Changing the possible for patients

What is Sana doing? What is cell therapy?

Cell therapy is the use of live cells in a patient to treat a disease.

Sana is working on a type of cell therapy that is sometimes called ex vivo cell therapy.

Cells are collected from either the patient or a healthy donor and are modified outside the body (ex vivo) to make them into a medicine.

If the cells are collected from the patient, it is called an autologous cell therapy. If they are collected from a healthy donor, it is called an allogeneic cell therapy. These modified cells are then transferred into a patient to treat a disease.

Examples of ex vivo cell therapies include the autologous CAR T cell therapies approved for the treatment of large B-cell lymphoma. Sana is studying an allogeneic cell therapy approach with the goal of making more consistent and accessible medicines.​

Chimeric Antigen Receptor (CAR) T Cell

• CAR T cell therapies are a new class of medicines derived from the white blood cells that normally circulate in the blood or tissues and are part of the immune system that typically protects the body from infections and foreign substances.
• The cells of the immune system that are used in these therapies are T cells.
• CAR T cell therapies use the patient’s own T cells (autologous) or healthy donor T cells (allogeneic) as the starting material to make the CAR T cell therapy.

• T cells are modified to make them CAR T cells. These modifications allow the CAR T cells to recognize a protein on the surface of disease-causing (pathogenic) cells and then attack and destroy the pathogenic cells.
• CAR T cell therapies can be designed to recognize and attack pathogenic cells associated with blood cancers and autoimmune diseases.

Several CAR T cell therapies have been approved by the Food and Drug Administration (FDA) for certain patients with lymphoma, leukemia, or multiple myeloma. CAR T cells are a new approach to treating cancer – using immune cells – but current therapies have limitations that may prevent this therapy from reaching its full potential. Sana’s research focuses on enabling areas where we believe there is the greatest opportunity to help patients using CAR T cell therapy.

Currently approved CAR T cell therapies use the patient’s own immune cells (autologous CAR T). The challenge with this approach is that every patient must wait for their T cells to be collected and then modified. This potentially results in:

• Limited patient access
• Treatment often at specialty cancer centers
• Patient burden to supply their own T cells (apheresis)
• Prolonged manufacturing time and occasional manufacturing failures
• Sub-optimal T cell quality, as the cancer or cancer treatments may have impacted the patient’s T cells

Many are developing allogeneic CAR T cell therapies (using healthy donor cells) to overcome these limitations. However, there are also challenges with this approach, which include:

• Allogeneic CAR T cells can react against and attack the patient’s healthy cells and tissues (known as graft-versus-host disease [GvHD])
• Allogeneic CAR T cells can be rapidly cleared by the patient’s immune system because they are foreign “non-self” cells, and this can limit the ability of these cells to persist and kill disease-causing cells (known as host-versus-graft reaction)​

Sana is developing hypoimmune allogeneic CAR T cell therapies to overcome the limitations of current approaches

Sana’s hypoimmune CAR T cells are designed to avoid GvHD, to avoid immune rejection by the patient, and to attack and destroy disease-causing cells. T cells are isolated from a healthy donor and modified using the following steps:

1. Delete proteins on the donor T cells that look foreign to the patient’s immune system
2. Increase another protein that signals to the patient’s immune system not to attack the CAR T cells
3. Add specialized receptors to the donor T cell that both recognize disease-causing cells and signal to the T cell to kill those cells
4. Delete a protein on the surface of the donor T cell that might otherwise signal to the donor T cell to attack healthy cells and tissues in the patient’s body​

Sana’s hypoimmune CAR T cell platform uses healthy T cells that may improve function with reduced risk of manufacturing failures and is ready for immediate use (no wait time), improving patient access and simplicity of care.

T cells from a healthy donor are modified to create hypoimmune CAR T cells with a goal of both avoiding rejection by the patient AND attacking and destroying disease-causing cells

Hypoimmune CAR T cells created from a healthy donor may be given to many patients for immediate use (“off-the-shelf”), improving patient access and simplicity of care

•  Express CD47 to prevent the study drug from being rejected by a part of the patient’s immune system (innate immune system)
•  Express a CAR to attack and kill disease-causing cells by targeting proteins that are found specifically on the disease-causing cells
•  Remove proteins to prevent the study drug from being rejected by another part of the patient’s immune system (adaptive immune system)
•  Remove proteins to prevent the study drug from attacking healthy cells and organs in the patient’s body

Abbreviations:

• Human Leukocyte Antigen class I (HLA I)
• Human Leukocyte Antigen class II (HLA II)
• T cell receptor alpha (TCRa)

Targeting B cells in autoimmune diseases and blood cancers

• B cells are white blood cells (lymphocytes) that normally help protect the body against bacteria or viruses by making proteins called antibodies. Antibodies attach to the bacteria or viruses, marking them for destruction by other parts of the immune system.

B Cells in Autoimmune Diseases

• B cells contribute to autoimmune diseases by starting, or continuing, an immune response against self (your own) tissues and cells​
• These B cells multiply and produce autoantibodies, antibodies against self-proteins, that attack healthy cells

B Cells in Blood Cancers

• B-cell lymphoma and lymphocytic leukemias are types of blood cancers that are caused by B cells​
• Lymphocytes that are no longer healthy or become abnormal (leukemia or lymphoma cells) are not able to fight infection very well​
• The number of these leukemia or lymphoma cells increases, leaving less room for healthy cells

Treatment Options​

• Certain autoimmune diseases and cancers can be treated using medicines that remove or destroy these disease-causing B cells
• Several B-cell depleting therapies are approved and/or used to treat these diseases, but there remains a need to develop more effective, less burdensome, and more accessible treatments for patients

SC291 and SC262 are hypoimmune allogeneic CAR T cell therapies being studied in clinical trials​

Donor (allogeneic) T cells are genetically modified to create SC291 and SC262 to:

• Attack and kill disease-causing B cells by targeting proteins, called CD19 and CD22, respectively, that are found specifically on B cells​
• Not attack other tissues or cells in your body, which can result in a condition known as “graft-versus-host disease”
• Prevent the CAR T cells from being rejected by your body’s immune system, which is why the therapy is referred to as “hypoimmune” CAR T cell therapy

SC291 and SC262 have been tested in preclinical in vitro (cell-based experiments) and in vivo (animal) studies before being studied in human clinical trials. Results from the preclinical studies support testing in clinical trials.

GLEAM clinical trial

A Phase 1 study evaluating SC291, a hypoimmune allogeneic CD19-directed CAR T cell therapy, in severe relapsed or refractory autoimmune diseases​

The trial is designed to study the possible risks and benefits of SC291 for autoimmune diseases.

• The GLEAM trial is open to patients with severe relapsed or refractory autoimmune diseases, including lupus nephritis, extrarenal systemic lupus erythematosus, and anti-neutrophil cytoplasmic antibody-associated vasculitis​
• Safety will be monitored throughout the trial​
• The amount of drug in the body after SC291 dosing will be measured (pharmacokinetics)​
• Specific biological markers (biomarkers) to assess potential treatment response will be measured​
• All participants will receive study drug; there is no placebo control in the GLEAM trial​
• More information about the GLEAM clinical trial, including site locations and investigators, can be found at: GLEAM clinical trial​

VIVID clinical trial

A Phase 1 study evaluating SC262, a hypoimmune allogeneic CD22-directed CAR T cell therapy, in relapsed and/or refractory non-Hodgkin lymphoma​

The trial is designed to study the possible risks and benefits of SC262 for certain types of blood cancers.

• The VIVID trial is open to patients with relapsed and/or refractory non-Hodgkin lymphoma​
• Safety will be monitored throughout the trial​
• The amount of drug in the body after SC262 dosing will be measured (pharmacokinetics)​
• Specific biological markers (biomarkers) to assess potential treatment response will be measured​
• All participants will receive study drug; there is no placebo control in the VIVID trial​
• More information about the VIVID clinical trial, including site locations and investigators, can be found at: VIVID clinical trial​

The role of regulatory agencies and ethics committees

Clearance to Start a Clinical Trial

If the preclinical (cell or animal studies) results suggest the study drug is ready to enter clinical trials, a request is submitted to regulatory agencies (called an Investigational New Drug (IND) Application).

They decide if the potential benefits of the study drug outweigh the possible risks and if it is ready to begin testing in the proposed clinical trial by reviewing:

• How the study drug is made (known as manufacturing)
• What the preclinical studies showed
• How the study drug will be tested in people (known as the clinical protocol)

After Clinical Testing

If the results from the clinical trials support pursuing approval of the study drug, the sponsor will submit a request to ask the regulatory agencies to consider approving the new drug for use (known as a Biological License Application [BLA]) .

The BLA includes all the efficacy and safety data generated, analyses of the data, and how the drug is manufactured.

Results from the clinical trials will be shared with the patient community through the clinical trial site, the investigator, medical and scientific communications, press releases, and clinicaltrial.gov postings.

Who can participate in a clinical trial?

• Each clinical trial has specific eligibility criteria (known as “inclusion and exclusion criteria”) that are a list of requirements that a trial participant must meet.
• Eligibility criteria are developed to minimize safety risks and to ensure that the clinical trial can answer its research question.
• The eligibility criteria are based on what is known about the condition and how the study drug may work.
• This means that not everyone living with a specific condition will be eligible to participate in the trial.
• You and your doctor will discuss criteria for enrollment into a clinical trial.

The National Institutes of Health provides patients, family members, and members of the public access to information on clinical trials through the website https://clinicaltrials.gov/

Finding a clinical trial that is right for you can be overwhelming. More information and resources are available for leukemia and lymphoma at https://www.lls.org/support-resources/clinical-trial-support-center-ctsc and for lupus at https://lupustherapeutics.org/lucin/.

Things to consider about participating in a clinical trial

• Deciding to participate in a clinical trial is personal and complex.
• The research and development process of any new treatment (“investigational drug” or “study drug”), including cell therapies, involve many clinical trials and can take years. These trials are conducted to find out if the potential benefits of the study drug outweigh the possible risks.
• Before someone can participate in a clinical trial, and whenever information about a trial significantly changes, a conversation between the investigator and study participant must take place with written acknowledgement. This is known as “informed consent”.
• The informed consent document includes details about the trial, what it means to participate in the trial, the potential benefits and possible risks (some of which are unknown), who to contact during the trial, and the rights of study participants.
• Ask about the different groups that may be included in the study, e.g. study drug group, control group, placebo group.
• Participation in a clinical trial may not benefit you and may have risks, but will contribute to moving science forward.
• You should consult with your healthcare provider for all treatment decisions.
• It is important to understand all your treatment options before deciding if joining a clinical trial is right for you.

Cell Therapy

• American Society of Gene & Cell Therapy (ASGCT) Patient Education
• American Society of Gene & Cell Therapy (ASGCT) Patient Education CAR T Basics

Drug Development

• US Food and Drug Administration Drug Approval Process

Clinical Studies

• Leukemia and Lymphoma Society. Clinical Trial Support Center
• The National Institutes of Health provides patients, family members, and members of the public access to information on clinical trials through the website https://clinicaltrials.gov/
  • GLEAM clinical trial​​
  • VIVID clinical trial 
• Leukemia and Lymphoma Society: Questions to ask your Healthcare Provider About Clinical Trials

Autoimmune Diseases​

• Lupus Research Alliance: Lupus Therapeutics Inc​
• Lupus Foundation of America​
• Vasculitis Foundation

Non-Hodgkin Lymphoma (NHL)

• National Cancer Institute Adult Non-Hodgkin Lymphoma-Treatment Patient Version
• Leukemia and Lymphoma Society Non-Hodgkin Lymphoma
• Lymphoma Research Foundation Non-Hodgkin Lymphoma

Chronic Lymphocytic Leukemia (CLL)

• National Cancer Institute Chronic Lymphocytic Leukemia Treatment-Patient Version
• Leukemia and Lymphoma Society Chronic Lymphocytic Leukemia

The Patient Story

• Human Answers to Your Cancer Questions