeutics, Inc., or Old Cartesian, entered into an Agreement and Plan of Merger, or the Merger Agreement, by and among the Company, Sakura Merger Sub I, Inc., a Delaware corporation and a wholly owned subsidiary of the Company, or First Merger Sub, Sakura Merger Sub II, LLC, a Delaware limited liability company and wholly owned subsidiary of the Company, or Second Merger Sub, and Old Cartesian.

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until immediately prior to the Merger) changed its corporate name to Cartesian Therapeutics, Inc.

We are a clinical-stage biotechnology company developing mRNA cell therapies for the treatment of autoimmune diseases.

We are a clinical-stage biotechnology company pioneering mRNA cell therapy for the treatment of autoimmune diseases.

We leverage our proprietary technology and manufacturing platform to introduce one or more mRNA molecules into cells to enhance their function.

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Therefore, our mRNA cell therapies are distinguished by their capacity to be dosed repeatedly like conventional drugs, administered in an outpatient setting, and given without pre-treatment chemotherapy required with many conventional cell therapies.

In an open-label Phase 2 clinical trial in patients with myasthenia gravis, or MG, a chronic autoimmune disease that causes disabling muscle weakness and fatigue, we observed that our lead product candidate, Descartes-08, generated a deep and durable clinical benefit.

In a placebo-controlled Phase 2b clinical trial in patients with myasthenia gravis, or MG, a chronic autoimmune disease that causes disabling muscle weakness and fatigue, we observed that our lead product candidate, Descartes-08, generated a deep and durable clinical benefit where we observed an average MG-ADL (Activities of Daily Living) reduction of 5.5 points at Month 4 with a third of patients achieving minimal symptom expression at Month 6 and 80% of participants reaching Month 12 maintained a clinically meaningful response.

Durability of response in MG is commonly measured over a period of 26 to 52 weeks, and maintenance of response over that period is considered durable.

Autoimmune diseases, where the immune system mistakenly attacks the body, are a family of more than 80 disorders.

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We believe there is a significant unmet need for outpatient treatments, completed over a short period of time, that provide deep, durable clinical benefit.

Cell therapies have the potential to provide this benefit, but conventional cell therapies that use DNA are associated with toxicities, including cytokine release syndrome, neurotoxicity, transformation to cancer, and death.

Cell therapies have the potential to provide this benefit, but conventional cell therapies that use DNA are associated with toxicities, including cytokine release syndrome, or CRS, neurotoxicity, transformation to cancer, and death.

Further, conventional cell therapies typically require pre-treatment with chemotherapy, which suppresses the immune system and increases the risk of infection, anemia, and neurotoxicity.

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We believe our mRNA cell therapies have the potential to deliver deep, durable clinical benefit to a broad group of patients with autoimmune diseases because they can be administered over a short period of time, in an outpatient setting, and without pre-treatment chemotherapy.

We are leveraging our proprietary technology and manufacturing platform, RNA Armory ® , to develop mRNA cell therapies for autoimmune diseases across three modalities.

We are leveraging our proprietary technology and manufacturing platform to develop mRNA cell therapies for autoimmune diseases.

Our mRNA CAR-T modality is a personalized approach that collects a patient’s T-cells and uses mRNA to introduce a chimeric antigen receptor, or CAR, into the cell.

The CAR redirects the T-cells to target and destroy pathogenic self-reactive cells.

Our mRNA MSC modality is an allogeneic approach that introduces one or more mRNAs into donor-sourced mesenchymal stem cells, or MSCs, enabling them to produce proteins that target key pathways involved in autoimmunity.

These cells are banked and are designed to be administered off-the-shelf to any patient.

Our mRNA in situ modality is designed to deliver mRNA into a patient’s lymph node to generate CAR-T cells and other proteins that target autoimmunity .

The figure below illustrates each modality.

The table below summarizes key information about our development pipeline.

Our lead product candidate, Descartes-08, is an autologous mRNA CAR-T directed against the B cell maturation antigen, or BCMA, that we are developing for the treatment of autoimmune diseases.

Descartes-08 has been granted Orphan Drug Designation by the FDA for the treatment of MG.

Descartes-08 was observed to be safe and well-tolerated in a Phase 1b/2a trial of 14 patients with MG who received outpatient treatment without pre-treatment chemotherapy.

All seven participants who received six once-weekly infusions at the highest dose continued to experience marked and long-lasting clinical improvement across validated MG disease scoring systems at month nine follow-up.

At month 12, five of these seven participants maintained clinically meaningful improvement.

One participant, who lost response after one year, experienced rapid improvement in clinical scores after re-treatment, which was ongoing at month six of follow-up.

Clinical responses correlated with large reductions in autoantibody titers.

We are currently enrolling in a Phase 2b randomized, double-blind, placebo-controlled trial in patients with MG, for which we expect to report topline results in mid-2024.

Descartes-08 has been granted Orphan Drug Designation and Regenerative Medicine Advanced Therapy, or RMAT, Designation by the FDA for the treatment of MG as well as a Rare Pediatric Disease Designation for the treatment of juvenile dermatomyositis.

Descartes-08 for the Treatment of MG

In July 2024, we reported topline results from a Phase 2b randomized, double-blind, placebo-controlled trial in patients with MG.

The trial achieved its primary endpoint with statistical significance in the pre-specified modified intent-to-treat, or mITT, efficacy population, with 71% (10/14) of patients treated with Descartes-08 observed to have 5-point or greater improvements in MG Composite, or MGC, score at Month 3 compared to 25% (3/12) of patients treated with placebo (p=0.018).

In addition, the trial also achieved its primary endpoint with statistical significance in the per-protocol population, with 69% (11/16) of patients treated with Descartes-08 observed to have 5-point or greater improvements in MGC score at Month 3 compared to 33% (5/15) of patients treated with placebo (p=0.048).

Consistent with previously reported results from the Phase 2a open-label portion of the trial, Descartes-08 responders experienced deep improvements across the MG severity scales at Month 3 (average MG-ADL (Activities of Daily Living) = -5.6;

QMG (Quantitative MG) = -5.0;

QoL-15r (Quality of Life Revised Scale) = -7.9).

A 2-point improvement in MG-ADL and 3-point improvement in MGC and QMG scales are considered “clinically meaningful” by expert consensus published in peer-reviewed journals.

The improvements seen at Month 3 persisted or further improved in patients evaluated at their Month 4 (n=5) and Month 6 (n=3) follow-up visits, as of the June 19, 2024 data cutoff date.

In December 2024, we reported updated results from this trial.

Deepening of responses was observed over time with participants included in the primary efficacy dataset who continued follow-up (n=12) experiencing an average MG-ADL reduction of 5.5 (±1.1) at Month 4.

At Month 4, particularly deep responses were observed in participants without prior exposure to biologic therapies (n=7), including complement or neonatal fragment crystallizable receptor inhibitors, with an average MG-ADL reduction of 6.6 (±1.5).

Responses were observed to further deepen at Month 6, with 33% (4/12) of participants in the primary efficacy dataset and 57% (4/7) of participants with no prior exposure to biologic therapy observed to have minimum symptom expression, defined as an MG-ADL score of 0 or 1.

Responses were observed to be durable through Month 12, with 80% (4/5) of evaluable participants from the primary efficacy dataset maintaining a clinically meaningful response, defined as a reduction in MG-ADL score of at least 2 points.

Of the two participants with no prior exposure to biologic therapy that reached Month 12, both maintained at least a clinically meaningful response, with one continuing to demonstrate minimum symptom expression.

Consistent with previously reported results from the Phase 2a open-label portion of the trial, Descartes-08 continued to be observed as well-tolerated, supporting outpatient administration without the need for lymphodepleting chemotherapy.

Consistent with previously reported data, Descartes-08 was observed to be well-tolerated across the safety dataset (n=36), and adverse events were transient and mostly mild.

Notably, there were no cases of CRS, and no cases of immune effector cell-associated neurotoxicity syndrome, or ICANS.

In addition, treatment with Descartes-08 was not observed to lead to a decrease in vaccine titers for common viruses and was not associated with increased rates of infection or hypogammaglobulinemia.

Within this data readout, we also announced updated trial results from a Phase 2a open-label trial of Descartes-08 in patients with MG from certain retreated patients.

Two participants were previously retreated, and experienced rapid improvement in clinical scores and maintained minimum symptom expression for up to one year after receiving a second

treatment cycle.

A third participant received a second treatment cycle and at the participant’s Month 2 visit, two weeks after the last Descartes-08 infusion, achieved a 4-point reduction in MG-ADL and 6-point reduction in MGC scores from baseline, without reports of CRS or ICANS.

The time course and magnitude of treatment response upon retreatment were similar to the time course and magnitude of treatment response observed when the participants were first treated.

Four of the seven remaining participants from the Phase 2a portion of the trial maintained clinically meaningful responses for at least one year following initial dosing.

We plan to commence our Phase 3 AURORA trial of Descartes-08 in patients with MG in the first half of 2025.

The randomized, double-blind, placebo-controlled Phase 3 AURORA trial is designed to assess Descartes-08 versus placebo (1:1 randomization) administered as six weekly outpatient infusions without preconditioning chemotherapy in approximately 100 participants with acetylcholine receptor autoantibody positive, or AChR Ab+, MG.

The primary endpoint will assess the proportion of Descartes-08 participants with an improvement in MG-ADL score of three points or more at Month 4 compared to placebo.

Secondary endpoints will assess safety and tolerability and the proportion of participants with a reduction of four points or more in MGC score, as well as improvements in other validated MG severity scales, including Quantitative MG, QMG, and MG Quality of Life Revised Scale, or MG-QoL-15R.

In January 2025, we received written agreement from the FDA under the Special Protocol Assessment, or SPA, process on the overall design of our planned AURORA trial.

The SPA agreement indicates that the FDA has determined that the proposed trial design is acceptable to support a future Biologics License Application, or BLA, for Descartes-08 in MG, subject to the ultimate outcome of the trial.

Descartes-08 for the Treatment of Other Autoimmune Diseases

We are also developing Descartes-08 for the treatment of other autoimmune diseases.

We have received FDA allowance for our investigational new drug application, or IND, for a Phase 2 trial of Descartes-08 for the treatment of patients with systemic lupus erythematosus, or SLE, a chronic autoimmune disease that causes systemic inflammation affecting multiple organ systems.

We expect this Phase 2 trial to initiate in the first half of 2024.

In July 2024, the first patient was dosed in our Phase 2 trial of Descartes-08 for the treatment of systemic lupus erythematosus, or SLE, a chronic autoimmune disease that causes systemic inflammation affecting multiple organ systems.

A data readout of this trial is expected in the second half of 2025.

In December 2024, we filed an amendment to the investigational new drug application, or IND, for a pediatric basket trial for juvenile dermatomyositis, or JDM, juvenile SLE, juvenile MG, anti-neutrophil cytoplasmic antibody-associated vasculitis, as well as other conditions.

Our Phase 2 basket trial in pediatric patients is expected to initiate in the second half of 2025.

The FDA has also granted Descartes-08 Rare Pediatric Disease Designation for the treatment of JDM.

The FDA grants Rare Pediatric Disease Designation for serious and life-threatening diseases that primarily affect children ages 18 years or younger and fewer than 200,000 people in the United States.

Under the FDA’s Rare Pediatric Disease Designation and priority review voucher programs, if Decartes-08 is approved for marketing in JDM, Cartesian may qualify for a priority review voucher that can be redeemed to receive priority review of a subsequent marketing application for a different product candidate.

Descartes-15 is our next-generation autologous anti-BCMA mRNA CAR-T.

In preclinical studies, we have observed Descartes-15 to be 10-fold more potent than Descartes-08.

We intend to test the safety of Descartes-15 in an open label, single-arm Phase 1 trial in patients with relapsed/refractory multiple myeloma.

This program has already received IND allowance from the FDA and is expected to enroll the first patient in the first half of 2024.

We expect that these Phase 1 trial data will inform our clinical development plan for Descartes-15 in autoimmune diseases.

Descartes-33 is an allogeneic mRNA MSC in preclinical development for treatment of autoimmune diseases.

We are developing Descartes-33 to deliver a combination of therapeutic proteins that target key drivers in the pathogenesis of autoimmunity.

We are testing the safety of Descartes-15 in an open label, single-arm Phase 1 trial in patients with relapsed/refractory multiple myeloma.

This trial remains ongoing with three patients dosed to date.

We expect that the Phase 1 trial data will inform our clinical development plan for Descartes-15 in autoimmune diseases.

Limitations of Current DNA-Based Cell Therapy Treatments in Autoimmune Disease

Conventional DNA cell therapies have been associated with cytokine release syndrome, neurological toxicities and Parkinsonism, infection, risk of secondary malignancy, and death.

Conventional DNA cell therapies have been associated with CRS, neurological toxicities and Parkinsonism, infection, risk of secondary malignancy, and death.

The acute toxicities are from exponential amplification of the modified cell, and the pre-treatment chemotherapy administered to enable cell amplification.

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Given these risks and requirements, conventional DNA cell therapies are administered under close monitoring in an inpatient setting, increasing their cost and limiting their reach to only the sickest patients.

Limitations of Current Biologic Treatments in Autoimmune Disease

Currently approved biologic therapies for MG, such as complement inhibitors and FcRn inhibitors have significantly improved treatment options, but they come with limitations such as incomplete response, immunosuppression risks, high treatment burden, lack of disease modification and potential for emerging resistance.

Not all patients with AChR+ MG respond adequately to currently approved biologics.

The variability in treatment response may be due to differences in disease mechanisms, with some patients having disease drivers beyond complement activation (for complement inhibitors) or immunoglobulin G, or IgG, reduction (for FcRn inhibitors).

Additionally, some individuals experience an initial improvement but later lose response, requiring adjustments in their treatment strategy.

Biologic therapies used for MG can increase the risk of infections.

Complement inhibitors in particular, heighten susceptibility to Neisseria infections, necessitating vaccination and, in some cases, prophylactic antibiotic use.

Patients receiving FcRn inhibitors may also experience an increased risk of infections due to immunoglobulin depletion.

The long-term safety of these treatments remains an area of active study.

Currently approved biologic therapies require frequent infusions, which can be burdensome for patients.

Efgartigimod requires weekly infusions in repeated cycles, while eculizumab is administered every two weeks and ravulizumab every eight weeks.

While ravulizumab reduces the frequency of infusions compared to eculizumab, both of these treatments require ongoing maintenance, which may impact patient quality of life.

Access to infusion centers or home infusion services further adds to the logistical challenges.

All existing biologic therapies for MG manage symptoms rather than addressing the root cause of the disease.

These treatments do not eliminate the underlying autoimmune process or autoreactive B and T cells, meaning patients typically require lifelong therapy.

While symptom control is critical, the need for continuous treatment highlights the unmet need for therapies that could induce long-term remission.

Finally, the effectiveness of complement inhibitors may vary among patients due to differences in complement system activity or genetic factors.

Some individuals may have upregulated alternative complement pathways or specific gene polymorphisms that reduce the efficacy of eculizumab and ravulizumab.

This variability underscores the importance of identifying biomarkers that could help predict response and guide personalized treatment strategies.

Our Autoimmune Disease Solution

We believe that mRNA cell therapy has the potential to be a potent yet safer alternative to DNA cell therapy for treating autoimmune diseases.

We believe the mRNA cell therapies we are developing have the potential to deliver deep, durable clinical benefit to many patients with autoimmune diseases because they can be administered over a short period of time, in an outpatient setting, and without pre-treatment chemotherapy.

As the data in our clinical trials indicates, the mRNA cell therapies we are developing have the potential to deliver deep and durable clinical benefits to many patients with autoimmune diseases because they can be administered over a short period of time, in an outpatient setting, and without pre-treatment chemotherapy.

These attributes may extend the reach and potential of mRNA cell therapy to a broader group of patients with autoimmunity.

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In other words, a patient’s exposure to our cells is determined by the dose.

The time, course and duration of that exposure are substantially determined by the nature of the mRNA we use.

The time, course and duration of that exposure are substantially determined by

the nature of the mRNA we use.

Therefore, while DNA CAR-T therapies are administered at subtherapeutic levels, we can administer a therapeutic number of mRNA CAR-T cells and re-dose these cells over time, much like a conventional drug.

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Also, because mRNA CAR-T is dosed at a therapeutic dose and does not rely on cell proliferation to reach the therapeutic window, there is no need to administer pre-treatment chemotherapy.

The graphs below contrast our mRNA cell therapy approach with that of conventional DNA cell therapy.

As of the 2023 safety cutoff date, we have administered Descartes-08 to over 60 patients suffering from one of MG, multiple myeloma, and other diseases in open-label trials on an outpatient basis, many at community clinics.

We have not observed product-related cytokine release syndrome, neurotoxicity or infection of any grade.

The most common product-related

adverse events observed—headache, nausea and fever—were self-limited and resolved within 72 hours of onset.

As of December 31, 2024, we have administered Descartes-08 to over 100 patients suffering from one of MG, multiple myeloma, and other diseases in open-label trials on an outpatient basis, many at community clinics.

We have not observed product-related CRS, neurotoxicity or infection of any grade.

The most common product-related adverse events observed, headache, nausea, and fever, were self-limited and resolved within 72 hours of onset.

One participant with MG with a history of allergic reaction to biologics developed hives after the third infusion and was hospitalized for monitoring.

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Our Product Candidates

Our lead product candidate is Descartes-08, a potential first-in-class mRNA CAR-T.

Descartes-08 targets BCMA, which exists on the surface of long-lived plasma cells, or LLPCs, and plasmacytoid dendritic cells, or pDCs.

LLPCs, which can survive for decades, are the main producers of disease-causing autoantibodies.

pDCs, which secrete type-I interferons, may also play a critical role in autoimmunity.

While the lead indication for Descartes-08 is MG, we believe that Descartes-08 has potential to treat other autoimmune diseases, such as lupus.

Descartes-08, our lead mRNA cell therapy candidate, is an autologous mRNA CAR-T product targeting BCMA in clinical development for generalized MG and SLE.

In contrast to conventional DNA-based CAR T-cell therapies, mRNA CAR-T administration is designed to not require preconditioning chemotherapy, can be administered in the outpatient setting, and does not carry the risk of genomic integration associated with cancerous transformation.

Descartes-08 has been granted Orphan Drug Designation and RMAT Designation by the FDA for the treatment of MG, and Rare Pediatric Disease Designation for the treatment of JDM.

Descartes-08 for the Treatment of MG

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This results in muscle weakness in tissues throughout the body, potentially manifesting in partial paralysis of eye movements, problems in chewing and swallowing, respiratory problems, speech difficulties and weakness in skeletal muscles.

The symptoms of the disease can be transient and in the early stages of the disease can remit spontaneously.

However, as the disease progresses, symptom-free periods become less frequent and disease exacerbations can last for months.

As the disease progresses, symptom-free periods become less frequent and disease exacerbations can last for months.

Disease symptoms reach their maximum levels within two to three years in approximately 80% of patients.

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Clinical Development

To date, we have completed the Phase 1b portion of the Phase 1/2 trial of Descartes-08 in MG, as well as the primary readout of the Phase 2a portion of the trial.

We continue to enroll patients to the Phase 2b portion of the trial.

To date, we have completed the Phase 1/2 trial of Descartes-08 in MG, which consisted of a Phase 1b portion, a Phase 2a portion, and a Phase 2b portion.

The primary objective of the Phase 1b portion of the trial was to determine the maximum tolerated dose of Descartes-08 for patients with MG.

To assess the safety and manufacturability of Descartes-08, the product candidate was administered in three ascending doses (3.5 x10 6 cells/kg;

17.5 x10 6 cells;

52.5 x10 6 cells/kg) to three patients with MG.

After each infusion, patients were observed for at least one week, and a higher dose level was administered if there were no significant adverse effects observed at the initial dose.

We observed Descartes-08 to be well-tolerated by the three patients who participated in this portion of the trial with no cytokine release syndrome or other serious product-related adverse events.

We observed Descartes-08 to be well-tolerated by the three patients who participated in this portion of the trial with no CRS or other serious product-related adverse events.

The primary objective of the Phase 2a portion of the trial was to determine the optimal dosing schedule for patients with MG using the highest dose level tested in Phase 1b (52.5 x106 cells/kg).

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This portion of the trial evaluated 11 patients with particularly advanced disease as assessed by both patient and clinician-reported outcomes.

79% of the 14 patients included in the Phase 1b and Phase 2a portions of the trial were classified at screening to have Class III or IV disease, as defined by the Myasthenia Gravis Foundation of America, indicating they have moderate-to-severe weakness affecting their muscles.

79% of the 14 patients included in the Phase 1b and Phase 2a portions of the trial were classified at screening to have Class III or IV disease, as defined by the Myasthenia Gravis Foundation of America, indicating they had moderate-to-severe weakness affecting their muscles.

The results of the Phase 2a portion of the trial, published in the Lancet Neurology in July 2023, indicated that after six weekly infusions of Descartes-08, the average improvement in all disease severity scores was three-to-five-fold greater than what is considered clinically meaningful by expert consensus.

As shown in the figure below, clinical improvements persisted in all patients at month nine, and in five of the seven remaining patients at a final, 12-month follow-up.

Of the two participants who lost response, one was retreated and experienced rapid improvement in clinical scores, which was ongoing at month six of

Descartes-08 was observed to be well-tolerated with no reports of dose-limiting toxicities, cytokine release syndrome or neurotoxicity.

As shown in the figure below, clinical improvements persisted in all patients at Month 9, and in five of the seven remaining patients at a final, 12-month follow-up.

Descartes-08 was observed to be well-tolerated with no reports of dose-limiting toxicities, CRS or neurotoxicity.

Mean change from Baseline (line) and standard error (bands) in Myasthenia Gravis Activities of Daily Living Score (MG-ADL, A), Quantitative Myasthenia Gravis Score (QMG, B), Myasthenia Gravis Composite Score (MGC, C) during 12 months of follow-up for MG-001 participants who received six once-weekly doses (n=7).

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MGC and QMG are neurologist-assessed.

Change from Baseline in MGC Score after initial dosing and retreatment in a participant experiencing relapse at Month 12.

Relative change in serum anti-acetylcholine receptor antibody levels in the three participants with detectable antibodies at baseline.

Each line represents one patient.

All three participants with detectable anti-acetylcholine receptor antibody levels before treatment had an average 42% reduction in antibody levels by month six.

These reductions deepened to 68% by month nine and persisted at month 12.

All three participants with detectable anti-acetylcholine receptor antibody levels before treatment had an average 42% reduction in antibody levels by Month 6.

These reductions deepened to 68% by Month 9 and persisted at Month 12.

In summary, we observed continued clinical improvement and autoantibody reductions after BCMA directed mRNA CAR-T treatment for MG that persisted through the one-year follow-up period.

We are currently enrolling patients in the Phase 2b randomized, double-blind, placebo-controlled portion of the Phase 1/2 trial.

We expect to report topline results in mid-2024.

The trial, which is expected to have at least 30 completers, is designed to assess the primary endpoint of the proportion of patients achieving a five-point or greater reduction in their MGC score at day 85.

Patients will receive six weekly infusions at the dose established in Phase 1b (52.5 x10 6 cells/kg).

The trial also involves a crossover component, in which any patient originally assigned to placebo will be given the opportunity to receive Descartes-08 after completing trial treatment.

Secondary endpoints are designed to assess a variety of additional clinical outcomes, including determining safety and tolerability, quantifying the clinical effect of Descartes-08 over one year, assessing changes through day 85 in QMG, MG QoL 15R, MG Composite and MG post-intervention status and comparing the effect of Descartes-08 versus placebo on MG scales through day 85 in patients who cross over from placebo to Descartes-08.

Follow-on results of the Phase 2b portion of the trial were presented in December 2024.

The trial reached its primary endpoint to assess the proportion of patients achieving a five-point or greater reduction in their MGC score at day 85.

Patients received six weekly infusions at the dose established in Phase 1b (52.5 x106 cells/kg).

The trial also involved a crossover component, in which any patient originally assigned to placebo was given the opportunity to receive Descartes-08 after completing trial treatment.

In the Phase 2b trial, we observed a deepening of responses after Month 3 in the primary efficacy data set.

Two MG composite responders at Month 3 withdrew from the study before Month 4 for personal reasons (total number of participants at Month 4 and Month 6 was 12).

Of the 12 participants as of the readout date, eight had reached Month 9 follow-up and five had reached Month 12 follow-up, thus completing the trial.

Results of the study showed an average MG-ADL reduction of 5.5 points at Month 4 (chart below on the left) and an average MGC reduction of 7.1 for Descartes-08 treated patients (chart below on the right), both of which exceed the thresholds clinicians generally consider clinically meaningful, defined as a reduction in MG-ADL score of at least two points and a reduction in MGC score of at least three points.

Additionally, at Month 6, one third of all participants were observed to achieve minimal symptom expression.

This is consistent with what we observed in the Phase 2a trial, where deepest responses were observed to occur at Month 6 and Month 9.

Additionally, 80% of all participants who reached Month 12, including both responders and non-responders at Month 3, were observed to maintain clinically meaningful responses as measured by both MG-ADL and MGC.

We also observed that 57% of the participants with no prior exposure to biologic therapy, achieved minimal symptom expression at Month 6.

Of the two participants with no prior exposure to biologic therapy that reached Month 12, both were observed to maintain at least a clinically meaningful response with one continuing to maintain minimal symptom expression.

The safety profile observed in the follow-up portion of the Phase 2b trial was in line with what we reported at the time of our top line data readout as well as the Phase 2a portion of the trial.

Of note, there was a Grade 2 upper respiratory infection reported in both the Descartes-08 and placebo groups.

There were no other new adverse events, or AEs, reported, including no hypogammaglobulinemia and other infections and no difference in vaccine titers between Descartes-08 and placebo.

We previously reported that there were three participants in the Phase 2a portion of the trial who were observed to have a response to Descartes-08, but then reverted to baseline, two patients one year after treatment and the other 1.5 years after treatment.

As previously reported, there were two participants who were retreated and experienced rapid improvements in clinical scores and maintained minimum symptom expression for up to one year after receiving a second treatment cycle.

The time course and magnitude of treatment response upon retreatment were similar to those seen when the participants were first treated.

Notably, in the one participant who completed their 12-month retreatment follow-up visit, the duration of response was observed to be longer than that patient’s initial response, and this patient had maintained minimum symptom expression at Month 12.

The third retreated participant, at their Month 2 visit, which was 2 weeks after their last Descartes-08 infusion, achieved a 4-point reduction in MG-ADL and 6-point reduction in MGC scores from baseline, without reports of CRS or ICANS.

Descartes-08 for the Treatment of Systemic Lupus Erythematosus

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The most common manifestations of SLE are cutaneous and musculoskeletal symptoms, although neurological, gastrointestinal, hematological, and renal symptoms are regularly observed as well.

Patients with SLE are at a substantially increased risk of

infection and cardiovascular disease, contributing to estimated 10- and 15-year mortality rates of 9% and 15%, respectively.

Patients with SLE are at a substantially increased risk of infection and cardiovascular disease, contributing to estimated 10- and 15-year mortality rates of 9% and 15%, respectively.

SLE is the most common form of lupus, representing approximately 70% of lupus patients, and approximately three million adults worldwide are estimated to have SLE.

We expect to initiate a multi-center open-label single-arm Phase 2 trial, for which we have received FDA IND allowance, in the first half of 2024.

We recently initiated a multi-center open-label single-arm Phase 2 trial, for which we have received FDA IND allowance.

The primary objective of this trial is to evaluate the safety, tolerability, and manufacturing feasibility of Descartes-08 mRNA CAR-T cells administered as six once-weekly outpatient infusions of 52.5x106 cells/kg without pre-treatment chemotherapy in approximately 30 patients with SLE.

We also filed an amendment to the IND application with our Descartes-08 product candidate in pediatric autoimmune disease in December 2024.

This Phase 2 SLE trial of Descartes-08 remains ongoing and a preliminary data readout is expected in the second half of 2025.

Descartes-15 is a next-generation, autologous anti-BCMA mRNA CAR-T.

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We observed that Descartes-15 was 10-fold more potent than Descartes-08 in preclinical studies, as illustrated in the below charts.

In November 2023, we received IND allowance from the FDA to initiate the Phase 1 trial to test the safety of Descartes-15 in patients with multiple myeloma.

We intend to leverage our preclinical and clinical observations from the Descartes-08 development program and the Descartes-15 Phase 1 program to inform our clinical strategy for Descartes-15 for the treatment of autoimmune diseases.

Allogeneic Product Candidate

Descartes-33 is our allogeneic mRNA MSC in preclinical development for treatment of autoimmune diseases.

We are developing Descartes-33 to deliver a combination of therapeutic proteins that target key drivers in the pathogenesis of autoimmunity.

In November 2023, we received IND allowance from the FDA to initiate the Phase 1 trial to test the safety of Descartes-15 in patients with multiple myeloma and dosing is underway in this trial.

The Phase 1 dose escalation trial is designed to assess the safety and tolerability of outpatient Descartes-15 administration in patients with multiple myeloma.

Following the Phase 1 dose escalation trial, we expect to subsequently assess Descartes-15 in autoimmune indications.

Manufacturing

We have established wholly-owned internal manufacturing and research and development capabilities, which allow us to optimize processes rapidly and in an iterative manner.

Our main manufacturing facility is located in Gaithersburg, Maryland and operates under current good manufacturing practice, or cGMP.

This facility enhances our control of product quality and production schedules and costs, allowing us to move assets from discovery to preclinical to clinical development quickly.

We also entered into an agreement to lease additional manufacturing space located in Frederick, Maryland to transition and expand our clinical and commercial manufacturing capabilities for our maturing pipeline of innovative mRNA cell therapies for the treatment of autoimmune disease.

Our cGMP cell manufacturing facilities, with their dedicated quality management system, are also capable of mRNA production used in Descartes-08.

Our main manufacturing facility is located in Frederick, Maryland, and operates under current good manufacturing practice, or cGMP.

This facility has sufficient capacity to support current clinical needs and can potentially transition to support commercial manufacturing of our maturing pipeline of innovative mRNA cell therapies for the treatment of autoimmune diseases.

We believe the Frederick facility will allow us to scale our wholly-owned, in-house cGMP manufacturing capabilities for late-stage clinical and commercial supply of our mRNA cell therapy product candidates, while continuing to maintain control over product quality and production.

We also maintain additional manufacturing space located in Gaithersburg, Maryland.

We manufacture Descartes-08 in-house and are typically able to process and release lots for infusion within approximately three weeks.

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We have optimized our manufacturing processes through over 200 cGMP runs.

We also maintain FDA-reviewed human umbilical cord MSC cell collection and banking operations.

Intellectual Property

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Our success also depends in part on our ability to operate without infringing, misappropriating or otherwise violating the proprietary rights of others, and in part on our ability to prevent others from infringing, misappropriating or violating our proprietary rights.

A discussion of risks relating to intellectual property is provided under the section titled “ Risk factors—Risks related to intellectual property.”

A discussion of risks relating to intellectual property is provided under the section titled “Risk Factors—Risks Related to Our Intellectual Property.”

We intend to continue developing intellectual property, and we intend to aggressively protect our position in key technologies.

Our patents are focused on several key technologies, including the use of our mRNA CAR-T technology and other developments in our mRNA cell therapy pipeline.

As of December 31, 2023, we had five issued patents worldwide, including two patents issued in the United States and three issued outside the United States.

Our patents are set to expire on various dates in 2040 through 2043.

Additionally, as of December 31, 2023, we had 14 patent applications pending worldwide, including five U.S.

applications and nine applications outside the United States.

As of December 31, 2024, we had seven issued patents worldwide, including three patents issued in the United States (U.S.

10,934,337, 11,220,535, and 11,999,773) and four patents issued outside the United States (Japanese Patent No.

7,379,654, Canadian Patent No.

3,158,025, Israeli Patent No.

285909, and Korean Patent No.

Our issued patents and any patents issuing from our pending applications are set to expire on various dates in 2040 through 2044.

Additionally, as of December 31, 2024, we had 13 patent applications pending worldwide, including three U.S.

applications, eight applications in ex-U.S.

jurisdictions, and 2 International (PCT) applications.

A patent granted on U.S.

Patent Application No.

18/654,279 will expire on March 13, 2040, a patent granted on U.S.

Patent Application No.

17/919,092 will expire on April 15, 2041, and a patent granted on U.S.

Patent Application No.

18/292,670 will expire on July 28, 2042, barring any potential patent term adjustment or terminal disclaimers.

patent applications are directed to compositions of matter, and U.S.

Patent Application No.

18/292,670 is also directed to methods of use.

In addition, PCT/US2024/020251 was filed on March 15, 2024, a composition-of-matter and method-of-use PCT application, and any national stage application based on it will expire on March 15, 2044.

Also, PCT/US2024/020815 was filed on March 20, 2024, a composition-of-matter and method-of-use PCT application, and any national stage applications based on it will expire on March 20, 2044.

In addition, a patent granted on any of European patent application 20773688.5, AU 2020241428, CA 3199205, CN 202080020956.1, IN 202117036675, KR 2023-7034215, or MX/a/2021/011196 will expire March 2040 and a patent granted on European patent application 21789568.9 will expire April 2041.

All of these patent applications are composition-of-matter applications.

In addition, we had two registered marks protecting our brand and prospective products both domestically and internationally.

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However, such confidentiality agreements can be breached, and we may not have adequate remedies for any such breach.

For more information regarding the risks related to our intellectual property, see the section titled “ Risk factors—Risks related to intellectual property .”

For more information regarding the risks related to our intellectual property, see the section titled “Risk factors—Risks Related to Our Intellectual Property.”

Key Agreements

Biogen License Agreement

On September 8, 2023, we entered into a non-exclusive, sublicensable, worldwide, perpetual patent license agreement, or the Biogen Agreement, with Biogen MA, Inc, or Biogen, to research, develop, make, use, offer, sell and import products or processes containing or using an engineering T-cell modified with an mRNA comprising, or encoding a protein comprising, certain sequences licensed under the Biogen Agreement for the prevention, treatment, palliation and management of autoimmune diseases and disorders, excluding cancers, neoplastic disorders, and paraneoplastic disorders.

On September 8, 2023, we entered into a non-exclusive, sublicensable, worldwide, perpetual license agreement, or the Biogen Agreement, with Biogen MA, Inc., or Biogen, to research, develop, make, use, offer, sell and import products or processes containing or using an engineering T-cell modified with an mRNA comprising, or encoding a protein comprising, certain sequences licensed under the Biogen Agreement for the prevention, treatment, palliation and management of autoimmune diseases and disorders, excluding cancers, neoplastic disorders, and paraneoplastic disorders.

We are not obligated to pay Biogen any expenses, fees, or royalties.

We may terminate the Biogen Agreement for any reason or no reason, and Biogen may terminate the agreement after a notice-and-cure period of 30 days if we fail to pay a fee owed to Biogen or for any other material breach of the agreement.

The Biogen Agreement will otherwise expire when all claims of all issued patents within the patents and patent applications licensed

to us under the Biogen Agreement have expired or been finally rendered revoked, invalid or unenforceable by a decision of a court or government agency.

The Biogen Agreement will otherwise expire when all claims of all issued patents within the patents and patent applications licensed to us under the Biogen Agreement have expired or been finally rendered revoked, invalid or unenforceable by a decision of a court or government agency.

The Biogen Agreement encompasses patents and patent applications in the PCT/US2010/026825 patent family, which was filed March 10, 2010.

In general, all patents that issue in this family have an expected expiration date of March 10, 2030, subject to potential patent term adjustments and/or extensions.

patents and applications in this family, U.S.

Patent 9,034,324 was awarded 677 days of patent term adjustment, which would extend the expiration date of this patent to January 16, 2032, absent any challenges to the patent term.

The other issued patent in this family was not awarded any patent term adjustment, so its expected expiration date is March 10, 2030.

NCI License Agreement

Effective September 16, 2019, we entered into a nonexclusive, worldwide license agreement, or the NCI Agreement, with the U.S.

Effective September 16, 2019, we entered into a non-exclusive, worldwide license agreement, or the NCI Agreement, with the U.S.

Department of Health and Human Services, represented by the National Cancer Institute of the National Institutes of Health, or NCI.

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Prior to the first commercial sale, upon NCI’s request, we are obligated to provide NCI with commercially reasonable quantities of licensed products made through licensed processes to be used for in vitro research.

Additionally, we must use reasonable commercial efforts to initiate a Phase 3 clinical trial of a licensed product by the fourth quarter of 2024, submit a biologics license application, or BLA, with respect to a licensed product by the fourth quarter of 2026, and make a first commercial sale of a licensed product by the fourth quarter of 2028.

Additionally, we must use reasonable commercial efforts to initiate a Phase 3 clinical trial of a licensed product by the fourth quarter of 2024, submit a BLA with respect to a licensed product by the fourth quarter of 2026, and make a first commercial sale of a licensed product by the fourth quarter of 2028.

The NCI Agreement terminates upon the expiration of the last to expire of the patent rights licensed thereunder, if not sooner terminated.

NCI has the right to terminate this agreement, after giving written notice and providing a cure period in accordance with its terms, if we are in default of a material obligation.

The NCI License Agreement encompasses patents and patent applications in the PCT/US2013/032029 patent family, which was filed March 15, 2013.

In general, all patents that issue in this family have an expected expiration of March 15, 2033, subject to potential patent term adjustments and/or extensions.

patents and applications in this family, only two patents were awarded patent term adjustments.

Patent 9,765,342 was awarded 297 days of patent term adjustment, which would extend the expiration date of this patent to January 6, 2034, absent any challenges to the patent term.

The other patent, U.S.

Patent 10,876,123, was awarded three days of patent term adjustment, but this patent is subject to terminal disclaimers filed against other family members, so this patent will not extend beyond the March 15, 2033 date.

The other issued patents in this family were not awarded any patent term adjustment, so the expected expiration date for these patents also remains March 15, 2033.

There is also a pending patent application which, if issued, will expire on March 15, 2033, but could also be subject to patent term adjustment and to any potential future terminal disclaimers.

NCI has the right to

terminate this agreement, after giving written notice and providing a cure period in accordance with its terms, if we are in default of a material obligation.

We have the unilateral right to terminate the agreement in any country or territory by giving NCI 60 days’ written notice.

We agreed to indemnify NCI against any liability arising out of our, sublicensees’ or third-parties’ use of the licensed patent rights and licensed products or licensed processes developed in connection with the licensed patent rights.

Astellas License Agreement

On January 8, 2023, we entered into a License and Development Agreement, or the Astellas Agreement, with Audentes Therapeutics, Inc., or Astellas.

Under the Astellas Agreement, we granted Astellas an exclusive license to the Company’s IdeXork technology arising from Xork, to develop and commercialize Xork for use in Pompe disease in combination with an Astellas gene therapy investigational or authorized product.

Xork, a bacterial IgG protease licensed from Genovis AB (publ.), or Genovis, is licensed pursuant to an Exclusive License Agreement with Genovis, or the Genovis Agreement.

Astellas paid to us a $10.0 million upfront payment upon signing of the Astellas Agreement, and we are entitled to receive up to $340.0 million in future additional payments over the course of the partnership that are contingent on the achievement of various development and regulatory milestones and, if commercialized, sales thresholds for annual net sales where Xork is used as a pre-treatment for an Astellas investigational or authorized product.

We are also eligible for tiered royalty payments ranging from low to high single digits.

Any proceeds received from milestone payments or royalties relating to Xork would be required to be distributed to holders of CVRs, net of certain deductions.

Pursuant to the Astellas Agreement, we will have the exclusive right and responsibility to complete research and development of Xork products and to conduct all preclinical studies and clinical trials for Xork for use in Pompe disease with an Astellas gene therapy investigational or authorized product, or the Xork Development Services.

Astellas will reimburse us for 25% of all budgeted costs incurred to complete the development of Xork for use in Pompe disease with an Astellas gene therapy investigational or authorized product.

We will have control and responsibility over regulatory filings, including any IND, BLA, and marketing authorization applications relating to the licensed product.

Astellas will have the exclusive right and responsibility to research, develop, and commercialize Astellas products used in combination with Xork and will have control and responsibility over all regulatory filings, including any IND, BLA, and marketing authorization applications, relating to Astellas products and Astellas products used in combination with Xork.

Sobi License Agreement

On June 11, 2020, we entered into a License and Development Agreement with Swedish Orphan Biovitrum AB (publ.), or Sobi, which was amended on October 31, 2023, or, as so amended, the Sobi License.

Pursuant to the Sobi License, we agreed to grant Sobi an exclusive, worldwide (except as to Greater China) license to develop, manufacture and commercialize the SEL-212 drug candidate, which is currently in development for the treatment of chronic refractory gout.

The SEL-212 drug candidate is a pharmaceutical composition containing a combination of SEL-037, or the Compound, and ImmTOR.

Pursuant to the Sobi License, in consideration of the license, Sobi agreed to pay us a one-time, upfront payment of $75.0 million.

Sobi has also agreed to make milestone payments totaling up to $630.0 million to us upon the achievement of various development and regulatory milestones and, if commercialized, sales thresholds for annual net sales of SEL-212, and tiered royalty payments ranging from the low double digits on the lowest sales tier to the high teens on the highest sales tier.

Pursuant to the Sobi License, we granted Sobi an exclusive, worldwide (except as to Greater China) license to develop, manufacture and commercialize a drug candidate known as SEL-212, which is currently in development for the treatment of chronic refractory gout.

Pursuant to the Sobi License, Sobi agreed to make milestone payments totaling up to $630.0 million to us upon the achievement of various development and regulatory milestones and, if commercialized, sales thresholds for annual net sales of SEL-212, and tiered royalty payments ranging from the low double digits on the lowest sales tier to the high teens on the highest sales tier.

Any proceeds received from milestone payments or royalties relating to the Sobi License would be required to be distributed to holders of CVRs, net of certain deductions.

Pursuant to the Sobi License, we agreed to supply (at cost) quantities of the Compound and ImmTOR as necessary for completion of the two Phase 3 clinical trials of SEL-212 (DISSOLVE I and DISSOLVE II) and a six-month placebo extension.

We were required to supply quantities of the Compound until all rights to the Compound and any materials needed to manufacture the Compound were transferred to Sobi, which transfer occurred upon the execution of Amendment No.

1 to the License and Development Agreement on October 31, 2023.

Sobi agreed to reimburse us for all budgeted costs incurred to complete development of SEL-212, including but not limited to costs incurred while conducting and completing the Phase 3 DISSOLVE trials, except for any costs of additional development activities required that are related to ImmTOR and that are unrelated to SEL-212.

Sobi will have control and responsibility over all regulatory filings, including any IND, BLA, and marketing authorization applications relating to the licensed product.

The transactions contemplated by the Sobi License were consummated on July 28, 2020.

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Government authorities in the United States, at the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing, manufacturing, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing.

We believe our cell therapy product candidates are subject to regulation in the United States as “biologics” or “biological products”.

We expect to seek approval of Descartes-08 through a single BLA reviewed by FDA’s Center for Biologics Evaluation and Research, or CBER.

Biological products are subject to regulation under the Federal Food, Drug, and Cosmetic Act, or FD&C Act and the Public Health Service Act, or PHS Act, and other federal, state, local and foreign statutes and regulations.

We believe our cell therapy product candidates are subject to regulation in the United States as “biologics” or “biological products.” We expect to seek approval of Descartes-08 through a single BLA reviewed by FDA’s Center for Biologics Evaluation and Research, or CBER.

Biological products are subject to regulation under the Federal Food, Drug, and Cosmetic Act, or the FD&C Act, and the Public Health Service Act, or the PHS Act, and other federal, state, local and foreign statutes and regulations.

Descartes-08 and any other product candidates that we develop must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in foreign countries.

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Clinical trials must be conducted and monitored in accordance with the FDA’s regulations, including with respect to good clinical practice, or GCP, requirements, including the requirement that all research subjects provide informed consent.

Further, each clinical study must be reviewed and approved by an independent institutional review board, or IRB, at or servicing each institution at which the clinical study will be conducted.

Further, each clinical study must be reviewed and approved by an institutional review board, or IRB, at or servicing each institution at which the clinical study will be conducted.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

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Cell and gene therapy products may differ from the traditional clinical trial phases.

For example, clinical trials for cell and gene therapy products are often structured as a hybrid Phase 1/2 study where a small group of participants with the disease are enrolled and both safety and efficacy tests are performed.

For example, clinical trials for cell and gene therapy products are often structured as a hybrid Phase 1/2 trial where a small group of participants with the disease are enrolled and both safety and efficacy tests are performed.

Through the SPA process, a sponsor may seek agreement from the FDA on critical features of a proposed protocol for their adequacy to support marketing approval.

In response to a request for an SPA agreement, the FDA issues a letter to the sponsor indicating its agreement or non-agreement with elements of the proposed protocol.

An SPA agreement documents the FDA’s concurrence with the adequacy and acceptability of specific critical elements of the protocol design, and the FDA may not change an SPA agreement once the trial is underway unless the sponsor or applicant agrees in writing or the FDA identifies a

substantial scientific issue essential to determining the safety or effectiveness of the drug after the testing has begun.

Even if the sponsor conducts the trial in accordance with an SPA agreement and the trial meets its endpoints with statistical significance, there is no guarantee that the FDA will accept or approve a marketing application.

For example, the FDA could determine that the overall balance of risks and benefits for the product candidate is not adequate to support approval, or only justifies approval for a narrow set of clinical uses or approval with restricted distribution or other post-approval requirements or limitations.

Post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up.

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The FDA may waive the review by an advisory committee and is not bound by the recommendation of an advisory committee, but it often follows such recommendations.

During the biological product approval process, the FDA also will review proposed product labeling and will determine whether a Risk Evaluation and Mitigation Strategy, or REMS, is necessary to assure the safe use of the biological product candidate.

During the biological product approval process, the FDA also will review proposed product labeling and will determine whether a Risk Evaluation and Mitigate Strategy, or REMS, is necessary to assure the safe use of the biological product candidate.

If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS;

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Before approving a BLA, the FDA will inspect the facilities in which the product is manufactured to determine whether the manufacturing processes and facilities are in compliance with cGMPs.

The FDA may also audit the clinical investigation sites to determine that they have complied with good clinical practices.

The FDA may also audit the clinical investigation sites to determine that they have complied with GCPs.

Notwithstanding the submission of relevant data and information, the FDA may ultimately deny approval or seek additional information from the applicant.

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One of the performance goals agreed to by the FDA under PDUFA is to review 90% of standard BLAs in 10 months from the filing date and 90% of priority BLAs in six months from the filing date, whereupon a review decision is to be made.

Two additional months are added to these timelines for new molecular entities.

additional months are added to these timelines for new molecular entities.

The FDA does not always meet its PDUFA goal dates for standard and priority BLAs.

Orphan Designation

individuals in the United States, there is no reasonable expectation that the cost of developing and marketing the product for this type of disease or condition will be recovered from sales in the United States.

Prior to the submission of a BLA, the FDA may grant orphan designation to drugs or biologics intended to treat a rare disease or condition that affects fewer than 200,000 individuals in the United States, or if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and marketing the product for this type of disease or condition will be recovered from sales in the United States.

After the FDA grants orphan designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

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Fast Track, priority review, accelerated approval, and breakthrough therapy designations do not change the standards for approval and may not necessarily expedite the development or approval process.

In 2016, the 21 st Century Cures Act established what the FDA describes as a regenerative medicine adventure therapy, or RMAT, designation.

In 2016, the 21st Century Cures Act established what the FDA describes as RMAT designation.

The RMAT designation program is intended to facilitate an efficient development program for, and expedite review of, any product that meets the following criteria:

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(ii) the product is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition;

and (iii) preliminary clinical evidence indicates that the product has the potential to address

unmet medical needs for such a disease or condition.

and (iii) preliminary clinical evidence indicates that the product has the potential to address unmet medical needs for such a disease or condition.

RMAT designation provides all the benefits of Breakthrough Therapy Designation, including early interactions to discuss any potential surrogate or intermediate endpoints to be used to support accelerated approval, eligibility for rolling review and potential eligibility for priority review.

Product candidates granted RMAT designation may also be eligible for accelerated approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of clinical trial sites, including through expansion of trials to additional sites, as appropriate.

Descartes-08 has been granted RMAT designation for the treatment of MG.

Post-approval Requirements

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The FDA has approved a number of products under these provisions.

To the Company’s knowledge, the definition of “biosimilar” with regard to an mRNA-modified cell therapy has not been expressly stated in statute, regulation, or guidance, and has not been reviewed by a court.

To our knowledge, the definition of “biosimilar” with regard to an mRNA-modified cell therapy has not been expressly stated in statute, regulation, or guidance, and has not been reviewed by a court.

The regulatory pathway for a biosimilar to one of our products thus remains somewhat uncertain.

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In the European Economic Area, or EEA, which is composed of the 27 member states of the European Union, or EU, plus Norway, Iceland and Liechtenstein, medicinal products can only be commercialized after obtaining a Marketing Authorization, or MA.

To obtain an MA in the EEA, we must submit a marketing authorization application, which is similar to the U.S.

There are two types of MAs.

The EU MA, which is issued by the European Commission through the Centralized Procedure, based on the opinion of the Committee for Medicinal Products for Human Use, or CHMP, of the European Medicines Agency, or EMA, and which is valid throughout the entire territory of the EEA.

The EU MA, which is issued by the European Commission through the Centralized Procedure, is based on the opinion of the Committee for Medicinal Products for Human Use, or CHMP, of the European Medicines Agency, or EMA, and is valid throughout the entire territory of the EEA.

The Centralized Procedure is mandatory for certain types of products, such as biotechnology medicinal products, orphan medicinal products, advanced therapy medicinal products (comprising gene therapy, somatic cell therapy and tissue engineered products), among others.

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If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in various Member States through the Decentralized Procedure.

To obtain regulatory approval of medical product under EU regulatory systems, we must submit a marketing authorization application, which is similar to the U.S.

The EU also provides opportunities for market exclusivity.

Upon receiving marketing authorization, “new active substances” generally receive eight years of data exclusivity, which prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar application, and an additional two years of market exclusivity, during which no generic or biosimilar product can be marketed.

However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new active substance, and products may not qualify for data exclusivity.

Products receiving orphan designation in the EU can receive ten years of market exclusivity, during which time no marketing authorization application shall be accepted, and no marketing authorization shall be granted for a similar medicinal product for the same indication.

An orphan product can also obtain an additional two years of market exclusivity in the EU for pediatric studies.

No extension to any supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications.

EU law also provides opportunities for market exclusivity.

Upon receiving MA, “new active substances” generally receive eight years of data exclusivity, which prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic or biosimilar application, and an additional two years of market exclusivity, during which no generic or biosimilar product can be marketed.

The ten years of exclusivity will 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.

However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new active substance which would be eligible for the relevant periods of data and market exclusivity.

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

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Orphan medicinal products are eligible for certain financial and exclusivity incentives.

In particular, orphan medicinal products in the EU can receive ten years of market exclusivity, during which time no MA application shall be accepted, and no MA shall be granted for a similar medicinal product for the same indication.

The 10-year market exclusivity for orphan medicinal products 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.

Additionally, MA may be granted to a similar product during the 10-year period of market exclusivity for the same therapeutic indication at any time in certain circumstances, including if the second applicant can establish in its application that its product, although similar to the orphan medicinal product already authorized, is safer, more effective or otherwise clinically superior.

In the EU, for any new medicinal product that is protected by or eligible for a supplementary protection certificate, pediatric clinical trials must be conducted in accordance with a pediatric investigation plan, or PIP, that has been approved by the EMA.

Normally, the pediatric clinical trials must be completed before the initial MA application for the relevant indication.

However, the EMA may grant a deferral of the studies in order not to delay the approval of the product in adults and the EMA may waive the requirement to conduct studies in certain circumstances, such as if the relevant condition does not occur in

If pediatric clinical trials are completed in accordance with an agreed PIP, the product will be entitled to a six-month extension of its supplementary protection certificate.

However, if the product is authorized as an orphan medicinal product, it is entitled to a two-year extension of its 10 years of orphan exclusivity and not to an extension of the supplementary protection certificate.

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

In all cases, again, the clinical studies are conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

When conducting clinical trials in the EU, we must adhere to the provisions of the EU Clinical Trials Directive (Directive 2001/20/EC) and the laws and regulations of the EU Member States implementing them.

These provisions require, among other things, that the prior authorization of an Ethics Committee and the competent Member State authority is obtained before commencing the clinical trial.

In 2014, the EU passed the Clinical Trials Regulation (Regulation 536/2014), which will replace the current Clinical Trials Directive, to ensure that the rules for clinical trials are identical throughout the EU.

When conducting clinical trials in the EU, we must adhere to the provisions of the EU Clinical Trials Regulation (EU) No 536/2014.

If the sponsor of the clinical trial is not established within the EU, it must appoint an entity within the EU to act as its legal representative, who shall be responsible for ensuring compliance with the sponsor’s obligations under the Regulation and be the addressee for all communications.

The sponsor must take out a clinical trial insurance policy, and in most EU countries the sponsor is liable to provide ‘no fault’ compensation to any study subject injured in the clinical trial.

Prior to commencing a clinical trial in the EU, we must obtain a clinical trial authorization, or CTA, in each Member State in which the trial will be conducted.

There is a centralized application procedure where one national authority leads the scientific review of the application, while each concerned member state complete an ethical review of any CTA.

The application for a CTA must include, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation.

Any substantial changes to the trial protocol or other information submitted with the CTAs must be notified to or approved by the relevant competent authorities.

We are also subject to data privacy and security laws in the jurisdictions outside of the U.S.

in which we are established, run clinical trials or in which we sell or market our products once approved.

For example, in Europe we are subject to Regulation (EU) 2016/679 (General Data Protection Regulation, or GDPR) in relation to our collection, control, processing and other use of personal data (i.e., data relating to an identifiable living individual).

For example, in Europe we are subject to Regulation (EU) 2016/679 (General Data Protection Regular, or GDPR) in relation to our collection, control, processing and other use of personal data (i.e., data relating to an identifiable living individual).

We process personal data in relation to participants in our clinical trials in the EEA, including the health and medical information of these participants.

The GDPR is directly applicable in each EU Member State, however, it provides that EU Member States may introduce further conditions, including limitations which could limit our ability to collect, use and share personal data (including health and medical information), or could cause our compliance costs to increase, ultimately having an adverse impact on our business.

imposes accountability and transparency obligations regarding personal data.

The GDPR imposes accountability and transparency obligations regarding personal data.

We are also subject to EU rules with respect to cross-border transfers of personal data out of the EU and EEA.

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Violation of the federal Anti-Kickback Statute may also constitute a false or fraudulent claim for purposes of the federal civil False Claims Act.

Actions under the civil False Claims Act may be brought by the Department of Justice or as a qui tam action by a private individual in the name of the government.

Actions under the civil False Claims Act may be brought by the Department of Justice or as a qui tam action

by a private individual in the name of the government.

Many states also have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

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Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

In the EU, pricing and reimbursement schemes vary widely from country to country.

Some countries provide that products may be marketed only after a reimbursement price has been agreed.

Some countries may require the completion of additional studies that compare the cost effectiveness of a particular product candidate to currently available therapies (so called health technology assessments) in order to obtain reimbursement or pricing approval.

The EU recently adopted Regulation (EU) 2021/2282 on health technology assessment, which provides a framework for Member States to cooperate on health technology assessments at the EU level.

The regulation is directly applicable in all EU Member States which is in a phased period of applicability since January 12, 2025, although pricing will still be determined nationally.

Moreover, at the national level, EU Member States may restrict the range of products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

Member States may approve a specific price for a product or may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.

Other Member States allow companies to fix their own prices for products, but monitor and control prescription volumes and issue

guidance to physicians to limit prescriptions.

Recently, many countries in the EU have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU.

The downward pressure on health care costs in general, particularly prescription products, has become intense.

As a result, increasingly high barriers are being erected to the entry of new products in the marketplace.

Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by various EU Member States and parallel trade (arbitrage between low-priced and high-priced member states) can further reduce prices.

Special pricing and reimbursement rules may apply to orphan drugs.

Inclusion of orphan drugs in reimbursement systems tend to focus on the medical usefulness, need, quality and economic benefits to patients and the healthcare system as for any product.

Acceptance of any medicinal product for reimbursement may come with cost, use and often volume restrictions, which again can vary by country.

In addition, results-based rules of reimbursement may apply.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products, if approved in those countries.

Healthcare Reform

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This included aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect on April 1, 2013, and, due to subsequent legislative amendments, will stay in effect through 2027 unless additional Congressional action is taken.

On January 2, 2013, the American Taxpayer Relief Act was signed into law, which, among other things, further reduced Medicare

payments to several providers, including hospitals and imaging centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

The Biden administration has indicated that lowering prescription drug prices is a priority.

On October 14, 2022, President Biden signed an executive order to lower prescription drug costs for Americans.

In response to this directive, the HHS Secretary announced and the Center for Medicare and Medicaid Innovation is developing three new models intended to lower drug costs under Medicare and Medicaid, including establishing a new approach for administering outcomes-based agreements for cell and gene therapies.

President Biden also signed an executive order on July 9, 2021 affirming the administration’s policy to, among other things, support legislative reforms that would lower the prices of prescription drugs, including by supporting the development and market entry of lower-cost generic drugs and biosimilars, and support the enactment of a public health insurance option.

Among other things, the executive order directs the HHS Secretary to provide a report on actions to combat excessive pricing of prescription drugs, continue to clarify and improve the approval framework for generic drugs and identify and address any efforts to impede generic drug competition, enhance the domestic drug supply chain, reduce the price that the federal government pays for drugs, and address price gouging in the industry.

The executive order also directs the FDA to work with states and Indian Tribes that propose to develop section 804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, and the FDA’s implementing regulations.

The FDA released such implementing regulations on September 24, 2020, which went into effect on November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada.

In response, authorities in Canada have passed rules designed to safeguard the Canadian drug supply from shortages.

On January 5, 2024, the FDA authorized Florida’s Agency for Health Care Administration’s drug importation proposal, the first step toward Florida facilitating importation of certain prescription drugs from Canada.

On January 2, 2013, the American Taxpayer Relief Act was signed into law, which, among other things, further reduced Medicare payments to several providers, including hospitals and imaging centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

The Trump Administration has discussed several changes to the reach and oversight of the FDA, which could affect its relationship with the biotechnology and pharmaceutical industries, transparency in decision making and ultimately the cost and

availability of prescription drugs.

Drug pricing is an active area for regulatory reform at both the federal and state levels, and additional significant changes to current drug pricing and reimbursement structures in the U.S.

could be forthcoming.

It remains unclear how any new legislation or regulation might affect the prices we may obtain for any of our product candidates for which regulatory approval is obtained.

Employees and Human Capital Resources

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Our people, driven by our collaborative, pioneering, and patient-focused culture, propel our business forward, strengthening us for long-term success.

As of December 31, 2023, we had 38 employees, 26 of whom are primarily engaged in research and development activities and 12 in corporate functions.

37 of our employees are employed by us on a full-time basis.

As of December 31, 2024, we had 66 full-time employees, 54 of whom are primarily engaged in research and development activities and 12 of whom are primarily engaged in corporate functions.

58% of our employees have at least one of a Masters, PhD, or MD degree.

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We make available on our website at www.cartesiantherapeutics.com, free of charge, copies of these reports as soon as reasonably practicable after filing or furnishing these reports with the SEC.

Additionally, our Code of Business Conduct and Ethics is available on our website.

The hyperlink to our website is included as an inactive textual reference only, and the information on our website is not incorporated by reference in this Annual Report on Form 10-K or in any other filings we make with the SEC.

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You should carefully read and consider the matters discussed in this Annual Report under the heading “Risk Factors,” which include the following risks:

• We are a development-stage company and have incurred significant losses since our inception.

We expect to incur losses for the foreseeable future and may never achieve or maintain profitability.

• We are a development-stage company, and we expect to incur losses for the foreseeable future and may never achieve or maintain profitability.

• We will need substantial additional funding in order to complete development of our product candidates and commercialize our products, if approved.

If we are unable to raise capital when needed and on terms favorable to us, we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

• We develop our mRNA-based product candidates by leveraging our proprietary technology and our manufacturing platform, RNA Armory®, which is an unproven approach to the treatment of autoimmune disease.

• We develop our mRNA-based product candidates by leveraging our proprietary technology and our manufacturing platform, which is an unproven approach to the treatment of autoimmune disease.

We are early in most of our clinical development efforts and may not be successful in our efforts to build a pipeline of product candidates and develop marketable drugs.

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• We expect to continue to grow our manufacturing capabilities and resources and we must incur significant costs to develop this expertise and/or rely on third-parties to manufacture our products.

• We rely, and expect to continue to rely, on third parties to conduct our clinical trials, and those third parties may not perform satisfactorily, including by failing to meet deadlines for the completion of such trials.

• We rely, and expect to continue to rely, on third-parties, including CROs, to conduct our clinical trials, and those third-parties may not perform satisfactorily, including by failing to meet deadlines for the completion of such trials.

• If we or our licensors are unable to adequately protect our proprietary technology, or obtain and maintain issued patents that are sufficient to protect our product candidates, others could compete against us more directly, which would negatively impact our business.

• We have been in the past and may in the future be subject to stockholder litigation.

• The failure to successfully integrate the businesses of Selecta and Old Cartesian in the expected timeframe would adversely affect the Company’s future results.

• We have identified a material weakness in our internal control over financial reporting and may identify additional material weaknesses in the future or otherwise fail to maintain an effective system of internal controls, which may result in material misstatements of our consolidated financial statements or cause us to fail to meet our periodic reporting obligations.

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