Starting on subcutaneous EPKINLY¹

The purpose of this video is to provide information on EPKINLY product handling and instructions for dilution.

Your role in preparing EPKINLY is vital to patients and their care partners as key members of their care team. The recommended doses for EPKINLY include a zero point one six milligram priming dose, a zero point eight milligram intermediate dose, and a forty-eight milligram full dose. EPKINLY is administered according to the following 4-week dosing cycles. Administer EPKINLY until disease progression or unacceptable toxicity. Learn more about the Important Safety Information, including Boxed Warning for CRS and ICANS, at the end of this video.

Product availability should be used by staff to determine the patient's planned treatment schedule, including the administration times for premedication. Herein, we will give detailed instructions on how to properly store and handle EPKINLY. Before the dilution and preparation of EPKINLY: Store and transport EPKINLY refrigerated at two to eight degrees Celsius (thirty-six to forty-six degrees Fahrenheit)

• Do NOT freeze EPKINLY

Keep EPKINLY in the original carton to protect from light

• Do NOT shake EPKINLY

After the dilution and preparation of EPKINLY

• EPKINLY solution should be used immediately or stored in a refrigerator and protected from light for up to twenty-four hours at two to eight degrees Celsius (thirty-six to forty-six degrees Fahrenheit) from the time of preparation
• EPKINLY solution can be stored for twelve hours at room temperature from the start of dose preparation to administration. Minimize exposure to light
• Allow EPKINLY solution to equilibrate to room temperature before administration
• Discard unused EPKINLY solution beyond the allowable storage time and in accordance with local requirements

Now that you know how to properly store and handle EPKINLY, let's go over how to properly prepare EPKINLY for administration in to your patients.

EPKINLY is for subcutaneous injection only. This video will provide step-by-step instructions for safely preparing EPKINLY using an empty sterile vials method. Note: Certain doses of EPKINLY require dilution prior to administration. Follow the preparation instructions provided in this video, as improper preparation may lead to improper dose.

Here we will go through the necessary steps needed to prepare the EPKINLY priming dose using an empty sterile vials method.

Let's begin by preparing your priming dose dilution supplies.

In order to prepare the priming dose using the sterile empty vials method, you will need to first obtain a turquoise cap four milligram per zero point eight milliliter single dose vial of EPKINLY. It is important to remember that EPKINLY is a refrigerated product that will need to come to room temperature before dilution. Now while you wait for your EPKINLY vial to come to room temperature, you will need to assemble additional supplies that are needed to begin diluting and preparing the EPKINLY priming dose.

In addition to EPKINLY, you will need: Two vials of zero point nine percent sodium chloride for injection, two empty sterile vials between ten and twenty milliliters, and five syringes of varying sizes with needles for compounding. It is recommended you obtain one 1 milliliter syringe, two three milliliter syringes, one five milliliter syringe and one ten milliliter syringe to perform your dilution.

Lastly, you will need a marker for labeling empty vials, alcohol swabs or alcohol spray for cleaning the vials and maintaining aseptic technique, and a sharps container for disposing used syringes and needles. Note: All dilutions should be performed in a sterile hood using aseptic technique.

As a reminder, here is a compilation of all supplies you will need to assemble before you get started.

Now we will go through a simulation on how to prepare a zero point one six milligram priming dose of EPKINLY using empty sterile vials.

To prepare the zero point one six milligram priming dose, EPKINLY four milligram per zero point eight milliliter requires TWO dilutions with zero point nine percent sodium chloride for injection by a healthcare provider using aseptic technique. When diluting EPKINLY, use a new, appropriatley sized syringe and needle for each transfer step.

First, grab your two empty sterile vials and label the first empty vial "Dilution A".

Next, label your second empty vial "Dilution B".

Grab the four milligram per zero point eight milliliter EPKINLY vial with the turquoise cap that is now at room temperature.

Gently swirl the EPKINLY vial. DO NOT invert, vortex, or vigorously shake the vial.

In order to maintain aseptic technique, swab the EPKINLY vial three times in the same direction with an alcohol swab. Alternatively, the EPKINLY vial can also be sprayed with alcohol and allowed to dry before starting the dilution process. This aseptic technique will be repeated several times throughout the dilution process.

Swab the first empty vial labeled "Dilution A" three times in the same direction with an alcohol swab or spray with alcohol and allowed to dry.

Withdraw zero point eight milliliter of EPKINLY into a one milliliter syringe. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of EPKINLY.

Transfer the zero point eight milliliter of EPKINLY into the Dilution A vial. The EPKINLY vial is no longer needed and may be discarded. REMINDER: Once you have pierced an empty vial, you have equalized the pressure within that vial, so for compounding practices, you need to make sure that you maintain negative pressure within the vial.

When transfering the EPKINLY to the Dilution A vial, press all the way down, and as you're creating pressure in the syringe, be sure to withdraw the extra air in order to again maintain negative pressure. By maintaining negative pressure, you will prevent compound from being released from the vial.

Grab one vial of zero point nine percent sodium chloride for injection.

Swab the zero point nine percent sodium chloride vial three times in the same direction with an alcohol swab or spray with alcohol and allow to dry.

Withdraw four point two milliliters of zero point nine percent sodium chloride into a five milliliter syringe. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of sodium chloride.

Transfer four point two milliliters of zero point nine percent sodium chloride into the Dilution A vial.

When transfering the zero point nine percent sodium chloride to the Dilution A vial, press all the way down, and as you're creating pressure in the syringe, be sure to withdraw the extra air in order to again maintain negative pressure. By maintaining negative pressure, you will prevent compound from being released from the vial.

Gently swirl the Dilution A vial for thirty to forty-five seconds.

Next, grab the second empty vial labeled "Dilution B" and swab this vial three times in the same direction with an alcohol swab or spray with alcohol and allow to dry.

Withdraw two milliliters of solution from the Dilution A vial using a three milliliter syringe. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of solution from the Dilution A vial.

Transfer two milliliters of solution from the Dilution A vial into the Dilution B vial. REMINDER: Once you have pierced an empty vial, you have equalized the pressure within that vial, so for compounding practices, you need to make sure that you maintain negative pressure within this vial. The Dilution A vial is no longer needed and can be discarded.

Grab your second vial of zero point nine percent sodium chloride for injection and swab the zero point nine percent sodium chloride vial three times in the same direction with an alcohol swab or spray with alcohol and allow to dry.

Withdraw eight milliliters of zero point nine percent sodium chloride into a ten milliliter syringe. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of zero point nine percent sodium chloride.

Transfer eight milliliters of zero point nine percent sodium chloride in to the Dilution B vial.

Again, when transfering the zero point nine percent sodium chloride to the Dilution B vial, press all the way down, and as you're creating pressure in the syringe, you want to withdraw the extra air in order to again maintain that negative pressure. By maintaining negative pressure, you will prevent compound from being released from the vial.

Gently swirl the Dilution B vial for thirty to forty-five seconds.

Withdraw one milliliter of the solution from the Dilution B vial into a syringe intended for subcutaneous injection into the patient. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of solution from the Dilution B vial.

Label the syringe with the dose strength, zero point one six milligram, and the time of day. The syringe is now ready to be administered to the patient.

REMINDER:

• EPKINLY is for subcutaneous injection ONLY
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
• Each vial will be a "single-dose" vial. Once a needle has been inserted into the port of the vial and then withdrawn, the vial should be considered used. Multiple doses must not be withdrawn from one vial
• After preparing each dose, discard the single-dose vial and any unused portion of EPKINLY in accordance with local requirements

Here we will go through the necessary steps needed to prepare the EPKINLY intermediate dose using an empty sterile vial method.

Let's begin by preparing your intermediate dose dilution supplies.

In order to prepare the intermediate dose using the sterile empty vial method, you will need to first obtain a turquoise cap four milligram per zero point eight milliliter single dose vial of EPKINLY. It is important to remember that EPKINLY is a refrigerated product that will need to come to room temperature before dilution. Now while you wait for your EPKINLY vial to come to room temperature, you will need to assemble additional supplies that are needed to begin diluting and preparing the EPKINLY intermediate dose.

In addition to EPKINLY, you will need: One vial of zero point nine percent sodium chloride for injection, one empty sterile vial between ten and twenty milliliters, and three syringes of varying sizes with needles for compounding. It is recommended you obtain one 1 milliliter syringe, one three milliliter syringe, and one five milliliter syringe to perform your dilution.

Lastly, you will need a marker for labeling empty vials, alcohol swabs or alcohol spray for cleaning the vials and maintaining aseptic technique, and a sharps container for disposing used syringes and needles. Note: All dilutions should be performed in a sterile hood using aseptic technique.

As a reminder, here is a compilation of all supplies you will need to assemble before you get started.

Now we will go through a simulation on how to prepare a zero point eight milligram intermediate dose of EPKINLY using empty sterile vials.

To prepare the zero point eight milligram intermediate dose, EPKINLY four milligram per point eight milliliter requires ONE dilution with zero point nine percent sodium chloride for injection by a healthcare provider using aseptic technique. When diluting EPKINLY, use a new, appropriatley sized, syringe and needle for each transfer step.

First, grab your empty sterile vial and label the first empty vial "Dilution A".

Grab the four milligram per zero point eight milliliter EPKINLY vial with the turquoise cap that is now at room temperature.

Gently swirl the EPKINLY vial. DO NOT invert, vortex, or vigorously shake the vial.

In order to maintain aseptic technique, swab the EPKINLY vial three times in the same direction with an alcohol swab. Alternatively, the EPKINLY vial can also be sprayed with alcohol and allowed to dry before starting the dilution process. This aseptic technique will be repeated several times throughout the dilution process.

Swab the empty vial labeled "Dilution A" three times in the same direction with an alcohol swab or spray with alcohol and allow to dry.

Withdraw zero point eight milliliter of EPKINLY into a one milliliter syringe. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of EPKINLY.

Transfer the zero point eight milliliter of EPKINLY into the Dilution A vial. The EPKINLY vial is no longer needed and can be discarded. REMINDER: Once you have pierced an empty vial, you have equalized the pressure within that vial, so for compounding practices, you need to make sure that you maintain negative pressure within this vial.

When transfering the EPKINLY to the Dilution A vial, press all the way down, and as you're creating pressure in the syringe, be sure to withdraw the extra air in order to again maintain negative pressure. By maintaining negative pressure, you will prevent compound from being released from the vial.

Grab your vial of zero point nine percent sodium chloride for injection.

Swab the point nine percent sodium chloride vial three times in the same direction with an alcohol swab or spray with alcohol and allow to dry.

Withdraw four point two milliliters of zero point nine percent sodium chloride into a five milliliter syringe. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of sodium chloride.

Transfer four point two milliliters of zero point nine percent sodium chloride into the Dilution A vial.

When transfering the zero point nine percent sodium chloride to the Dilution A vial, press all the way down, and as you're creating pressure in the syringe, be sure to withdraw the extra air in order to again maintain negative pressure. By maintaining negative pressure, you will prevent compound from being released from the vial.

Gently swirl the Dilution A vial for thirty to forty-five seconds.

Withdraw one milliliter of the solution from the Dilution A vial into a syringe intended for subcutaneous injection into the patient. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of solution from the Dilution A vial.

Label the syringe with the dose strength, zero point eight milligram, and the time of day. The syringe is now ready to be administered to the patient.

REMINDER:

• EPKINLY is for subcutaneous injection ONLY
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
• Each vial will be a "single-dose" vial. Once a needle has been inserted into the port of the vial and then withdrawn, the vial should be considered used. Multiple doses must not be withdrawn from one vial
• After preparing each dose, discard the single-dose vial and any unused portion of EPKINLY in accordance with local requirements

Lastly, we will go through the necessary steps needed to prepare the EPKINLY full dose.

Let's begin by preparing your full dose supplies.

In order to prepare the full dose, you will need to first obtain an orange cap forty-eight milligram per zero point eight milliliter single dose vial of EPKINLY. It is important to remember that EPKINLY is a refrigerated product that will need to come to room temperature before use. EPKINLY forty-eight milligram per zero point eight milliliter does not need to be diluted prior to use. Now while you wait for your EPKINLY vial to come to room temperature, you will need to assemble additional supplies that are needed to begin preparing the EPKINLY full dose.

In addition to EPKINLY, you will need: One syringe used for administration to the patient and alcohol swabs or alcohol spray for cleaning the vials and maintaining aseptic technique. Note: EPKINLY full dose preparations should be performed in a sterile hood using aseptic technique.

As a reminder, here is a compilation of all supplies you will need to assemble before you get started.

Here we will go through a simulation on how to prepare a forty-eight milligram full dose of EPKINLY.

First, grab your forty-eight milligram per zero point eight milliliter EPKINLY vial with the orange cap that is now at room temperature.

Gently swirl the EPKINLY vial. DO NOT invert, vortex, or vigorously shake the vial.

In order to maintain aseptic technique, swab the EPKINLY vial three times in the same direction with an alcohol swab. Alternatively, the EPKINLY vial can also be sprayed with alcohol and allowed to dry before starting the dilution process. This aseptic technique will be repeated several times throughout the dilution process.

Withdraw zero point eight milliliter of EPKINLY into a syringe intended for subcutaneous injection into the patient. Note: It is important to remove all bubbles using proper technique to ensure that you are drawing up the appropriate volume of EPKINLY.

Label the syringe with the dose strength, forty-eight milligram, and the time of day. The syringe is now ready to be administered to the patient.

REMINDER:

• EPKINLY is for subcutaneous injection ONLY
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit
• Each vial will be a "single-dose" vial. Once a needle has been inserted into the port of the vial and then withdrawn, the vial should be considered used. Multiple doses must not be withdrawn from one vial
• After preparing each dose, discard the single-dose vial and any unused portion of EPKINLY in accordance with local requirements

INDICATION & IMPORTANT SAFETY INFORMATION
INDICATION
EPKINLY is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma (FL) grade 3B, after 2 or more lines of systemic therapy.
This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

• Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving EPKINLY. Initiate treatment with the EPKINLY step-up dosing schedule to reduce the risk of CRS. Withhold EPKINLY until CRS resolves or permanently discontinue based on severity.
• Immune effector cell-associated neurotoxicity syndrome (ICANS), including life-threatening and fatal reactions, can occur with EPKINLY. Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold EPKINLY until ICANS resolves or permanently discontinue based on severity.

Cytokine Release Syndrome (CRS)

• EPKINLY can cause CRS, including serious or life-threatening reactions. CRS occurred in 50% of patients in the clinical trial (37% grade 1, 16% grade 2, and 2.5% grade 3), with 49% of patients experiencing an event during cycle 1. Recurrent CRS occurred in 16% of patients. CRS occurred in 6% of patients after the 0.16 mg dose (cycle 1, day 1), 11% of patients after the 0.8 mg dose (cycle 1, day 8), 40% of patients after the 48 mg dose (cycle 1, day 15), and 4.5% of patients after the 48 mg dose (cycle 1, day 22). The median time to onset of CRS from the most recently administered EPKINLY dose across all doses was 24 hours (range, 0 to 10 days). The median time to onset after the first full 48 mg dose was 21 hours (range, 0 to 7 days). CRS resolved in 97% of patients; the median duration of CRS events was 1 day (range, 0 to 26 days).
• Initiate EPKINLY according to the step-up dosing schedule. Administer pretreatment medications to reduce the risk of CRS and monitor patients for potential CRS. See "Monitoring for CRS & ICANS" below.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

• EPKINLY can cause serious and fatal ICANS. ICANS occurred in 6.4% (10/157) of patients in the clinical trial (4.5% grade 1, 1.3% grade 2, one fatal event: 0.6%). Within cycle 1 of treatment with EPKINLY, 5.7% (9/157) of patients experienced an ICANS event. The median time to onset was 3 days (range, 1 to 13 days) after the most recent dose. The median duration of ICANS was 4 days (range, 0-8 days) and resolved in 90% of patients with supportive care.
• Monitor for potential ICANS. See "Monitoring for CRS & ICANS" below.

Monitoring for CRS & ICANS

• Following administration of the cycle 1, day 15 dosage of 48 mg, patients should remain within 30 minutes of a healthcare facility that can assess and manage potential CRS or ICANS for at least 24 hours.
• Signs and symptoms of CRS can include pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia.
• Signs and symptoms of ICANS can include confusional state, lethargy, tremor, dysgraphia, aphasia, and nonconvulsive status epilepticus.
• The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia.
• At the first signs or symptoms of CRS or ICANS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate. Advise patients to seek immediate attention should signs or symptoms of CRS or ICANS occur, and that the onset of ICANS may be delayed. Management of CRS or ICANS may require either temporary delay or discontinuation of EPKINLY.
• Patients with impaired consciousness or cognition should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.

Infections

• Serious, including fatal, infections have occurred with patients who received EPKINLY. In the clinical trial, serious infections, including opportunistic infections, were reported in 16% of patients treated with EPKINLY at the recommended dose with grade 3 or 4 infections in 15% and fatal infections in 1.9%. The most common grade 3 or greater infections were sepsis, COVID-19, urinary tract infection, pneumonia, and upper respiratory tract infection.
• Monitor patients for signs and symptoms of infection prior to and during treatment with EPKINLY and treat appropriately. Avoid administration of EPKINLY in patients with active infections.
• Prior to starting EPKINLY, provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis and consider prophylaxis for herpes virus.
• Withhold or consider permanent discontinuation of EPKINLY based on severity.

Embryo-Fetal Toxicity

• EPKINLY may cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose.

Adverse Reactions

• The most common (≥20%) adverse reactions were CRS, injection site reactions, fatigue, musculoskeletal pain, pyrexia, abdominal pain, nausea, and diarrhea. The most common grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

Lactation

• Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.

Please see accompanying full Prescribing Information or visit www.EPKINLYHCP.com.