REGULATORY INSTITUTION CONSENT FORM TO VOLUNTEER IN A HUMAN RESEARCH STUDY

Title of Study:	A Phase 2, randomized, open-label, controlled study to evaluate the efficacy and safety of rapcabtagene autoleucel versus comparator in participants with severe refractory idiopathic inflammatory myopathies
Sponsor	Sponsor Pharmaceuticals Corporation
Protocol Number:	Sponsor: CYTB123451 Local: PRO00012345
Study Doctor:	John Doe, M.D.
Telephone:	123-123-1234 or 111-111-1234 (24 Hours)
Address:	1243 John Doe St. Suite 1001 Medical, State 12345 USA

Participant’s Name:

Participant ID Number:

This is an informed consent and authorization form for a research study. The first part of this form is a summary of the key information about this study to help you decide if you want to join the study. More detailed information about the study will be explained later in the form.

Please treat the information provided in this document as confidential. However, this information may be shared with anyone who you may need to help you decide whether to join the study or help you to decide if you wish to leave the study in the future.

Key Information

You are asked to be in this study because you have myositis (severe refractory idiopathic inflammatory myopathy) and may be eligible to participate in this research. Myositis is a disease where the body’s immune system mistakenly attacks the muscles, causing symptoms such as weakness or difficulty moving. In some cases, it can affect other parts of the body, including the lungs, making it harder to breathe. Myositis can be difficult to control with current treatments, and not everyone responds well. This study is different from standard care because it is testing an investigational treatment called YTB323, which is not part of routine medical care for myositis. YTB323 or rapcabtagene autoleucel (is a type of gene therapy called CAR-T cell therapy). CAR-T therapy, which stands for chimeric antigen receptor, involves modifying your own immune cells (T cells) to target and destroy B cells, which are believed to contribute to myositis.

The goal of this research is to find out whether YTB323 is safe and whether it can help people with myositis. The study will also compare YTB323 to several currently available myositis treatments to see how they differ in safety and how well they control the disease.

YTB323 is currently being studied in people with blood cancer and in people with systemic lupus erythematosus (SLE). As of February 20, 2025, 204 participants with blood cancer had been treated with YTB323, and as of January 21, 2025, 21 participants with SLE had been treated with YTB323. This is the first time YTB323 is being studied in people with myositis, and it is not approved as a treatment for myositis. Because of this, it is not known if YTB323 will work for you or what side effects you personally may experience. Your condition may improve, it may stay the same, or it may get worse.

Because YTB323 is investigational, it is only available in research studies like this one and is not an approved standard treatment for myositis.

The study treatment may or may not help your symptoms, but what is learned in this study may help treat other people with myositis in the future. Taking part in this research study may not benefit you directly.

This study is not a substitute for your regular medical care. You should continue to see your regular doctors for your usual health needs.

Instead of taking part in this study, you may choose to receive:

• Standard treatments, such as rituximab, cyclophosphamide, mycophenolate mofetil (MMF) or mycophenolic acid (MPA), tacrolimus, or other therapies your doctor recommends for myositis
• Other investigational therapies, if they are available to you outside this study
• No study treatment, and instead receive comfort-focused care (also called palliative care) to help you stay as active and comfortable as possible

Your study doctor and/or your personal doctor can talk with you about the risks and benefits of these options. In all cases, you will continue to receive appropriate medical care.

Participation in this study is completely voluntary. “Voluntary” means it is your choice. Taking part in a research study is not part of your routine, standard care. If you choose not to join the study, or if you decide later to leave the study, you can still receive care at Regulatory Institution with no penalty and no loss of benefits.

Before choosing to take part, you should talk with the study team or study doctor about any questions or concerns you have, including possible side effects, how often you will need to come to the clinic, potential costs or reimbursement, and how much time the study is likely to take.

There may be reasons you do not want to be in this study, such as:

• The study lasts up to 5 years, and if you receive YTB323 you will also be asked to join a long-term safety follow-up for 15 years after the YTB323 infusion.
• You will have frequent study visits for physical exams, blood and urine tests, heart tests (ECG and cardiac imaging), lung tests (spirometry), questionnaires, and sometimes optional lung imaging (HRCT) if your lungs are affected by myositis.
• If you are in the group that receives YTB323 (either initially or after switching from the comparator group), you will need to:
• Stop or reduce some of your current myositis medications (washout), which may increase the risk that your disease will flare or worsen and could cause temporary or permanent organ damage.
• Undergo a procedure called leukapheresis to collect your cells, which can cause side effects like lightheadedness, dizziness, nausea, feeling cold, tingling in the lips or fingers, shortness of breath, sweating, and local catheter-site reactions (itching, pain, bruising, bleeding, infection); very rarely, serious events like heart failure, fainting, or nervous system problems may occur.
• Receive a 3-day course of low-dose chemotherapy (lymphodepletion with fludarabine and cyclophosphamide) before YTB323. This can cause side effects such as nausea, vomiting, hair loss, fever, skin rash or itching, loss of appetite, diarrhea, headache, muscle pain, weakness, dizziness, bruising, mouth sores, low blood counts, and increased risk of infections. Rare side effects include infertility, bladder irritation or bleeding, increased risk of some cancers, vision problems, and neurological effects like confusion, agitation, or seizures.
• Receive a single infusion of YTB323 and then possibly experience side effects seen with YTB323 and similar CAR-T therapies, such as fever, chills, low blood pressure, trouble breathing, flu-like symptoms, dizziness, confusion, agitation, trouble speaking or understanding speech, delirium, seizures, infections, low red blood cells, low hemoglobin, low white blood cells, low platelets (bruising or bleeding), weakness, and paralysis. Some of these side effects may be serious or require a longer hospital stay. YTB323 may stay in your body for a long time and cause delayed side effects.
• If you are randomly assigned to the comparator arm and never switch to YTB323, you will not have the risks of leukapheresis, lymphodepletion, or YTB323 itself, but you will still have the risks of your chosen comparator treatment and the risks of study procedures.

This research is being funded by Sponsor (the sponsor).

Regulatory Institution may benefit from your participation and/or what is learned in this study.

How long will the research last and what will I need to do?

You are expected to be in this research study for about 5 years.

Some people who receive the study cell therapy YTB323 may also be asked to join a separate long-term safety follow-up study so their health can be checked for up to 15 years after they receive YTB323.

During the study, you will be asked to:

• Come to the clinic regularly for study visits over the 5-year study period.
• Answer questions about your health, medical history, and the medicines you are taking.
• Have physical exams and checks of your vital signs (such as temperature, blood pressure, heart rate, breathing, and oxygen level).
• Give blood and urine samples for routine safety tests and research tests.
• Have heart tests such as an electrocardiogram (ECG) and heart ultrasound (echocardiogram).
• Have breathing and lung function tests, and in some cases lung imaging (chest scans) if you have lung involvement from your myositis.
• Complete questionnaires about your myositis symptoms, how you feel, and how your disease affects your daily life.
• Use an electronic symptom diary at certain times to record symptoms such as pain, fatigue, and sleep problems, and use a paper diary to record your corticosteroid doses.

• If you are in the YTB323 arm (or later switch to YTB323):
• Stop or reduce (“wash out”) some of your current myositis medicines as instructed.
• Have a procedure called leukapheresis, where some of your white blood cells (T cells) are collected to make YTB323.
• Receive 3 days of low-dose chemotherapy (lymphodepletion) to prepare your body for the YTB323 cells.
• Receive a one-time infusion of YTB323 through a vein.
• Stay in the hospital for at least 2 weeks after the YTB323 infusion, then stay within about 2 hours travel distance of the study site for another 2 weeks, and return for frequent follow-up visits (you should not drive for 8 weeks after YTB323).

• If you are in the comparator arm:
• Receive one of the comparator medicines chosen by your Study Doctor (rituximab, cyclophosphamide, mycophenolate mofetil / mycophenolic acid, or tacrolimus).
• Come for regular follow-up visits with similar exams, blood and urine tests, heart and lung tests (as needed), and questionnaires.
• If your myositis is not well controlled after at least 1 year and before Year 4, you may have the option to switch to YTB323, which would then involve the YTB323-related procedures described above.

Throughout the study, your Study Doctor will review your results, monitor your safety, and may order additional tests if needed to check on your health.

The following parts of the study are optional and will only be conducted with your separate consent, which may require an additional signature page or a separate consent form:

• Genetic research
• Optional in-trial interview
• Optional HRCT assessment for selected participants (listed twice, so I kept one)
• Optional consent for additional research
• Optional consent for activities that may be done outside of the study site
• Exceptional release purposes

Detailed Information: The following is more detailed information about this study in addition to the information listed above.

Who can I talk to?

If you have questions, concerns, or complaints, or think the research has hurt you, talk to the research team at: 281-222-9983.

This research has been reviewed and approved by an Institutional Review Board (IRB - a committee that reviews research studies). You may talk to the Regulatory Institution Institutional Review Board (IRB-- a group of doctors, researchers, and community members that is responsible for protecting study participants and making sure that all research is safe and ethical) at any time by calling them at 346-356-1400 or emailing them at IRB@Medical.org if:

• You cannot reach the research team.
• Your questions, concerns, or complaints are not being answered by the research team.
• You want to talk to someone besides the research team.
• You have questions about your rights as a research participant.
• You want to get information or provide input about this research.

How many people will be in the research?

About 123 participants with myositis will take part in this research study worldwide.
About 3 of those participants will be enrolled at Regulatory Institution. All participants in the study will be 18 to 65 years old.

If you do not meet the screening requirements, you will not be able to join the study. If this happens, your Study Doctor can discuss other treatment options with you.

What happens if I say yes, I want to be in this research?

Study overview

YTB323 arm

If you are part of the first group of 6 participants or you are assigned to the YTB323 arm or you are switching from the comparator arm to receive YTB323, then the following applies to you. Before you receive YTB323, you will need to visit the study site to complete the following visits: Screening, Randomization/Baseline, leukapheresis, and lymphodepletion to prepare your body for YTB323 (Section ‘Washout, Leukapheresis, and YTB 323 manufacturing’). After lymphodepletion, you will receive a one-time infusion of YTB323. Once you have received YTB323, you will need to stay in the hospital for at least 2 weeks for close monitoring of side effects. After you are discharged, you will need to stay close to the study site for 2 more weeks, until the end of the 4^th week after you received YTB323. During this time, your total travelling time to reach the study site should not be more than 2 hours and you should not drive. See section ‘YTB323 arm procedures’) for further details. Then, you will continue to be monitored closely for your safety by attending frequent visits until 8 weeks (about 2 months) after you receive YTB323 administration. Then, you will continue in the study for about 5 years.

If you have received YTB323, you will be asked to join a long-term safety follow-up for a total of 15 years after the YTB323 infusion. This long-term follow-up is not part of this 5-year study you are signing this consent for. The graph below shows the outline of the YTB323 therapy.

Figure 1-1 Outline of study for YTB323 arm

* EOS: End of Study

** Long-term Follow-up for a total period of 15 years after YTB323 infusion

Comparator arm

If you are assigned to the comparator arm, then the following applies to you. You will receive comparator treatment, which will be one of the 4 options as outlined above (Section ‘What study treatment will I get?’), as advised by your Study Doctor. If you are not experiencing enough control of your symptoms as determined by your Study Doctor, you may have the option to receive study treatment with YTB323 after Year 1 but before Year 4 Your Study Doctor will discuss the safety requirements with you. The graph below shows an outline of the comparator treatment.

Figure 1-2 Outline of study for comparator arm

* EOS = End of Study

** Long-term Follow-up for a total period of 15 years after YTB323 infusion

What study treatment will I get?

If you are part of the first group of participants to enter the study, you will receive a one-time administration of YTB323. Once the first group, which consists of at least 6 participants has received YTB323 and the Sponsor and your Study Doctor confirm there are no unexpected safety concerns, the study will proceed. It is possible that the study is stopped before all participants in the first group 6 participants are enrolled. If you have agreed to participate in this study and the study is stopped before you receive the planned YTB323 infusion, your Study Doctor will discuss other treatment options with you.

The second group of about 117 participants to be included in the study will be randomly (by chance) assigned to receive either YTB323 or a comparator treatment:

· YTB323: You have a 66% possibility (2 out of 3 participants) of getting this treatment. The treatment will be given intravenously (through a needle and tubing inserted into your vein) as a one-time administration.

· Comparator treatment: You have 33% possibility (1 out of 3 participants) of getting one of the 4 comparator treatment options available.

If you are assigned to the comparator arm, your Study Doctor will decide which comparator treatment is best for you from the following treatment options:

1. Rituximab

2. Cyclophosphamide

3. Mycophenolate Mofetil (MMF) or Mycophenolic Acid (MPA)

4. Tacrolimus

YTB323 is a chimeric antigen receptor (CAR) T cell therapy, which is a type of gene therapy/immunotherapy. CAR-T cell therapy involves collecting and using the participant’s own immune cells, specifically their T cells, to treat their disease. T cells are a type of white blood cell that are also known as T lymphocytes. After collection, the participant’s T cells are sent to the manufacturer’s (Sponsor) laboratory, where they are genetically modified to make them able to fight and destroy another type of immune cells called B cells, which are believed to contribute to myositis.

Before the collection of your T cells, you may be required to stop taking your current myositis medication, this is called a washout from your current medication. See Section ‘What to expect at and between study visits?’ for more details on the washout process. If you are currently being treated with corticosteroids, your dose will be gradually reduced (this is called tapering) to help with successful collection of your T cells. To collect T cells, you will undergo a procedure called leukapheresis, where your blood will be collected, and a machine will separate your T cells that will be sent to the manufacturer. After removal of the T cells, your blood (minus the extracted T cells) will be infused back into you. After leukapheresis and before you receive YTB323, you will undergo a lymphodepleting treatment, which is a combination of two chemotherapy medications, called fludarabine and cyclophosphamide, that are given at low doses once daily for 3 days.

If you are randomly assigned to the comparator arm, your Study Doctor will discuss with you and advise which comparator treatment would be the best for you. If you are enrolled in this arm and are not experiencing acceptable control of your symptoms, as determined by your Study Doctor, you might be eligible to receive treatment with YTB323 after 1 year,

but before Year 4. Your Study Doctor will review the safety requirements with you.

Both you and your Study Doctor will know which treatment you are getting. However, some of the study staff, who will be evaluating your myositis during the study, will not know which treatment you are getting, these are called “Blinded Assessors”. The Blinded Assessor will be performing assessments to record your myositis disease level beginning at the Screening visit and for the rest of the study.

It is important that you do not tell the Blinded Assessor(s) which study treatment (YTB323 or comparator treatment) you are receiving to ensure the results of the study are not biased. Your Study Doctor will tell you who the Blinded Assessor(s) are at the study site. Please do not share with the Blinded Assessor(s) any information about your leukapheresis, lymphodepletion, hospital stay for YTB323 administration, dose of corticosteroids you might be taking for myositis, what you think about your study treatment, or anything that might indicate which study treatment you are receiving.

Rescue Treatment

If you think your myositis is getting worse, immediately tell your Study Doctor. Your Study Doctor will discuss this with you and may give you another treatment called “rescue treatment”. A rescue treatment is a medication that is used, when needed, to reduce the severity of your disease if YTB323 or the comparator treatment are not helping enough.

Study visits

What to expect at and between study visits?

You will be in this research study for about 5 years. At any time, your Study Doctor may contact your Personal Doctor to get more information about your health, if you allow this. Based on the treatment arm you are assigned to, you may need to see additional doctors while participating in this study such as a hematologist/oncologist. A hematologist/oncologist specializes in blood diseases and/or cancer and will work with your Study Doctor to oversee the leukapheresis, lymphodepletion, and YTB323 administration.

If you have any questions about any of these activities, please speak with your Study Doctor.

Here is a summary of what may happen during your study visits.

Screening Tests

Signing this consent form does not mean you are automatically in the study.

If you agree to participate in the study by signing this consent form, your Study Doctor will have up to 6 weeks to complete certain tests to see if you can participate in the study. This is called a “screening period”.

· Your Study Doctor will ask you some questions about your health, your medical history, about any medications you have been taking and your vaccination status.

· It is important to note that the study treatment (YTB323) can increase your risk of infections, including those that can be prevented with vaccinations.

· Your Study Doctor will talk to you about your vaccination history. As your immune system may not be strong enough to fight off infections, your Study Doctor or a specialist may recommend certain vaccines to help protect you. Not all infections have vaccines, but for those that do, you will be offered them when you join the study and whenever it is needed while you are in the study.

· Your Study Doctor will do a physical exam including a measurement of your height, weight, and vital signs (body temperature, blood pressure, heart rate, pulse oximetry, respiration rate).

· Your Study Doctor will check your heart function by ordering an ECG and cardiac imaging (ECHO). More details on these two tests are in Section ‘Cardiac Assessments’.

· A urine sample will be collected for urinalysis.

· Blood will be collected for standard and research laboratory testing. Tests will also be done to detect different infections including hepatitis B and C, HIV (AIDS), and tuberculosis. In the event that any of these tests are positive, your Study Doctor will offer you information and advise you on the next steps. This is to allow for any additional monitoring and treatment, if necessary.

· If you are a female who is able to become pregnant, your blood will be tested to see if you are pregnant.

· You will receive a device (similar to an iPhone) to use as an electronic symptom diary to record symptoms of pain, fatigue, or sleep problems during specific times in the study while at home. The study staff will train you on how to use this electronic symptom diary and will tell you when you will need to use it.

· The study staff will call you with a reminder to start completing the electronic symptom diary to record symptoms of pain, fatigue, and sleep problems daily for 7 days before the Randomization/Baseline visit.

· You and your Study Doctor will complete questionnaires to assess your myositis disease level and overall health status.

· Your myositis disease level will be checked using tests for muscle weakness such as manual muscle testing of 8 muscles (called MMT-8) and muscle endurance using a test called functional index 3 (FI-3) which will check endurance of 3 muscles: neck, shoulder, and hip.

· You may have additional tests done to confirm that your myositis is still active. These tests may include magnetic resonance imaging (MRI) of your muscles, a muscle biopsy, or electromyography (EMG), which measures the electrical activity in response to a nerve’s stimulation of the muscle.

· Your Study Doctor will check your lung function by ordering two tests: a diffusing capacity for carbon monoxide (also called DLCO test) to measure how much gas moves from your lungs to your blood when you inhale, and a spirometry test which measures how much air you can breathe in and out of your lungs. These tests might be done in a different location from your study site.

There are 2 optional procedures which your Study Doctor may offer closer to your anticipated enrollment or randomization date, depending on your country and your specific myositis disease.

· If you agree to participate in an optional in-trial interview, it will be scheduled within 10 days prior to Randomization/Baseline visit. This interview will be used to understand your experience with myositis. This is your chance to have your voice heard about your condition. This will require that you sign a separate, additional informed consent.

· If you enter the study after the first group of participants has already been enrolled and have a diagnosis of interstitial lung disease (also called ILD), you may be given the option to have high resolution computed tomography (HRCT) images taken of your lungs to help further understand the effects of the study treatment on the lungs. This will require that you sign a separate, additional informed consent.

Your Study Doctor will discuss if there is any need for you to make any changes to your current treatment(s), including your medication to treat your myositis, before continuing with the next study visit.

Your Study Doctor will review the screening results to check if you meet the requirements (are eligible) to participate in the study. If the screening results do not meet the study requirements, you cannot take part in the study.

Randomization / Baseline

If you meet the study requirements based on the above screening requirements, you will continue with the Randomization visit, which is sometimes also called Baseline visit. Randomization means that a computer will randomly (by chance) assign you to one of the two possible treatment arms.

There is no randomization step for participants who are part of the first group, as they will all receive YTB323.

The second group of approximately 117 participants will be randomized to receive either YTB323 or a comparator treatment. About two thirds of participants will be assigned to YTB323 and one third will be assigned to the comparator (see Section ‘What study treatment will I get?).

Prior to randomization/baseline, you will complete the following assessments:

· Your Study Doctor will do a physical exam including a measurement of your weight, and vital signs (body temperature, blood pressure, heart rate, pulse oximetry, respiration rate).

· You and the Blinded Assessor (study staff who shouldn’t know which study treatment you are receiving) will complete questionnaires to assess your myositis disease level and overall health status.

· The Blinded Assessor will also perform tests for muscle weakness such as manual muscle testing of 8 muscles (called MMT-8) and muscle endurance using a test called functional index 3 (FI-3) which will check endurance of 3 muscles: neck, shoulder and hip. More details about the Blinded Assessor can be found in Section ‘What study treatment will I get?

· An ECG will be performed.

· A urine sample will be collected for urinalysis.

· Blood will be collected for standard and research laboratory testing. This may also include an optional blood sample for DNA that will be offered in a separate consent form.

· If you are a female who is able to become pregnant, your blood will be tested to see if you are pregnant.

· If you have a diagnosis of interstitial lung disease, you will undergo a spirometry test which measures how much air you can breathe in and out of your lungs.

· If your Study Doctor confirms that you still meet all of the study requirements from the assessments above, you will be randomized. The participants who are part of the first group will not be randomized and will receive YTB323. If you are going to receive YTB323, the study staff will provide instructions on how to washout your current myositis medication and schedule leukapheresis.

· If you are randomized to receive a comparator treatment, you may begin the treatment on this day or shortly afterwards. A description of follow-up visits for participants in the comparator arm begins in Section ‘Follow-up visits’.

Washout, Leukapheresis, and YTB323 manufacturing

The medication washout, leukapheresis, and YTB323 manufacturing might take around 2 to 4 weeks.

If you are part of the first group of participants or if you are randomized to the YTB323 arm or if you are switching over from the comparator arm to receive YTB323 infusion you may be required to stop taking (or washout) your current myositis medication and to gradually reduce your dose of corticosteroids. This will improve the chance of a successful collection of your T cells. The duration of the washout period is determined by which specific medication you are on. There is a risk that your myositis may get worse. This potential disease worsening may be severe and result in damage to your organ(s) that may be temporary or permanent. Please talk to your Study Doctor to learn more about the possible risks related to your health condition. Once the leukapheresis process is completed, your Study Doctor may provide therapy with steroids or with another medication. There is a second washout before lymphodepletion (see Section ‘Lymphodelption’) and your Study Doctor will tell you again when to stop using the myositis medications and for how long. Your Study Doctor will provide instructions on this.

When your washout is complete, you will be invited for your next visit which will last approximately 4 to 7 hours. In some instances, more than one visit may be required to complete this procedure if your T cell blood count is on the lower range.

During this visit, your blood will be taken to collect your T cells. This procedure is called leukapheresis.

Prior to starting leukapheresis, if you are a female who is able to become pregnant, you will need to have a blood pregnancy test. If you are pregnant, you cannot continue in the study. Blood will be collected for standard and research laboratory testing and vital signs will also be collected to check if it is still safe for you to undergo leukapheresis.

The collected T cells will be shipped to an outside facility to manufacture YTB323. During manufacturing, T cells taken from your body are genetically modified to make them capable of destroying your B cells (the cells that may contribute to your myositis).

It is important to understand that meeting study eligibility and undergoing leukapheresis does not guarantee that you will receive YTB323. There is a low possibility that during the transportation of the cells from the study site to the manufacturing site, your cells may become damaged, lost, or mislabeled. In addition, after manufacturing, the modified T cells will be inspected to ensure they are acceptable to be used for administration. If the quality of the cells is not deemed acceptable (as defined by Sponsor) for administration, YTB323 can be re-manufactured (which may or may not require another leukapheresis). This means that more time may be needed before you are able to receive YTB323. However, under rare circumstances, your Study Doctor, in agreement with your hematologist/oncologist, may conclude that the anticipated benefit of infusing YTB323 which did not pass all of the required tests as defined by Sponsor outweighs the risk(s) and they may request to give it to you if allowed by local regulations. This will require that you sign a separate, additional informed consent. In addition, during the manufacturing, T cells taken from your body may not grow properly. If this happens you will not be able to receive YTB323 treatment and may be asked by your Study Doctor to consider a second attempt at manufacturing with a new collection of T cells from your body (another leukapheresis).

In case your T cells cannot be used for manufacturing of YTB323 or the manufactured YTB323 cannot be used for your treatment, Sponsor will retain these materials and handle them in accordance with the local laws and Sponsor policies.

Your Study Doctor may decide to treat you with corticosteroids or other medications to control your disease while your T cells are being manufactured into YTB323. Your Study Doctor will inform you about potential side effects of these medications.

If you are randomized to the comparator arm, you will not undergo leukapheresis and YTB323 manufacturing, unless you switch to YTB323 treatment. Your Study Doctor will discuss if you meet the criteria for switching to YTB323.

Lymphodepletion

The next step after leukapheresis is a procedure called lymphodepletion, which will take 3 days. Once it is confirmed that the manufactured YTB323 is available at the study site and ready to be infused, you’ll get treated with low doses of chemotherapy as part of the lymphodepletion procedure. This will help to get your body ready so that the CAR-T cells can work as best as possible. As part of the lymphodepleting therapy, you will receive fludarabine and cyclophosphamide intravenously once daily for 3 days.

You might be asked to stay in the hospital while you are receiving lymphodepleting therapy. In this case, your Study Doctor will let you know if and for how long you will need to stay in a hospital.

The purpose of lymphodepletion is to reduce the number of your T cells. This procedure helps by creating an optimal environment for the modified CAR-T cells (YTB323) to remain in your body.

Prior to starting lymphodepletion therapy, your Study Doctor will check if it is safe for you to receive it:

· Your blood and urine samples will be collected for standard and research laboratory testing. Your Study Doctor will also check if you have any new infections and may do some additional testing. If you have an infection, you will receive lymphodepletion after complete recovery.

· If you are a female who is able to become pregnant, your blood will be tested to see if you are pregnant prior to lymphodepletion. If you are pregnant, you cannot continue in the study.

· Your Study Doctor will do a physical exam including a measurement of your weight and vital signs (body temperature, blood pressure, heart rate, pulse oximetry, respiration rate).

During Days 2 and 3 of lymphodepletion therapy, your Study Doctor will do a physical exam and research blood samples will be collected just before start of lymphodepletion and 30 minutes after it is completed.

If you are randomized to the comparator arm, you will not undergo lymphodepletion, unless you switch to YTB323 treatment. Your Study Doctor will discuss if you meet the criteria for switching to YTB323.

Study Drug (YTB323 administration)

The next step after lymphodepletion is YTB323 administration, which should occur 2 to 6 days after completing lymphodepletion.

Before YTB323 administration, your Study Doctor will check if it is still safe for you to receive it:

· Your Study Doctor will do a physical exam including a measurement of your weight and vital signs (body temperature, blood pressure, heart rate, pulse oximetry, respiration rate).

• Your blood and urine samples will be collected for standard and research laboratory testing.
• If you are a female who is able to become pregnant, your blood will be tested to see if you are pregnant prior to the administration. If you are pregnant, you cannot continue in the study.
• An ECG will be performed.
• Your Study Doctor will also check if you have any new infections and maybe do some additional testing.

Once your Study Doctor determines that it is safe to continue, you will receive the YTB323 infusion. Prior to YTB323 administration, you will receive medications to reduce potential side effects such as fever and allergic reactions. You will receive YTB323 intravenously (through a needle and tubing inserted into your vein).

Measurement of your body temperature, blood pressure, heart rate, pulse oximetry, respiration rate will be done before, during, and after YTB323 infusion, approximately every 15 minutes for the first hour and then every hour for the next two hours. Monitoring may continue until these measurements are stable.

After you receive the YTB323 infusion, you will need to stay in the hospital for at least 2 weeks. Hospitalization is needed so that your Study Doctor can continue to monitor you closely by repeating the tests mentioned above and be able to immediately treat any potential side effects (see Section ‘Are there any side effects (risks) if I join this study?’). During hospitalization, your Study Doctor will do regular physical examinations, check vital signs, collect blood samples for standard and research tests and perform periodic ECGs. It is possible that you may need to stay in the hospital longer than 2 weeks.

You will be discharged from the hospital 2 weeks after YTB323 administration and you will be instructed to remain near the study site (within 2 hours of total travel time) for an additional 2 weeks (i.e., until 4 weeks after YTB323 administration), as some of the side effects may require immediate care by your Study Doctor. You should not drive during the 8 weeks after YTB323 infusion. Your Study Doctor will provide you with the information you need to recognize these side effects and to determine when to call him/her. See Section “If you received YTB323 treatment” for further details. After you have been discharged from the hospital, you will also be asked to return to the study site three more times over the next 2 weeks (specifically on Days 17, 22, and 28 after YTB323 administration) for a physical examination, checking of vital signs, standard and research blood testing, urine collection and ECG.

Follow-up visits

If you received YTB323, you will be closely monitored for any side effects during hospitalization and frequent visits until 8 weeks have passed since YTB323 administration. After that, the visit frequency will be reduced to monthly until Week 24. After Week 24, the visit frequency is reduced to every 12-14 weeks until Week 76, then approximately every 6 months till the end of study. The final visit will be at Week 260 (5 years after your enrollment/randomization).

If you are assigned to the comparator arm, you will return to the study site for visits at Week 2 and Week 4, then monthly until Week 24. After Week 24, the visit frequency is reduced to every 12-14 weeks until Week 76, then approximately every 6 months till the end of study. The final visit will be at Week 260 (5 years after your Randomization visit).

During these visits:

· You will be given a paper diary to collect information about your corticosteroid use and doses. You will need to bring this diary to every visit, and it will be reviewed by the study staff to check if you are using corticosteroids correctly and reducing the dose as instructed.

· At every visit, your Study Doctor will do a physical exam including a measurement of your weight and vital signs (body temperature, blood pressure, heart rate, pulse oximetry, respiration rate).

· At every visit, blood and urine samples will be collected for standard laboratory testing. At some visits, samples will be collected for research laboratory testing and to assess how much YTB323 is in your body for participants who received YTB323.

· An ECG will be performed at some visits.

· Immunizations or vaccinations will be regularly discussed with your Study Doctor, to help protect you against infections. Your Study Doctor will refer to or update your vaccination/immunization records during the time of your visit. If the visits are more than 3 or 6 months apart, the study staff may reach you via phone call for this discussion.

· If you are a female who is able to become pregnant, your urine will be tested to see if you are pregnant. When the visits are more than 1 month apart, you will be asked to do pregnancy tests at home. Your Study Doctor will provide you with the pregnancy tests. In case of a positive result at home, you must immediately contact your Study Doctor.

· You and the Blinded Assessor (study staff who shouldn’t know which study treatment you are receiving) will complete questionnaires to assess your myositis disease level and overall health status at some visits.

· The Blinded Assessor will also perform tests for muscle weakness (MMT-8) and muscle endurance (FI-3) at some visits.

· If you entered the study with a diagnosis of interstitial lung disease, you will undergo a spirometry test which measures how much air you can breathe in and out of your lungs.

· Your Study Doctor will tell you when you need to complete the electronic symptom diary during the study. The electronic diary will also have reminders for when you should be using it. Study staff will call you with a reminder to start using the diary.

· If you agreed to participate in the optional in-trial interview, it will be conducted again at Week 52. If you end the study before Week 52, the optional interview will still be offered to you at the time of your discontinuation.

· If you agreed to participate in the optional HRCT assessment and had HRCT image taken at Screening, a follow-up image will be taken at Week 52.

Additional assessments might be performed if your Study Doctor deems them necessary to monitor your condition.

End of study visit

The end of study visit will take place approximately 5 years after YTB323 administration, or after randomization to the comparator arm. If you switch from the comparator arm to receive YTB323 treatment, then the end of study visit will occur after a minimum of 1 year or up to 4 years after the YTB323 infusion.

During this visit:

· Your Study Doctor will do a physical exam including a measurement of your weight and vital signs (body temperature, blood pressure, heart rate, pulse oximetry, respiration rate).

· An ECG will be performed.

· Blood and urine samples will be collected for standard and research laboratory testing and to assess how much YTB323 is in your body for participants who received YTB323.

· If you are a female who is able to become pregnant, your blood will be tested to see if you are pregnant.

· You and the Blinded Assessor (study staff who shouldn’t know which study treatment you are receiving) will complete questionnaires to assess your myositis disease level and overall health status.

· The Blinded Assessor will also perform tests for muscle weakness (MMT-8) and muscle endurance (FI-3).

· Study staff will call you with a reminder to start using the electronic symptom diary daily for 7 days prior to this visit.

· If you entered the study with a diagnosis of interstitial lung disease, you will undergo a spirometry test which measures how much air you can breathe in and out of your lungs.

Additional assessments might be performed if your Study Doctor deems them necessary to monitor your condition.

Long-term safety follow-up period

All participants treated with YTB323 will be followed for a total of 15 years after YTB323 administration. You may be asked to join a long-term safety follow-up study which includes onsite follow-up visits and phone follow-up visits. This is required as part of the 15-year monitoring for potential side effects, refer to Section ‘Are there any side effects (risks) if I join this study?’ You will be asked to sign a different informed consent form for the long-term safety follow-up study.

If you are assigned to the comparator arm and do not switch to YTB323 treatment, you will not need to participate in the long-term safety follow-up after this study.

More information about some of your assessments

Blood sampling

During this study, your blood samples will be collected at several timepoints, as outlined above. After signing this consent form, approximately 67 mL (around 5 tablespoons) of blood will be collected at Screening and Randomization/Baseline. This is applicable to both participants receiving YTB323 and the comparator.

YTB323 arm:

· Approximately 368 mL blood (approximately 1.5 cups) will be collected during leukapheresis, YTB323 manufacturing, lymphodepletion, YTB323 infusion and up until 27 days after YTB323 infusion.

· Approximately 790 mL of blood (less than 3 cups) will be collected in total for the remainder of the 5-year study from Day 28 after YTB323 infusion until End of Study (5 years after YTB323 administration).

Comparator arm:

· After randomization, approximately, 629.5 mL (little more than 2.5 cups) of blood will be collected from Week 2 until End of Study visit (up to 5 years).

Additional blood may be collected in case of any findings which would require any extra follow-up analysis to ensure your safety.

Leukapheresis

In preparation for leukapheresis, two needles (of the same size as those used when donating blood) will be placed in your veins near each elbow and connected to a machine that will process a portion of your blood. During the procedure, your blood will flow from one arm vein to the machine and back to the other arm. The leukapheresis machine will remove some of your white blood cells (specifically, the T cells that will be used to manufacture YTB323) and will return your blood (minus the T cells) to your body. Sometimes, a single large catheter, called a central line, is placed in the neck or under the collar bone and may be used for the leukapheresis procedure instead of using intravenous lines in the arms. Your blood is prevented from clotting within the tubing of the machine by adding a chemical called citrate. Some additional fluid (“saline”) will also be added to your blood. The compound citrate may cause symptoms that include tingling in your lips and fingers. If this occurs, you will be given some calcium to reverse this effect. The additional fluid (saline) will have no effect on you. Your pulse, blood pressure and body temperature will be checked before and after the procedure. You will be asked to report any new signs of symptoms (e.g., lightheadedness, tingling in lips or extremities, shortness of breath, etc.). The leukapheresis procedure will last approximately 3 to 6 hours per session. More than one session may be needed to collect the required number of cells. The total time it takes to perform the leukapheresis varies from person to person. At the end of the leukapheresis procedure, you will be monitored for about 1 hour. Monitoring may last longer and will depend on the guidelines of the institution performing the procedure. For eventual risks and inconveniences, please refer to Section ‘Risk associated with procedures’.

This study includes a research component to discover a possible link between the characteristics of your T cells removed during leukapheresis and your body's response to different treatments. Following leukapheresis, a sample of the material obtained from the procedure will be collected and stored for research analyses. Sponsor will also use any remaining manufactured YTB323 cells for research purposes and for improving the YTB323 manufacturing process.

If you are in the comparator arm, you will not undergo leukapheresis, unless you switch to YTB323 treatment. Your Study Doctor will discuss if you meet the criteria for switching to YTB323.

Blood and urine collections for research laboratory testing

Cellular kinetics: Cellular kinetics assess how much YTB323 is in your body at different times after treatment. The purpose of collecting and analyzing these blood samples is to understand what is happening to YTB323 in your body. These samples will be taken at scheduled time points throughout the study. This applies only if you have received YTB323.

Immunogenicity: As a response to YTB323 therapy, your body may produce antibodies that attach to YTB323, or T cells that are activated by YTB323. An antibody is a special protein in the blood that your body produces to help fight substances that your body recognizes as unknown, such as bacteria, viruses, and other foreign substances that get into your blood. T cells are immune cells that help fight bacteria and viruses. It is possible that these antibodies or activated T cells could reduce how effective YTB323 therapy is and so, you will be asked to provide blood samples that will be tested for these specific antibodies and T cells. The results of these tests will be used to better understand your response to YTB323 therapy and ensure your safety. This applies only if you have received YTB323.

Biomarkers: To try to understand what effect YTB323 or comparator therapy is having on your disease, and to better understand the disease and autoimmunity, biomarkers are also included in this study. Biomarkers are important biological ‘indicators’ which can be measured from biological samples collected during the study, such as blood and urine samples. Biomarker samples will be collected before you start either YTB323 or comparator treatment and then at various times afterwards. Some biomarker analyses involve studying your blood cells, and these biomarker assessments include examining the level of genetic information in these cells. Your samples may also be used to measure proteins that may be related to your disease or affected by the treatment. Your samples may also be used to develop a new or improved biomarker test.

Optional Genetic testing: The study also includes an additional, optional blood DNA sampling that will be offered in a separate consent form. Declining to participate in the optional DNA testing will in no way affect your ability to participate in the main research activity.

Patient-Reported Outcome measures (PROs)

PRO is another name for the different questionnaires that will be completed by you during the study at the study site using a tablet similar to an iPhone. These will include questionnaires to assess your overall health status, level of myositis, impact of myositis on your daily life and symptoms of fatigue. Participants who enter the study with a diagnosis of interstitial lung disease will complete questionnaires related to symptoms and impact of that condition.

Your Study Doctor and study staff will check your responses for completeness to make sure that you are not missing any responses. If you experienced any discomfort, unusual symptoms or medical problems, please always report these directly to your Study Doctor/study staff.

At several timepoints during the study, you will also be using an electronic symptom diary daily for 7 days to report symptoms of pain, fatigue, and sleep difficulties.

There is also an optional participant in-trial interview and more details are provided in
Section ‘Optional in-trial Interviews’.

Cardiac assessments

Electrocardiogram (ECG)

An electrocardiogram is a test that measures and records the electrical activity of the heart. It is a simple and non-invasive procedure. In order to obtain an ECG, small patches called "electrodes" will be placed over areas of your chest, your arms, and your legs. The electrodes will then be attached to the ECG machine which records the information as the procedure takes place. The electrodes are harmless and just record the electrical activity of your heart. Please ask your study staff if you want more details of this procedure.

Echocardiogram (ECHO)

A cardiac imaging procedure, known as ECHO, will be performed during screening. An ECHO is non-invasive examination used for the assessment of the function and structure of the heart. It uses ultrasound (high-frequency sound waves) from a hand-held wand placed on your chest to take pictures of your heart’s valves and chambers. This helps evaluate how well your heart is working.

Lung function assessments

Spirometry is a lung function test that measures how much air you can breathe in and out of your lungs. It also measures how easily and quickly you can exhale air.

The test involves having a nose clip to block the airflow from the nose whilst breathing through the mouth on a mouthpiece. You will be instructed to breathe normally to begin with, then to take a deep breath to fill the lungs, then blast it out hard and fast to empty all the air out of the lungs. This measurement is then compared with a normal result for someone of your age, height, and sex. If you have any questions, please don’t hesitate to ask the study staff.

Another test to measure your lung function is the diffusing capacity of the lung (DLCO) which measures the transfer of gas from air in the lung to the red blood cells in lung blood vessels. You will be asked to breathe in (inhale) air containing a very small amount of carbon monoxide and a tracer gas, such as methane or helium. You will hold your breath for 10 seconds, then rapidly blow it out (exhale). The exhaled gas is tested to determine how much of the tracer gas was absorbed during the breath.

Lung imaging

If you enter the study after the first group of participants have already been enrolled and if you have a diagnosis of interstitial lung disease, you may be given the option to have high resolution computed tomography (HRCT) images taken of your lungs to help further understand the effects of the study treatment on the lungs. HRCT is a type of imaging that uses X-rays to create detailed images of the inside of the body. This will be an optional assessment. Up to 25 participants will be selected from the YTB323 arm and up to 10 from the comparator arm. Details of possible risks should be discussed with your study staff and/or the imaging facility (see Section ‘Risk associated with procedures’).

If you are given the option to undergo HRCT imaging, you will have HRCT scans taken before randomization and at Week 52. These scans will be sent (coded, and without personal identification information) to a central imaging vendor for analysis and archival. Your coded medical images will be used primarily for analysis as described in the informed consent. Your coded medical images may also be used for the development and evaluation of new methods of analysis directly related to the area of research that the study covers.

Any decisions about treatment of interstitial lung disease or other conditions observed from HRCT will be made by your Study Doctor.

Are there any additional procedures that are not a part of my normal standard of-care?

There will be no additional procedures in the study other than those mentioned above.

What other activities may I have to do during the study?

Before you receive study treatment and/or through the study:

If you are eligible to join this study and if you receive treatment with YTB323, you must agree to use an appropriate contraception method. If you are in the comparator arm, your Study Doctor will discuss your contraception requirements based on what treatment you will receive. See Section ‘What do I need to know about birth control, pregnancy and breast feeding?’ for further details.

If you are a female who is able to become pregnant, you will be asked to do urine pregnancy tests at home in case the study visits are more than 1 month apart. Your Study Doctor will provide you with the pregnancy tests. In case of a positive result at home, you must immediately contact your Study Doctor.

If you received YTB323 treatment

After you have received your YTB323 treatment, you will need to stay in the hospital for at least 2 weeks. Once you are discharged from the hospital, you will continue to be monitored closely for your safety and you will be instructed to remain near the study site (i.e., within 2 hours of total travel time) until at least 4 weeks after YTB323 administration. Additionally, a caregiver, family relative, or friend should stay with you during this time to monitor your well-being and contact your Study Doctor in case of any changes in your condition.

Tell your Study Doctor immediately if you get any of the following or combination of the following side effects after you have been given YTB323. These may happen in the first 8 weeks after the administration, but could also develop later:

• High fever (body temperature greater than 38°C/100.4 F) and chills. These may be symptoms of a serious condition called cytokine release syndrome (CRS, see Section ‘Are there any side effects (risks) if I join this study?’ for more information). CRS may be a life-threatening or fatal condition if not immediately treated. Other symptoms of CRS are difficulty in breathing, nausea, vomiting, diarrhea, muscle pain, joint pain, very low blood pressure, headache, heart failure, respiratory failure, kidney failure and liver injury. These CRS symptoms usually occur within the first two weeks after YTB323 administration. Feeling warm, fever, chills or shivering, sore throat or mouth ulcers may be signs of an infection. Serious infections, including life-threatening or fatal infections, have been observed (see more details in Section ‘Are there any side effects (risks) if I join this study?’).
• Problems such as altered thinking or decreased consciousness, delirium, confusion, agitation, seizures, difficulty speaking and understanding speech, loss of balance. These may be symptoms of a condition called immune effector cell associated neurotoxicity syndrome (ICANS) (see more details in Section ‘Are there any side effects (risks) if I join this study?’)
• Excessive or prolonged bleeding or bruising (more details in Section ‘Are there any side effects (risks) if I join this study?’)

In some circumstances, your Study Doctors may request that you are admitted to the study site to check how the study treatment is working, to monitor your safety and provide treatment for potential side effects following YTB323 administration. You will need to return to your Study Doctor at regular time points (as described above) so that your condition can be monitored.

Ability to drive and use machines

During the 8 weeks after YTB323 administration you should not drive or operate heavy or potentially dangerous machinery due to the potential for neurological events, such as dizziness, decreased consciousness, or coordination issues.

Supervised exercise program or physical therapy

During the first 52 weeks of the study, you should not change any supervised exercise program or physical therapy.

Donation of Blood or Tissue

There is no data on how long YTB323 can stay in different parts of your body. Therefore, do not donate blood, organs, tissues, oocytes, sperm, or cells after you receive YTB323 infusion.

Will I have access to study treatment after the study ends?

You will only receive one dose of YTB323 in this study as this is a single dose treatment, no further treatment will be available after the study ends.

If you are randomized to the comparator arm, you might be eligible to receive treatment with YTB323 after 1 year, in a separate study, but before Year 4 visit if you are not experiencing enough control of your symptoms as determined by your Study Doctor. If you complete the study while on the comparator treatment, the Study Doctor will discuss further treatment options available outside of the study.

Autopsy Information

If you pass away while you are in the study or soon after, the study doctor may ask your legally authorized representative (the person allowed by law to make decisions for you after your death) for permission to collect medical records related to your death.

If an autopsy (an examination of the body after death) is required as part of this study, your legally authorized representative will be asked to sign a separate consent form for the autopsy. If an autopsy is performed, the autopsy report and/or a copy of the death certificate, if available, will be sent (without direct identifiers) to the Sponsor as part of the clinical study information.

Researchers would like to encourage all participants in this study to consider having an autopsy, whether death occurs during the study or many years later. The purpose is to learn as much as possible about myositis, the effects of YTB323 or comparator treatment, and any long-term changes in the body. You cannot legally give permission for your own autopsy, this decision must be made by your legally authorized representative. The decision can be very difficult for families because it often comes at a very emotional time. Knowing your wishes ahead of time can make this easier for them. Please think about whether you would want your family to give permission for an autopsy and talk with them about your wishes, so they can make a decision that reflects what you would have wanted.

What are my responsibilities if I take part in this research?

If you choose to take part in this research, it is important to follow all instructions from the study doctor and study staff. This helps protect your safety and ensures that the information collected during the study is accurate.

If you join this study, you are responsible for the following:

• Follow the directions of the study doctor and research staff throughout the study.
• Tell your other health care providers that you are taking part in a research study so they can coordinate your care safely.
• Tell your study doctor about all medications you are currently taking or plan to take.
  This includes:
• Prescription medications
• Over-the-counter medicines (like pain relievers or allergy pills)
• Vitamins
• Herbal products or supplements
• Natural/alternative therapies
• Physical therapy or other non-drug treatments

Some medications or therapies may need to be stopped or changed for your safety or because they may interfere with the study treatment. Your study doctor will discuss this with you.

• Tell your study doctor right away if you think your myositis symptoms are getting worse.
  You may need “rescue treatment,” which your doctor will discuss with you if needed.
• Follow washout instructions (if required) for your current myositis medications before leukapheresis and before receiving YTB323. Some medications may need to be stopped or reduced for your T cells to be safely collected and for YTB323 to work properly.
• Avoid sharing information with the Blinded Assessor(s) about which treatment you are receiving.
  This includes:
• Whether you had leukapheresis
• Whether you had chemotherapy (lymphodepletion)
• Details about your hospital stay
• Your steroid dose
• Your opinions about your treatment

This is important so the study results are not biased.

Your study doctor will explain any other instructions that may apply to you throughout the study.

What happens if I say yes, but I change my mind later?

You may choose to leave the study at any time, for any reason, and without any penalty or loss of benefits to which you are otherwise entitled.

If you decide you no longer want to be in the study, talk with your study doctor about the safest way to stop.

Depending on where you are in the study, the doctor may request that you:

• Come in for a final study visit
• Complete certain tests (such as blood draws, urine tests, physical exam, or heart tests)
• Participate in follow-up phone calls for safety reasons

These steps help the study doctor make sure you stop the study treatment safely.

Even if you withdraw from the study, any information or samples already collected will remain in the study database and cannot be removed. This is necessary to maintain the scientific integrity of the research, unless prohibited by local law.

If you stop taking part in the study, the study team may ask for your permission to:

• Contact you in the future to check on your health
• Collect information from your regular medical care
• Continue monitoring for any delayed or long-term side effects (especially if you received YTB323)

You may say yes or no to these requests.

Can I be removed from the research without my OK?

This study and/or your participation in it may be changed or stopped at any time without your consent by the study doctor, Sponsor Pharmaceuticals Corporation, the U.S. Office for Human Research Protections (OHRP), or the IRB of Regulatory Institution. Your participation in this study may be stopped early if you cannot follow instructions, the doctor thinks it is no longer in your best interest to be in this study, or if you become pregnant.

If you are removed from the study or if your treatment is stopped early, your study doctor will explain whether you should continue study visits or complete a final visit with certain tests (for example, blood tests, urine tests, physical exam, vital signs, heart tests, neurological exam, or questionnaires).

If you received YTB323 at any point, you will be followed for 15 years after your infusion, whether you continue study visits or not, because YTB323 is a gene therapy product.

You will be told about any new information learned during your participation in this research if the information could relate to your willingness to continue to participate in this study. You may be asked to sign another informed consent and authorization form stating your willingness to continue participating in the study.

What are the risks of being in this study? (Detailed Risks)

While you are in this study, you are at risk for side effects. Some side effects may be mild, and some may be serious or life-threatening. Many side effects go away after treatment is stopped, but in some cases side effects may be long-lasting or permanent, and may even result in hospitalization or death.

Side effects will vary from person to person. Some side effects may occur after you have stopped receiving treatment. Tell the study staff about any side effects you may have, even if you do not think they are related to the study drugs or procedures.

Because this study uses several treatments together (YTB323, chemotherapy, pre-medications, and possibly other medicines), using these drugs together may cause side effects that are not seen when each is given alone, or may increase how often or how severe some side effects are.

Risks related to YTB323 and other CAR-T cell therapies

The YTB323 treatment, including its components and or procedures prior to YTB323 administration, can cause side effects, some of which may be serious or life-threatening, although not everyone gets them. Not all of the possible side effects of the YTB323 treatment are known at this time.

It is very important that you tell your Study Doctor if you have any complaints, side effects, or had other doctor visits or hospitalizations outside of the study.
YTB323 is an investigational treatment that has been given to a limited number of participants with malignant blood disease and lupus.

This research may involve risks that are currently unforeseeable, so tell your Study Doctor if you are experiencing any problems, even if you believe it is not due to study treatment. If you see a doctor other than your Study Doctor, please let him/her know that you are involved in a research study. You will be informed of any new information that may affect your willingness to start or continue in the study.

Identified side effects with the use of YTB323 and with similar CAR-T cell therapies
The below list of side effects contains side effects that have been identified with the use of YTB323 and with similar CAR-T cell therapies in participants with malignant blood disease. It is very important that you or your caregiver contact your Study Doctor immediately at any signs of fever or other new symptoms. Data from myositis participants are not yet available. In addition, problems or side effects not currently known could also occur.

To ensure that your Study Doctor can diagnose and treat any side effects as early as possible, you should stay within 2 hours of total travel time to your study center for at least 4 weeks after you receive the treatment with YTB323. During this period, it is very important that you take your temperature twice a day. Delayed side effects may occur. It is very important that you or your caregiver contact your Study Doctor immediately at any signs of fever or other new symptoms.

Cytokine release syndrome (CRS) and other systemic inflammatory conditions

Cytokine release syndrome (CRS) is a result of systemic inflammatory response caused by cytokines. Cytokines are signaling molecules which are naturally found in our body, helping with communication between different cells. Cytokines are usually released during an immune response, e.g., in case of an infection. CRS can vary in severity from mild to life-threatening, and fatal cases have been reported for cancer participants with malignant blood disease. In most cases, development of CRS occurs within the first 2 weeks after CAR-T administration. During this time, you will stay in the hospital so you can be closely monitored, but it may also happen after you leave the hospital. CRS symptoms can be progressive, it starts with fever and may end with organ failure. The most common symptoms are fever, nausea, vomiting, headache, skin rash, rapid heartbeat, and low blood pressure. Therefore, you should immediately contact your Study Doctor if you experience any of these symptoms. CRS can also lead to trouble breathing, heart failure, respiratory failure, and kidney and liver failure. Your Study Doctor is trained to monitor you closely and treat CRS (see also below tocilizumab). Symptoms of CRS typically resolve within 7 days.

Another hyperinflammatory condition that causes a systemic inflammatory response after CAR-T cell treatment is called Immune Effector Cell-associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS). It has only recently been identified and is still not very well-understood. Doctors are studying how to best diagnose and treat it. It occurs later than CRS, usually when CRS is getting better or has resolved. This condition can also vary in severity from mild to life-threatening and can even be fatal. It can increase the risk of serious infections and bleedings, and could also cause damage to the liver, spleen, lungs, heart, brain, and kidneys. Some of the symptoms are similar to those of CRS and may start after you have been discharged from the hospital. Therefore, it is very important that you immediately contact your Study Doctor if you experience any of these symptoms.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) is a neurologic syndrome. It is the second most common side effect that may develop in participants treated with CAR-T cells. ICANS has a diverse set of symptoms. It often starts with participants developing inattention, disorientation, difficulty speaking and understanding speech. Symptoms can be rapidly progressive so you will need to be closely monitored. In the most severe cases, participants may develop progressive lethargy, severe aphasia (difficulty speaking), seizures, or coma, and may require intubation and mechanical ventilation to support breathing. Your Study Doctor is trained about therapeutic strategies to manage ICANS. ICANS may occur up to one month after CAR-T administration. ICANS is often self-limited but can present with potentially severe symptoms lasting between 5 to 17 days.

Infections

Participants treated with YTB323 are at risk of infections. Infections as observed following YTB323 administration usually occur within 30 days and could be life-threatening. However, the infection risk may continue as long as the CAR-T cells are functional. These infections may require treatment with antimicrobials.

Some infections can be prevented with vaccines. If a vaccine is available for an infection that could affect you, your Study Doctor will recommend that you receive it. Your doctor will talk to you about which vaccines are right for you. Some infections can be prevented with vaccines. If a vaccine is available for an infection that could affect you, your Study Doctor will recommend that you receive it. Your Doctor will talk to you about which vaccines are right for you. YTB323 may also decrease the effectiveness of vaccines given after treatment but they can still provide a level of protection.

Prolonged depletion of B cells

B cells are expected to be eliminated by the YTB323 treatment for a period of time, which should be observed in all participants who respond to the treatment. Loss of B cells can result in participants being more susceptible to infections. YTB323 may potentially stay in the body for a very long period leading to prolonged depletion of B cells. The average time to B cell recovery was approximately 1 year after dosing for a similar CAR-T product in participants with malignant blood disease. Treatment with intravenous immunoglobin (human antibodies given through a vein) may be recommended to help protect against infections until your B cells recover.

Hematological disorders

YTB323 and/or lymphodepletion can lower one or more types of blood cells (red blood cells, white blood cells, or platelets) and the low blood cell counts may persist for several weeks after YTB323 treatment. Your Study Doctor will closely monitor and treat you as needed. You should contact your Study Doctor immediately if you get a fever, are feeling tired, weak, or short of breath, or have bruising or bleeding.

Other side effects

• Pale skin, weakness, breathlessness due to low number of red blood cells or low hemoglobin.
• Excessive or prolonged bleeding or bruising due to low number of platelets.
• Fever with dangerously low white blood cell count.
• Increased risk of infection due to abnormally low number of white blood cells
• Decrease in all blood counts.
• Fever, malaise, enlarged liver, yellow color of your skin and eyes, low blood cell counts due to severe immune activation.
• Frequent and persistent infections due to decreased antibodies in your blood.
• Abnormal blood test results (high or low levels of potassium, fibrin, D-dimer; low levels of phosphorus, calcium and magnesium; high levels of glucose, liver enzymes and bilirubin, low level of blood protein called albumin, sodium).
• High levels of liver enzymes, or creatinine in the blood that show that your liver or kidneys are not working normally. In severe cases, defective blood clotting, jaundice, ascites and confusion may be present.
• Low blood pressure.
• Nausea and diarrhea.
• Liver injury presenting with increased liver enzymes (aminotransferases and/or alkaline phosphatase and in moderate to severe cases total bilirubin).

Potential side effects of YTB323 treatment (delayed / gene-therapy-related)

Generation of Replication Competent Lentivirus
To manufacture YTB32, a lentiviral vector is used as a carrier to transfer genetic material to the T cells taken from your body. The lentiviral vector is made up of parts of the human immunodeficiency virus (HIV). The lentiviral vector does not behave like HIV and is not expected to cause HIV infection. However, there is a small chance that a small amount or parts of the vector may remain with the YTB323 product and could make you sicker than you are now. To date, no participant after YTB323 administration or any other type of CAR-T cell therapy has developed a replication competent lentivirus, but as per guidance for gene therapy medicinal products, participants exposed to YTB323 will be monitored for 15 years following administration.

Interference with HIV testing
There is a possibility that a small amount of parts of the lentiviral vector may remain with the CAR-T cells. This may cause the body to generate antibodies against HIV proteins. Therefore, you may test positive on some types of HIV tests. This means that after you get YTB323, some of the routine HIV tests may say you have HIV infection, even if you are not actually infected.

Malignancies (development of a cancer)
The study involves the administration of the participant’s own T cells after they have been modified using a lentiviral vector in order to manufacture YTB323. The lentiviral vector is not infectious and it usually does not cause any disease. There is a chance that the CAR-T cell manufacturing process may affect other genes in the T cells. In most cases, this effect will have no health consequences. However, there is a chance that this would increase your risk of getting cancers, including certain types of cancers of the immune system.

It is important that you know that this occurred in another gene transfer research study using a different type of retroviral vector. In this study, a newer lentiviral vector is used to safeguard against this risk.

If you develop a cancer, you will be asked to provide blood samples along with a portion of a biopsy of your tumor or other tissues (if applicable) for analysis. This is to evaluate if YTB323 is involved in the development of this cancer.

The Sponsor may be required to supply the data to organizations including but not limited to the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA), or country-specific gene therapy review committees.

In case of potential cancers, analyses of tissue samples may provide vital information about the long-term safety of the gene transfer therapy of the CAR-T production. Tissue samples will be used for conducting further analyses that may include but are not limited to understanding if YTB323 integrates into other genes in the body.

Your Study Doctor will monitor you for this during this study and for a total period of 15 years after YTB323 infusion if you agree to participate in the long-term safety follow-up after this study. The risk can remain for a long time after your participation in these studies has finished; therefore, your Personal Doctor should keep monitoring you for the risk of cancers. If you are diagnosed with cancer, your Personal Doctor should contact Sponsor and you will be requested to have blood and tissues collected and sent for testing.

Hypersensitivity including acute infusion reactions

Hypersensitivity reactions may happen right away (immediate) or several days after (delayed) after receiving your YTB323 infusion. Most hypersensitivity reactions are mild or moderate and usually stop with treatment. However, they can be severe or life-threatening. You will get other medicines, such as acetaminophen/paracetamol and diphenhydramine, before you receive YTB323 to lower the chance of these side effects.

There is a chance that some of the small particles used to make CAR T-cell therapy will not be completely washed away during the process. It is possible that the left-over particles could cause an allergic reaction. Please tell your study doctor if you have had a severe reaction to other medicines made with proteins or iron dextran in the past.

Hypersensitivity reactions include:
• Fever
• Chills
• Nausea
• Itchy skin
• Swollen skin
• Sneezing, and stuffy or running nose
• Swollen eye (“pink eye” or conjunctivitis)
• Trouble breathing
• Wheezing or coughing
• Fast heartrate
• Low blood pressure
• Severe allergic reaction (anaphylaxis or anaphylactic shock)

Risks associated with other medications used in this study

Lymphodepleting therapy (fludarabine and cyclophosphamide)

Before your YTB323 administration, you will receive lymphodepleting therapy with fludarabine and cyclophosphamide given intravenously (via a needle inserted into your vein). Common side effects of lymphodepleting therapy include nausea and vomiting. These symptoms can usually be controlled with anti-nausea medications. Hair loss can occur, but hair will usually grow back after the medication is stopped. Other common side effects include fevers, itching or skin rashes, loss of appetite, diarrhea, headache, muscle pain, weakness, dizziness, bruising, mouth sores, low blood cell counts, and increased risk of developing infections. These infections may require treatment with antimicrobials and possibly hospitalization. More rare side effects may include infertility, irritation of the bladder, increased risks of developing some types of cancers, vision problems, and neurological effects such as confusion, agitation and seizures.

Some of the side effects of lymphodepleting therapy may be serious. You should contact your Study Doctor if you notice the following: blood in the urine, fevers and chills, easy bruising or bleeding, shortness of breath or swelling of the face, lips, tongue, throat, feet and/or ankles. All risks will be fully explained by your Study Doctor, and your Study Doctor will also clarify any concerns or questions.
Full safety information about fludarabine and cyclophosphamide is available with your Study Doctor.

The following is a summary of the most common side effects other than those previously described, specific for each drug.

Fludarabine
Most of the safety information about fludarabine comes from patients treated for blood cancers. Fludarabine can cause a severe decrease in blood cell counts, which can lead to serious and sometimes fatal infections including pneumonia. Life-threatening and sometimes fatal reactions due to the attack of your immune system against your red blood cells or platelets (autoimmune reactions) have been documented. The use of fludarabine may also affect the nervous system, causing weakness, agitation, confusion, seizures, visual disturbances, blindness, and coma. Fludarabine has been shown to cause lung symptoms such as shortness of breath, cough, and loss of lung function. Excess fluid in arms and legs, blood in the urine, skin rashes and new skin cancers have also been reported.

Cyclophosphamide
Most of the safety information about cyclophosphamide comes from patients treated for cancers and severe autoimmune diseases. Cyclophosphamide can cause severe decrease in blood cell counts and severe suppression of your immune system which may lead to serious and sometimes fatal infections. Bleeding of the urinary bladder (sudden onset of blood in the urine combined with bladder pain and irritative bladder symptoms), urinary tract infections, bladder ulcerations, bladder fibrosis can occur and can lead to death. Cyclophosphamide can cause cardiotoxicity and lung toxicity which can lead to death. It can also cause the onset of tumors and affect fertility in women and men.
Cyclophosphamide is also sometimes used to treat myositis.

Pre-medication (paracetamol/acetaminophen and diphenhydramine)

Paracetamol/acetaminophen and diphenhydramine will be given before you receive treatment with YTB323. Side effects from paracetamol at the dose to be administered are rare but, can be mild to moderate and include nausea, vomiting, liver enzyme elevations, or low blood cell counts.
Side effects from diphenhydramine at the dose to be administered are expected to be mild and may include drowsiness and occasionally gastrointestinal disturbances, dryness of the mouth, vertigo, excitation, and headaches.

Tocilizumab (for cytokine release syndrome, CRS)

You may need to receive tocilizumab, also known as Actemra or RoActemra, if you develop CRS (see above). Tocilizumab can potentially reverse some of the symptoms associated with CRS when given intravenously (via a needle inserted into your vein). This medication has been used for treating CRS in pediatric and adult participants who have received tisagenlecleucel, a type of CAR-T cell therapy similar to YTB323. Tocilizumab has been approved in many countries for the treatment of CRS, including the United States, European Union, Australia and Japan.

Tocilizumab is mainly used in chronic indications such as rheumatoid arthritis and safety data related to its use for CRS are still limited.
Possible side effects associated with tocilizumab are listed below.

Most common adverse reactions (greater than 5% occurrence) include:

• Upper respiratory infections
• Nasopharyngitis (inflammation of the nose and throat)
• Headache
• Hypertension
• Increased liver test
• Infusion site reactions

Some of the serious side effects related to tocilizumab include:
• Serious infections
• Gastrointestinal (bowel) perforations
• Laboratory abnormalities (abnormal lipid and changes in blood neutrophil and
platelet counts)
• Increased liver enzymes and liver injury. In very rare cases, liver injury has
progressed to liver failure requiring liver transplantation.
• Allergic reaction

Tell your study doctor immediately, if you notice any of the following side effects after you have been given tocilizumab:
• Chest tightness
• Wheezing or difficulty breathing
• Severe dizziness or lightheadedness
• Swelling of the face, lips, tongue, throat or other parts of your body
• Rash, itching or hives on the skin
• Signs of serious infections such as fever and chills
• Stomachache or persistent headaches
• Bleeding from the stomach and intestines – signs and symptoms may include
stomach pain, vomiting blood or material that looks like coffee grounds, bleeding
from the rectum, black sticky feces, bloody diarrhea, severe blisters and bleeding in
the lips, eyes, mouth, nose and genitals
• Feeling tired, weakness, lack of appetite for several days or longer, nausea and
vomiting, yellowing of your skin or the whites of your eyes, confusion, abdominal
swelling and pain of the right side of your stomach area, dark ‘tea-colored’ urine,
light colored stools

Comparator arm treatments

Comparator arm treatments
Your Study Doctor will explain common side effects of the comparator treatment that you will be using during the study.

Risks associated with study procedures

Washout of your myositis medication

Washout of your myositis medication
Before your scheduled leukapheresis and again before lymphodepletion, you may be required to wash out (stop or decrease the doses of) your current myositis medication, including steroids. The duration of the washout periods can be between 3 days to at least 1 week, depending on which medication you are taking.

During the two washout periods of your myositis medication there is a risk that your myositis may get worse. If you develop any new or worsening symptoms, you should report this to your Study Doctor immediately. This potential disease worsening may be severe and/or result in temporary or permanent damage to your organ(s) and may require significant treatments or interventions.

In very severe cases there is a risk that the function of your organ(s) and/or your clinical condition may become no longer suitable for you to safely be treated with lymphodepletion or YTB323. You may have to wait some time until it recovers, or in more extreme cases it can make you no longer eligible to be treated with YTB323. Your Study Doctor can discuss these potential risks and options to prevent or treat myositis worsening, based upon your current disease condition.

Blood collection risks

As part of this study, you will have samples of your blood collected. The possible risks of collecting blood may include fainting, pain, and/or bruising, dizziness, and in rare cases, infection. Rarely, there may be a small blood clot or infection at the site of the needle puncture or central line.

Other risks of collecting blood may include tingling in lips or extremities, lightheadedness, dizziness, pale appearance, feeling cold or warm, chills, shortness of breath, hyperventilation, loss of bladder and/or bowel control, nausea and vomiting, generalized hives, itching, and/or rash, changes in blood pressure, tongue, throat, eyes, and/or face swelling, muscle cramps in your arm and legs, mental alteration; tremor, shock, or fever. Very rarely, heart failure, fainting or central nervous system events may occur.

You may also develop local leukapheresis catheter insertion site reaction such as itching, redness, rash, pain, swelling, pressure, tenderness, warmth, shooting pain down arm, weakness of arm, bruising, bleeding, and infection.

Biopsy risks

Biopsy risks
Ask the study staff to explain the biopsy procedure and its risks. You may also ask the Study Doctor any questions that you have.

Leukapheresis risks

Leukapheresis risks
Possible side effects of the leukapheresis procedure may include:
• Rapid pulse, slow pulse
• Numbness or tingling of fingers, hand, arm, lips
• Lightheadedness, dizziness, fatigue, paleness
• Cold extremities, chills, feeling warmth
• Shortness of breath, chest pain, hyperventilation
• Loss of bladder and/or bowel control
• Nausea, vomiting
• Sweating, twitching, weakness, anxiousness, restlessness
• Generalized hives, generalized itching, generalized rash
• High blood pressure, low blood pressure
• Scratchy feeling in throat, sneezing and nasal congestion
• Tongue/throat/eyes/face swelling
• Muscle cramps in your arm and legs, mental alteration, tremor, shock, fever
• Very rarely, cardiac insufficiency, fainting or central nervous system events may
occur
• Local leukapheresis catheter insertion site reaction: itching, redness, rash, pain,
swelling, pressure, tenderness, warmth, shooting pain down arm, weakness of arm,
bruising, bleeding, infection.

Imaging risks

Imaging risks
Ask the study staff to explain the imaging procedures you will have (ECHO and HRCT if applicable) and their risks in detail. You may also ask the local imaging facility any questions that you may have.

Other risks

Although every effort will be made to keep your study data and personal health information safe, there is a small chance that your information could be lost, stolen, or seen by someone who is not authorized to see it. This could result in a loss of confidentiality.

In addition to the risks described above, this research may hurt you in ways that are unknown at this time. These may be minor or may be so severe as to cause disability or death. You will be told about any new information that may affect your willingness to continue in the study.

Does this study involve genetic or genomic research?

Yes. This study involves gene therapy: your own T cells are genetically modified using a lentiviral vector to create YTB323. As described under “Generation of Replication Competent Lentivirus,” “Interference with HIV testing,” and “Malignancies (development of a cancer),” there are special long-term safety risks related to this genetic modification, and you will be monitored for 15 years after YTB323 infusion if you receive this therapy. Researchers want to learn if there is a relationship between a person’s genetic information (such as their genes or DNA) and their likelihood of getting the disease. They also want to understand whether genetic information affects how people respond to certain types of treatment.

Important: The main study does not include whole genome sequencing of your DNA. Researchers are not reading your entire genetic code. Instead, they are monitoring how the gene-modified cells behave in your body and whether they cause problems such as infections, changes in blood cells, or development of cancers.

However, there are optional parts of this study that may require whole genome sequencing, if you agree, to take part in optional genetic research.

Researchers will not share the results of any genetic testing performed as part of the main study. If you have questions about the genetic aspects of this therapy or about the effects on HIV testing or cancer risks, you should ask your study doctor or a genetic counselor.

Pregnancy Risks and Birth Control

Taking part in this study can pose unknown risks to an unborn or breastfeeding baby, so you must not become pregnant, father a child, or breastfeed while on this study.

If you are pregnant, trying to become pregnant, or breastfeeding, you cannot be in this study.

In addition, cyclophosphamide (one of the drugs used for lymphodepletion in the YTB323 arm, and also one of the possible comparator treatments) can affect fertility in both females and males. Your study doctor will talk with you about possible options to preserve fertility (for example, storing eggs or sperm) and the possible risks and outcomes.

Because of the unknown risks of YTB323 and the other study treatments, it is very important that you and/or your partner do not become pregnant while you are in this study.

You should discuss an effective way to avoid pregnancy that fits with your beliefs and values with your study doctor and/or your regular doctor.

If you receive YTB323

Females

• If you are a female who is able to become pregnant, you:
• Must use an effective method of birth control starting after you enroll in the study.
• Must continue birth control for at least 2 years after you receive YTB323, and
  keep using birth control until YTB323 (CAR-T) cells are no longer found in your blood on two tests in a row.
• The length of time that YTB323 cells remain in the blood can vary:
• In people with blood cancers, CAR-T cells may last from about 1 month up to more than 10 years, with an average of about 1 year.
• It is not yet known how long they stay in the blood of people with autoimmune diseases such as myositis.
• Your study doctor will:
• Review which birth control methods are acceptable for you during the study and during the required time after YTB323.
• Talk with you about what this means if you or your partner want to become pregnant in the future.
• After the study, your regular doctor can refer you for pre-pregnancy counseling (preconception advice) if you wish.
• You will have a pregnancy test before receiving study treatment and may have additional pregnancy tests during the study.
• If you are pregnant at screening, you will not be enrolled.
• If you become pregnant at any time, you must tell your study doctor right away.
• If you become pregnant before receiving YTB323:
• All study assessments and procedures will be stopped, and you will not receive YTB323.
• You will be asked to sign a separate consent form so your study doctor may ask you questions about your pregnancy and its outcome.

Do not donate eggs (ova) while you are in this study and for at least 2 years after YTB323 and until YTB323 cells are no longer found in your blood by two consecutive tests.

Acceptable birth control methods include:

• Hormonal methods (such as birth control pills, injections, or implants)
• Intrauterine device (IUD) or intrauterine system (IUS)
• Condom or occlusive cap with spermicide
• Surgical sterilization, such as tubal ligation (having your “tubes tied”), a hysterectomy (removal of the uterus), or surgical removal of the ovaries

Males

• If you are a male, you must:
• Use a condom during intercourse starting from enrollment into this study and
  continue for at least 12 months after YTB323 administration and
  until CAR-T cells are no longer found in your blood on two tests in a row.
• This condom requirement applies:
• Even if you have had a vasectomy,
• Even if your partner cannot become pregnant, or
• Even if your partner is male.
• A condom is required to prevent passing YTB323 to your partner through semen.
• You must not try to conceive a child (father a pregnancy) during the study and until you have had two negative tests showing that CAR-T cells are no longer present in your blood.
• Do not donate sperm after receiving YTB323.
• If your partner becomes pregnant:
• You must tell your study doctor right away.
• Your partner will be given a Partner Information sheet and may be asked to sign a separate consent form to allow the study doctor to collect information about the pregnancy and the baby’s health.

Because of the unknown risks of YTB323, it is very important that you (or your partner) do not become pregnant while you are in this study.

You should discuss an effective, acceptable method of birth control that is consistent with your own beliefs and values with your study doctor and/or your regular doctor.

If you receive a comparator treatment instead of YTB323

If you are assigned to the comparator arm and do not receive YTB323:

• Your contraception requirements (what kind of birth control you need to use and for how long) will depend on which comparator drug you are taking (for example, rituximab, cyclophosphamide, MMF/MPA, or tacrolimus).
• Your study doctor will explain:
• What birth control method(s) you should use, and
• How long you need to continue using them.

Because of the unknown risks of these study medications, it is important that you do not become pregnant during this study, whether you receive YTB323 or a comparator treatment.

You should discuss an effective way to avoid pregnancy that is in keeping with your beliefs and values with the study doctor and/or your own doctor.

Are there any optional parts of this study?

You are being asked to take part in some optional procedures related to this study.
You do not have to agree to any optional procedures to be in the main study.

Your decision to say “yes” or “no” to any optional part will not affect your ability to participate in the main study or the care you receive.

You can choose to be in some, all, or none of the optional procedures.
There is no cost to you for taking part in the optional procedures.
There is no direct benefit to you from the optional procedures, but future patients may benefit from what is learned.

Please initial or check your choice of “yes” or “no” for each of the optional parts below.

1. Optional Genetic Research

If you agree, you may take part in optional genetic research using a blood sample collected during the CYTB323L12201 main study.

What is genetic research?
Genetics is the study of genes, which are made of DNA and are inherited from your parents. Genes provide instructions for how your body grows, develops, and functions.
By taking part in this optional genetic research, you give permission for researchers to study your genetic data. This may include:

• Your entire genetic data (your genome),
• Many genes, or
• A single gene.

Health and medical information collected during the main study (such as test results, medications, and/or medical images) may also be used as part of this genetic research.

The most appropriate technology available at the time of the research will be used to read and analyze your genetic data. Technology may change over time, and your genetic data may be analyzed in the future using newer methods.

Purpose of the genetic research
The purpose of this genetic research is mainly to:

• Better understand the safety and how well YTB323 works,
• Learn more about myositis or other autoimmune diseases, and
• Help develop ways to detect, monitor, and treat diseases.

This genetic research is paid for by Sponsor (the Sponsor). Sponsor will use your genetic data only for genetic research on myositis and other autoimmune diseases.

What happens if I join this genetic research?

• During the main study, your study doctor or staff will take a blood sample of about 3 mL (just over half a teaspoon).
• This sample will be taken at Day 1 (randomization) or at a later visit.
• If the original sample is lost or damaged, you may be asked if you are willing to give another sample.
• There are no extra study visits just for this optional genetic research.

You can stop your participation in this genetic research at any time without leaving the main study.

Are there any benefits to me if I join this genetic research?

Your participation may help researchers learn how differences in genes affect health and disease. However:

• The results of this genetic research are not expected to benefit you directly.
• This research will not change your medical care.
• It will not provide a clinical diagnosis or advice about your personal disease risks.
• There is no plan to give you or your study doctor any individual results from this genetic testing.

Are there any risks if I join this genetic research?

1. Blood draw risks
• Fainting
• Pain and/or bruising
• Dizziness
• Rarely, infection or a small blood clot at the needle or central line site
2. Privacy and genetic information risks
• Genetic data is unique to you, and in some situations it may be possible to identify someone from their genetic data.
• In this study, the risk that someone could link your genetic data back to you is very small.
• The Sponsor will take precautions to protect your genetic data and privacy, and will not share your information with others (including family members) except as described in the consent or as required by law.

Genetic Information Nondiscrimination Act (GINA)

• In the United States, there is a federal law called the Genetic Information Nondiscrimination Act (GINA).
• In general, this law makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information.
• GINA does not protect against discrimination by companies that sell life insurance, disability insurance, or long-term care insurance.
• The chance that your genetic information would be released to such companies is small.

As technologies and medical knowledge advance, future uses and future risks related to genetic data are not fully known today.

Your choice for Optional Genetic Research

___ Yes, I agree to take part in the optional genetic research as described above.

___ No, I do not agree to take part in the optional genetic research as described above.

2. Optional In-Trial Interviews (Patient Experience Interviews)

You may be asked to take part in optional in-trial interviews (also called patient experience interviews). These interviews help researchers understand your experience living with myositis and your experience with the study treatment.

What will happen if I join the interviews?

• There will be two interviews:
• The first interview will take place during the screening period (within 10 days before your randomization date).
• The second interview will take place within 10 days after your Week 52 visit.
• If you stop treatment before Week 52, you may still be eligible for a second interview after your early discontinuation.
• Each interview:
• Will be conducted by trained external staff acting on behalf of Sponsor.
• Will be done by phone or teleconference in your country’s language.
• Will last up to about 1 hour.
• Will be scheduled at a time that is convenient for you.

The interviews will focus on:

• Your experiences with myositis and how it affects your daily life, and
• Your experience with the study treatment and any changes you notice over time.

Who will see my information for the interviews?

• Sponsor will use an outside company to carry out the interviews.
• To arrange and conduct these interviews, this company will receive limited personal data that can identify you directly, including:
• Your study ID number
• Your first name
• Your phone number
• Your email address
• The dates of your Screening, Randomization/Baseline, and Week 52 visits
• This company:
• Will use this information only to schedule and conduct the interviews, ask any follow-up questions, and share study-related information with you or your study doctor as needed.
• Will not have access to other health information about you beyond what you share during the interview.

Will the interviews be recorded?

• The interviews will be audio-recorded and written down (transcribed) for analysis.
• The written transcripts will be anonymized (your identifying information will be removed).
• The anonymized transcripts may be combined with other study data and shared with:
• Sponsor (the Sponsor), and
• Regulatory authorities, if required.
• The audio recordings themselves will not be shared with Sponsor.

Taking part in these interviews is optional and will not affect your participation in the main study.

___ Yes, I agree to take part in the optional in-trial interviews as described above.

___ No, I do not agree to take part in the optional in-trial interviews as described above.

3. Optional Consent for Additional Research

If you agree, during or after the study, Sponsor may use your Coded Data (information with your personal identifiers removed) and/or leftover biological samples collected during the main study for Additional Research.

Purpose of Additional Research

• To learn more about human diseases related to your condition, and
• To help develop or improve ways to detect, test for, monitor, and treat those diseases.

The exact future research projects are not known now.
Sponsor may do this research alone or with other scientists or partner companies around the world, and may combine your Coded Data with data from other people to help advance science and public health.

What does this involve?

• Only leftover samples and data from the main study will be used.
• No extra study visits and no extra sample collections are required.

Privacy and ownership

• Your data will be “Coded”, meaning information that directly identifies you (like your name or date of birth) is removed and replaced with a code.
• Sponsor limits who can see Coded Data to protect your confidentiality.
• Coded Data cannot be used to contact you and cannot affect your care or other decisions about your life.
• You will not own any data or discoveries that result from this research;
  Sponsor will own that data.
• Coded Data used for Additional Research will not become part of your medical record.

If you change your mind

• You or your legal representative may withdraw this optional consent at any time by writing to your study doctor.
• After that, your Coded Data and samples will not be used for any new Additional Research.
• However, any research already done with your data or samples cannot be undone, and those prior results will be kept.

Your choice for Optional Additional Research

___ Yes, I authorize the use, access, and sharing of my Coded Data and samples for the purposes described above.

___ No, I do not authorize the use, access, or sharing of my Coded Data and samples for the purposes described above.

4. Optional Consent for Activities That May Be Done Outside of the Study Site (Off-Site Activities)

Sometimes, especially during a public health emergency (for example, when travel or clinic access is limited), some study activities may need to be done outside of the main study site, such as at your home or another suitable location.

This optional consent allows your study team to perform certain study-related activities off-site instead of only at the clinic.

What does this involve?

• Your study doctor will still be responsible for your care and will work closely with any health care professionals involved in off-site activities (for example, a visiting nurse or local clinic staff).
• Off-site activities may include (when needed during a public health emergency):
• Home visits by health care professionals (such as a nurse)
• Visits to another location (local hospital, clinic, or lab) where another doctor may see you instead of your study doctor
• Video calls or other remote communication with members of the study team
• Having certain study materials (such as your study treatment) shipped to your home or another agreed-upon place

The type and frequency of off-site activities will be similar to what would have been done at the study site but performed in an alternate location when necessary.

Your study doctor will tell you which visits are on-site and which are off-site, may change this plan if needed, or may stop off-site activities and ask you to return to on-site visits instead. You can also discuss with your study doctor if you want to stop off-site activities and switch back to on-site visits.

The above information is summarized for you in the table below:

The off-site visits will be performed at the same frequency and in the same way as at the on‑site location but may be replaced by the off-site activities in Table 1-1.

Table 1-1 Off-Site activities

Off-site activity	As part of your usual study participation	Due to a public health emergency
Off-site visits from health care professionals, such as a nurse.	No	Yes
Visiting another location, such as a local hospital/clinic/lab. If you visit a different location, another health care professional, such as a doctor, may see you instead of your Study Doctor.	No	Yes
Video calls or other communication with health care professionals who are working on the study.	No	Yes
Study materials such as your study treatment, may be sent to your home or other location.	No	Yes

Benefits

• Off-site activities may reduce travel time and burden during the study, especially in situations like a public health emergency.

Risks

• If you need urgent medical attention during an off-site visit and it cannot be provided where you are, you may need to:
• See your study doctor urgently, or
• Go to a local emergency room.
• In some cases, it may take longer to get emergency care from an off-site location than at the study site.

Your responsibilities and costs

• You must make sure any off-site location (home or other place such as work, school, hotel, or health care facility) is appropriate and permitted for study activities.
• If it is not your home, you may need to confirm you have permission to use that location for study assessments.
• There are no additional costs to you for off-site study activities.
• If you have allowable expenses related to off-site visits (such as parking or transportation), these may be reimbursed according to local rules.

What happens to my personal data for off-site activities?

• Your study doctor may need to share limited personal information (such as your address, phone number, or email) with health care professionals who help with off-site visits.
• The Sponsor (Sponsor) is not involved in these specific data transfers and does not receive your personal contact information for this purpose.

Your choice for Optional Off-Site Activities

___ Yes, I agree to take part in off-site activities as described above.

___ No, I do not agree to take part in off-site activities as described above.

5. Optional HRCT Lung Imaging for Selected Participants

If you join the study after the first group of participants is enrolled and you have a diagnosis of interstitial lung disease, you may be offered additional optional lung imaging using high resolution computed tomography (HRCT) scans.

• Up to 25 participants in the YTB323 arm and up to 10 participants in the comparator arm may be selected.
• If you agree and are selected, you will have HRCT scans:
• Before randomization,
• At Week 52, and
• At Week 260 or End of Study (EOS).

The purpose of these optional HRCT scans is to provide more detailed information about how your lungs may be affected over time.

Details about HRCT, including how it is done and possible risks (for example, radiation exposure), are described in the “Lung Imaging” section of this consent and in the “Risks associated with procedures” section. You should talk with the study staff and/or the imaging facility if you have any questions.

Your choice for Optional HRCT Assessment

___ Yes, I agree to take part in the optional HRCT assessment for selected participants as described above.

___ No, I do not agree to take part in the optional HRCT assessment for selected participants as described above.

6. Optional Consent for Use of Travel Assistance Services

As a participant in the CYTB323L12201 study, you may choose to use optional travel assistance services to help you attend study visits. This service:

• Is provided at no cost to you.
• Is optional and will not affect your ability to participate in the study if you choose not to use it.

Sponsor has hired a company called Greenphire to provide these services. Your study staff can answer questions about how travel and payments are arranged.

What does this include?

1. Patient Stipend
• You will receive a per-visit stipend after each required study visit.
• This stipend will be loaded onto a pre-paid debit card by Greenphire, usually within 24 hours of your visit.
2. Study-Related Travel and Expenses
• Reasonable study-related expenses (for example, transportation or parking, as allowed by policy) can be reimbursed onto the same debit card when you provide receipts, following the study’s reimbursement rules.
• For non-local travel, you or the study staff will request your travel through Greenphire’s Travel Vendor Portal.
• The cost of approved travel and accommodations will be paid directly by the study.

To arrange travel and provide itineraries, Greenphire and the travel vendor will need some personal information about you, such as:

• Name
• Address
• Date of birth
• Email address

Additional information may be needed by the travel vendor to complete bookings.

1. Text and Email Notifications
• You may choose to receive appointment reminders and payment alerts by text message and/or email.
• To send these, Greenphire will need your mobile phone number and/or email address.
• Standard text messaging rates may apply.

Privacy information

• Your information will be transferred or accessed in the United States so that Greenphire can provide these services.
• Legal agreements between Sponsor and Greenphire require that your personal information be protected during transfer and use.
• Greenphire uses administrative, physical, and technical safeguards to protect your information and will use your personal data only to provide the travel and payment services.
• Greenphire will not share your personal information with Sponsor, will not sell it, and will not use it for other purposes.
• Your information will be kept as long as needed to provide the services and comply with applicable laws.

You can ask to access, correct, modify, or delete your information at any time by contacting the medical staff for the CYTB323L12201 study. If you take away your consent, your information will no longer be sent to Greenphire, but this will not affect any processing that already took place.

Tax information

• Payments you receive for being in a research study (including stipends, gift cards, or other items of value) are considered taxable income under IRS rules.
• If the total amount you receive in a calendar year is $600 or more, you will be issued a Form 1099, and you will be asked to provide your Social Security Number.
• No taxes will be withheld from these payments. You are responsible for reporting this income on your tax returns and paying any taxes due.

Your choice for Optional Travel Assistance Services

___ Yes, I agree to take part in this Optional Reimbursement/Travel Assistance Program as described above.

___ No, I do not agree to take part in this Optional Reimbursement/Travel Assistance Program as described above.

What are the costs of being in the research?

You will not have to pay for any study treatment(s) or any study-related tests/procedures while you are in the study. However, the Sponsor will not pay for the costs of the usual care you need to maintain your health.

Standard medical care that you receive under this research study but that is not specific to the research will be billed to your health care plan and/or you in the ordinary manner. Before taking part in this study, you may ask about which parts of the research-related care may be provided without charge, which costs your health care plan may pay for, and which costs may be your responsibility.

In some cases, insurance will not pay for services ordinarily covered because these services were performed in a research study. You should check with your insurance to see what services will be covered by your insurance and what you will be responsible to pay. A member of the study team can talk to you about what procedures would be considered standard care and the coverage of those costs.

There are no costs to you for any study-related activities done offsite. However, if you have certain expenses related to the offsite visit (such as parking fees, transportation costs), you will be reimbursed for those charges, as appropriate and per local regulation.

You must ensure off-site locations that you choose to use are suitable, and if not your own home (e.g., place of employment, school, hotel, healthcare facility) that you have approval from the owners or representatives of the off-site location to have study assessments performed there. You may need to provide written confirmation that the off-site location is suitable to the people who are involved in the off-site activities.

Your Study Doctor will discuss the options for off-site activities and steps to facilitate these.

Will I be paid for being in this study?

Samples that are collected from you in this study are the property of Regulatory Institution and may be used for the development of treatments, devices, new drugs, or patentable procedures that may result in commercial profit. There are no plans to compensate (pay) you for any patents or discoveries that may result from your participation in this research.

A per visit stipend and travel assistance services are made available to you to help support your participation in the clinical trial. This service is provided at no cost to you, and it is an optional service. You can choose to use it or not and it will not affect your participation in the trial. Greenphire is a company working on behalf of Sponsor to support this process.

Compensation will be provided by Greenphire, Inc. To support this compensation process, Greenphire, Inc. will need to process certain personal information about you. This information will be collected from you by the study site and given to Greenphire, Inc. through the Greenphire, Inc. portal. The personal information you provide is stored in a secure, electronic database that has access limited to only those who need to know your information. Those parties include the study site, and Greenphire, Inc. and their service providers who host data or provide tax processing services. Greenphire, Inc. employs reasonable precautions to prevent your personal information from loss, misuse, unauthorized access, disclosure, alteration or destruction.

You will be issued a Greenphire, Inc. ClinCard, which is a debit card that your stipends are loaded onto and can be used at your discretion. When a visit is completed, funds will be approved and loaded onto your card. Once approved to be released to your card, the funds will be available for use within 1 business day. In order to assign a ClinCard to you and load funds onto the ClinCard, the study site will provide Greenphire, Inc. with your Name, Address, and Date of Birth.

You will receive payment for the time spent in the study. You will receive $104.00 per completed protocol required study visit.

If you receive $600 or more during a calendar year from the Regulatory Institution for participating in research, you will need to provide either your social security number or Individual Taxpayer Identification number (ITIN). If you do not have one of these, the study team will speak to you about your options regarding participation in the study. If you receive more than $600 in a calendar year for your participation in research, you may receive a 1099for tax reporting purposes and Regulatory Institution may report this to the IRS as income you have received.

You will find further information on this optional service at the end of this informed consent form. Your study team can assist you with any further questions.

What if I am hurt or injured during the study?

If you have a research-related injury, Regulatory Institution providers will provide medical care. A research-related injury is an illness directly caused by the study drug(s)/device or a study procedure. A research-related injury does not include:

• injuries directly caused by the natural worsening (progression) of an underlying disease or medical condition, or
• injuries caused by you not following the instructions in this consent form
• the Study doctor or research site failure to follow instructions or failure to provide appropriate care

If you have a research-related injury, the sponsor will pay for the reasonable costs of necessary medical treatment of the injury, but neither the sponsor nor Regulatory Institution will reimburse you for other expenses, such as lost wages, disability, or discomfort. However, by signing this form, you are not giving up any of your legal rights.

Tell the Study Doctor if you think that being a patient in this study has caused you to be harmed. The Study Doctor will tell you how you can get medical care for your problem and how to receive it. The Study Doctor’s contact information is listed in this document.

If you think you have a research-related injury or have questions about a research-related injury, you should contact the study doctor or call the Regulatory Institution IRB at 346-356-1400.

By signing this consent, you do not give up any legal rights.

What is Personal Data and Protected Health Information (PHI) and What Happens With It?

During this clinical study, the Study Staff will collect certain information/data about you called “Personal Data and PHI”. Personal Data or PHI includes all medical information collected or created as part of this study. Access to your Personal Data is needed for all purposes necessary to conduct and ensure the integrity and effectiveness of the study.

Authorization for Use and Disclosure of Protected Health Information (PHI):

During the course of this study, your PHI, including identifying information about you, will be collected from your medical record. Examples of information that may be collected from your medical record include, but is not limited to:

• Your name, full date of birth, sex, race/ethnicity
• Address and phone number
• Your medical history, including types of medications/vaccines you have received, and results of tests/procedures
• Information related to your participation in this research study (such as results from research-specific tests/procedures)
• Images (such as X-rays, scan results, photographs), videos, and other recordings of you that are taken as part of the study
• Genetic or genomic data learned by testing the tissue and blood samples you provided

Information about HIV infection, drug abuse, alcohol abuse, behavioral health, and psychiatric care will be collected for this study and submitted to the sponsor.

If you agree to take part in this study and sign this form, you are authorizing the use, collection, and disclosure of your health information for purposes related to this study.

Your doctor and the research team may share your PHI with:

• State and federal agencies that require reporting of clinical data (such as the FDA, Office of Human Research Protections [OHRP], and the State Health and Human Services Commission);
• Regulatory agencies from other countries;
• The IRB and employees and health care providers of Regulatory Institution, including the study team and study doctor;
• Sponsor who is a sponsor/supporter of this study, and/or any future sponsors/supporters of the study;
• Study monitors and auditors who verify (check) the accuracy of the information;
• Individuals who put all the study information together in report form;
• The Sponsor’s collaborators and partners (such as researchers who work with the Sponsor or commercial partners and staff at scientific journals)
• Vendors (people who work on the study for the Sponsor, such as a Contract Research Organization [CRO] or a home-nursing vendor; courier for home delivery of study treatment, or travel service through Greenphire’ s vendor
• The Study site may share Personal Data with clinical trial recruitment provider(s) with whom you may have engaged- for instance, a trial pre-screening website or a call center- to inform them of whether or not you were enrolled in the clinical study and to evaluate the effectiveness of the recruitment process
• Another company potentially buying the Sponsor or part of the Sponsor’s business,

Your PHI is being collected and used by the people listed above for legal, ethical, research, and safety-related reasons, such as:

• To perform the research that is described in this consent form
• To check that the study is being safely and correctly done
• To support clinical trials being done at Regulatory Institution
• To check the safety or effectiveness of the treatment being studied, improving designs of future studies, or to get approval from health authorities for the treatment in this study
• To allow health authorities to oversee and review this research study to decide if approval can be given to the treatment in this study

Regulatory Institution has strict rules in place to limit who has access to your name, address, phone number, and other information that can identify you. Some organizations may be required to inspect and/or copy your information during the monitoring process.

Your information may be shared electronically. Your electronic data will be treated with the same level of protection as your paper records under federal and State law.

Data collected from you during the study will be coded. This means any information that could link you to your data (such as your name or date of birth) will be removed and replaced with a code. The code can link you to your identity, but the link will be kept in a separate location from your study data. Only researchers at Regulatory Institution will have access to this link.

Not all of the parties who will have access to your Personal and/or Coded Data as part of the study are prohibited by federal law from further sharing it, so the Coded Data, once received by them, may no longer be protected by federal law. The people/organizations listed in the section above may be located in countries other than yours, but during the transfer of the Coded Data, the Sponsor will ensure the protection and privacy of these data, as required by law.

You have the right to review and correct certain Personal Data. However, during the study, access to the Personal Data may be limited to protect the integrity of the study. You may have access to your Personal Data at the end of the study.

The Sponsor keeps the Coded Data and may use it to support scientific research including sharing with external partners, such as other researchers, staff at scientific journals and commercial partners for research, publication and education purposes.

All study data will be stored in password-protected computers and/or locked file cabinets for a minimum of 6 years and will continue to be stored securely after the study. Only the study doctor and the study team will have access to study data.

If you are (or have been) a patient at Regulatory Institution, your electronic medical record may be linked to your participation in this study. This includes a copy of this informed consent form and information about your participation in this study (such as the type of study drug or device you are receiving). This information is added to your medical record to help your doctors best care for you. By adding this information to your medical record at Regulatory Institution, it may mean that other Regulatory Institution doctors, nurses, and authorized staff who are not part of the research team but who provide other medical care for you will know that you are in this research study. The information in your medical record will be treated with the same level of protection as described in this consent form and will be protected in accordance with all applicable laws.

The research team may use your information in your Regulatory Institution medical record to tell you about appointments, send appointment reminders, or schedule additional appointments with you.

Tell any other non-Regulatory Institution doctors or medical teams who care for you that you are in a research study. This is for your safety.

Some infectious diseases like HIV/AIDs, hepatitis, and sexually transmitted diseases (STDs), are reportable diseases in State. If you test positive for these diseases, the law requires your study doctor to report your name and other identifying information (such as your phone number and address) to the appropriate authority. Other than this required reporting, your information will be treated as confidential as possible to the extent allowed by law. Ask your study doctor for details if you have concerns about this report.

Signing this consent and authorization form is optional, but you cannot take part in this study if you do not agree and sign.

Regulatory Institution will keep your PHI confidential when possible, according to state and federal law. However, if PHI is shared outside of Regulatory Institution, federal privacy laws may no longer protect your PHI.

The permission to use your PHI will continue indefinitely (forever) unless you withdraw your authorization in writing. There is no set date at which your information will be destroyed or no longer used because the researchers will need to review the data for many years, and it is not possible to know when they will complete the review of all data.

If you withdraw your authorization, you will not be able to continue taking part in this study. The information collected from you before your withdrawal can still be used as described in this form.

If you withdraw this consent, then the Study Doctor and Staff will no longer use or disclose your Personal Data or PHI [and biological samples, if applicable], unless it is necessary to do so to preserve the scientific integrity of the study. The already-analyzed Personal Data/samples will still be used to ensure the data integrity of the study.

To withdraw your authorization, you may write to the study doctor or to the Human Subjects Research Office at Regulatory Institution Research Institute, 6670 Bertner Avenue, Medical, STATE 12345, or you may call 346-356-1400.

What happens to the results after the study?

Your Study Doctor will receive a summary of the overall study results written for the study participants after the study is completed and all data examined. You may reach out to the Study Doctor to share these results with you. You can also find a summary of the overall study results written for study participants at http://www.xfictrd.com

A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time. These websites will not include information that can identify you. You can search the websites at any time using the study code CYTB323L12201.

A summary of the study results may be published at conferences or in journals. If the results of the study are presented to the public, you will not be named. Some authorities may ask that the Sponsor disclose study data for transparency reasons. However, the data shared will not identify you.

Are there any other situations where my Personal Data or PHI may be shared?

In rare instances, a nurse, Study Doctor, or laboratory technician, may be exposed to your blood, tissue or body fluids by needle injury, cut, or damaged skin. If this happens, it may be necessary to test your sample for certain viral infections including Hepatitis B and C and HIV. If possible, this will be done on a sample already available. The result will be shared with the person who was exposed to your blood, tissue, or body fluids, making it possible for that person to receive proper monitoring and treatment, as needed. Your Study Doctor will inform you of this situation and the next steps in accordance with the study site’s policies.

By law, positive test results for such reportable diseases must be shared with public health authorities.

Personal data collected can also be accessed, used and stored by the Sponsor for the purpose of full traceability of cells and/or YTB323 product.

What happens to the information collected for the research?

Most tests done on samples in research studies are only for research and have no clear meaning for health care. If research tests done on your samples show that there may be some meaning for your health (and the samples and results can be linked back to you), the researchers will not contact you to let you know what they have found.

Efforts will be made to limit the use and disclosure (sharing) of your personal information, including research study records, to people who have a need to review this information. Complete privacy cannot be promised. Organizations that may inspect and copy your information include Regulatory Institution, Health Authorities (government groups such as the U.S. Food and Drug Administration ‘FDA’), Institutional Review Boards (‘IRBs’), Sponsor and any sponsor representatives

Will data or leftover samples be used for future research?

Your personal information and/or samples are being collected as part of this study. These data (including images, if images are taken) and/or samples may be used by researchers at Regulatory Institution and/or shared with other researchers, the government, or other institutions for use in future research.

Before being shared or used for future research, every effort will be made to remove your identifying information from any data and/or samples. If all identifying information is removed, you will not be asked for additional permission before future research is performed.

If any future research is performed outside of Regulatory Institution, Regulatory Institution will not have oversight of the data/samples.

Purpose of Additional Research:

• To learn more about human diseases related to your condition
• To help develop or improve ways to detect, test for, monitor, and treat those diseases

The exact future research projects are not known now. Sponsor may do this research alone or with other scientists or partner companies around the world and may combine your Coded Data with data from other people to help advance science and public health.

The Sponsor has asked for your permission to use your data and samples for future research. Please see the Optional Studies section of this document for more information.

Requests may come from any Health Authority to do more testing on your samples. Most of these requests are to ensure the safety of the study medication. The Sponsor will comply with these requests when possible, and, as with all your data, this information will remain confidential.

The Sponsor may keep biological samples for up to 15 years after the study ends and then destroy them. These samples will be kept in a secured environment and you cannot be identified. You can ask your Study Doctor to inform the Sponsor to destroy your unused biological samples at any time during or after the study.

PARTICIPANT’S CONSENT/AUTHORIZATION

Protocol title: A Phase 2, randomized, open-label, controlled study to evaluate the efficacy and safety of rapcabtagene autoleucel versus comparator in participants with severe refractory idiopathic inflammatory myopathies.

I have read this document/had its contents explained to me. I understand the purpose of this study and what will happen to me during the study. I freely give my consent to join this study, as described in this document. I understand that I can stop participating in this study at any time. I understand that I will receive a copy of this signed and dated document.

By signing this consent form, I authorize the use, access, and sharing of my Personal and Coded Data, including my biological samples (such as blood and tissue), as described in this document.

I am not giving up any of my legal rights by signing and dating this form.

This consent is valid unless and until I cancel it.

PARTICIPANT’S CONSENT/AUTHORIZATION

By signing this consent form, I am agreeing that:

• I have been given the chance to ask questions and my questions have been answered. If I have more questions, I have been told who to call.
• I have had a chance to think about taking part in this study and talk about it with others as needed.
• I agree to be in the research study described above.
• I will be given a copy of this consent / authorization form after I sign it.

________________________________________ _________

SIGNATURE OF PARTICIPANT DATE

_________________________________

PRINTED NAME OF PARTICIPANT

WITNESS TO CONSENT

I was present during the explanation of the research to be performed under this protocol.

_________________________________________________ _________

SIGNATURE OF WITNESS TO THE VERBAL CONSENT DATE

PRESENTATION (OTHER THAN PHYSICIAN OR STUDY CHAIR)

A witness signature is only required for non-English speakers utilizing the

short form consent process (VTPS) and patients who are illiterate.

_____________________________________________________

PRINTED NAME OF WITNESS TO THE VERBAL CONSENT

PERSON OBTAINING CONSENT

I have discussed this research study with the participant and/or his or her authorized representative, using language that is understandable and appropriate. I believe that I have fully informed this participant of the nature of this study and its possible benefits and risks and that the participant understood this explanation.

______________________________________________ _________

PERSON OBTAINING CONSENT DATE

______________________________________________

PRINTED NAME OF PERSON OBTAINING CONSENT

TRANSLATOR

I have translated the above informed consent as written (without additions or subtractions) into and assisted the people

(Name of Language)

obtaining and providing consent by translating all questions and responses during the consent process for this participant.

_____________________ _______________________________ ________

NAME OF TRANSLATOR SIGNATURE OF TRANSLATOR DATE

Please check here if the translator was a member of the research team. (If checked, a witness, other than the translator, must sign the witness line.)