Changing the possible for patients

What is Sana doing? What is cell therapy?

Cell therapy is the utilization of intact, live cells in a patient to treat a disease. An example of a cell therapy is an autologous CAR T cell therapy.

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.

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 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. These cells are modified to make them into CAR T cells, which enables them to recognize, attack, and destroy cancer cells when given to patients.
• For patients with cancer, the immune system is typically not able to recognize, attack, and destroy cancer cells on its own. 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 collected from the patient’s or donor’s blood and are modified to make them CAR T cells. These modifications allow the CAR T cells to recognize a protein on the surface of cancer cells, which causes them to attack and destroy the cancer cells.
• Different cancers can have different proteins on their cell surface, so CAR T cells are made to be specific to a cancer type. The CAR T cells are then administered to the patient.

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 – utilizing immune cells – but current therapies have limitations that may prevent this therapy from reaching its full potential. Research at Sana focuses on helping these therapies reach their potential for patients.

Currently approved CAR T cell therapies utilize 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 only at specialty cancer centers
• 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 non-cancer 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 cancer cells

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 immune rejection by the patient and attack and destroy cancer cells. T cells are isolated from a healthy donor and are modified to (A) avoid immune rejection by the patient’s immune system and (B) attack and kill cancer cells using the following steps:

1. Delete production of proteins on the donor T cells that look foreign to the patient’s immune system
2. Increase production of another protein that signals the patient’s immune system to not attack the CAR T cells
3. Add specialized receptors to the donor T cell that both recognize cancer cells and signal to the T cell to kill the cancer

Sana’s hypoimmune CAR T cell platform enables simultaneous manufacturing for many patients, and Sana’s CAR T cell therapies are ready for immediate “off-the-shelf” use.

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 cancer 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

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.

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

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/

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.

SC291 is a CD19-directed hypoimmune allogeneic CAR T cell therapy being studied in a clinical trial to see if it is safe and effective for the treatment of B-cell cancers

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

• Attack and kill B-cell cancers by targeting a protein called CD19 that is 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 SC291 from being rejected by your body’s immune system, which is why the therapy is referred to as “hypoimmune” CAR T cell therapy

SC291 has 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 SC291 in clinical trials.

Sana’s clinical trial

ARDENT Clinical Trial: A Phase 1 study evaluating SC291, a hypoimmune allogeneic CD19-directed CAR T cell therapy, in relapsed and/or refractory B-cell malignancies

The trial is designed to study the possible risks and benefits of SC291 in cancer patients.

• The ARDENT trial is open to patients with relapsed and/or refractory B-cell malignancies including large B-cell lymphoma and chronic lymphocytic leukemia
• 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) and radiologic scans to assess potential treatment response will be measured
• All participants will receive study drug; there is no placebo control in the ARDENT trial
• More details about the ARDENT clinical trial can be found at: ARDENT clinical trial

What is Non-Hodgkin Lymphoma (NHL)?

• NHL is used to describe a group of related blood cancers including diffuse large B-cell lymphoma (DLBCL).
• NHL subtypes grow and spread at different rates. Indolent lymphoma tends to grow and spread slowly and has few signs and symptoms. Aggressive lymphoma grows and spreads quickly and has signs and symptoms that can be severe.
• Treatments for indolent and aggressive NHLs are different so it is important to understand the subtype of the NHL diagnosis.

What is Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL)?

• In CLL, too many blood stem cells become abnormal lymphocytes (leukemia cells) that are not able to fight infection very well. As the number of leukemia cells increase in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This can lead to infection, anemia, and easy bleeding.
• CLL signs and symptoms include swollen lymph nodes, fatigue, shortness of breath, anemia, bruising easily, and frequent infections.
• CLL may be slow-growing or fast-growing, and treatments options may differ depending on the diagnosis.

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/
• Leukemia and Lymphoma Society: Questions to ask your Healthcare Provider About Clinical Trials

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