On December 5, 2020 Legend Biotech Corporation (NASDAQ: LEGN) ("Legend Biotech"), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported the latest data results from the combined Phase 1b/2 CARTITUDE-1 study (NCT03548207) of ciltacabtagene autoleucel (cilta-cel), an investigational B-cell maturation antigen (BCMA) directed chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients with relapsed or refractory multiple myeloma (RRMM), sponsored by Janssen Research & Development, LLC (Press release, Legend Biotech, DEC 5, 2020, View Source [SID1234572248]). The data continued to show a very high overall response rate (ORR) that deepened over time, with 97 percent of patients achieving a response and 67 percent of patients achieving a stringent complete response (sCR) at a median follow-up of 12.4 months.1 The data were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #177) as an oral presentation.

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"A 97 percent response rate is extraordinary when you consider the patient population who, prior to cilta-cel, have generally experienced low response rates," said Deepu Madduri, M.D., Assistant Professor of Medicine, Hematology and Medical Oncology, Tisch Cancer Institute at Mount Sinai, New York, and principal CARTITUDE-1 study investigator. "Considering the early, deep and durable responses that we’ve seen at low-dose infusion of cilta-cel and its manageable safety profile, we look forward to further studying outpatient administration of cilta-cel in patients with multiple myeloma in earlier settings."

The trial included 97 patients treated with cilta-cel who received a median of six (range, 3-18) prior lines of therapy; 88 percent (n=85) were triple-refractory, 42 percent (n=41) were penta-refractory and 99 percent (n=96) were refractory to the last line of therapy.1 The median administered dose was 0.71×106 CAR+ viable T cells/kg and manufacturing of cilta-cel was successful for all patients. ORR per independent review was 97 percent, which included a sCR rate of 67 percent, very good partial response rate (VGPR) of 26 percent (VGPR or better, 93 percent) and partial response rate of 4 percent. Median time to first response was 1 month (range, 0.9-8.5) and responses were ongoing in 72 percent (n=70) of patients. Of 57 minimal residual disease (MRD) evaluable patients, 93 percent (n=53) were MRD negative at 10-5.1 Median progression-free survival (PFS) was not reached at median follow-up of 12.4 months (range, 1.5-24.9). The 12-month PFS rate was 77 percent (95 percent confidence interval [CI], 66-84) and the 12-month OS rate was 89 percent (95 percent CI, 80-94).1

The study also demonstrated a manageable safety profile for cilta-cel at the recommended Phase 2 dose.1 In the combined results, the most common hematologic adverse events (AEs) observed in the CARTITUDE-1 study were neutropenia (96 percent); anemia (81 percent); thrombocytopenia (79 percent); leukopenia (62 percent); and lymphopenia (53 percent).1 Cytokine release syndrome (CRS) of any grade was observed in 95 percent of patients, with a median duration of four days (range, 1-97), and 99 percent of which resolved within 14 days of onset. Of the 92 patients with CRS, most were Grade 1/2 (95 percent, n=87), 3 percent were Grade 3 (n=3), 1 percent was Grade 4 (n=1) and 1 percent was Grade 5 (n=1).1 The median onset of CRS was seven days (range, 1-12) post-infusion, with 89 percent (n=82) of patients experiencing CRS onset at day four or later, which is supportive of potential outpatient administration for cilta-cel. Total CAR-T cell neurotoxicity of any grade was observed in 21 percent (n=20) of patients, with Grade ≥3 neurotoxicity observed in 10 percent (n=10) of patients.1 Of these, Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed in 16 patients and generally occurred concurrently with CRS; other neurotoxicities were observed in 12 patients and generally occurred after resolution of CRS and/or ICANS (eight patients experienced both ICANS and other neurotoxicities).1 ICANS events were resolved in all patients with a median time to recovery of four days (range, 1-12).1 Other neurotoxicities were resolved in six patients at a median time of 75 days (range, 2-160) and were not resolved in six patients (one with ongoing toxicity, one died from neurotoxicity and four died due to other causes).1 Fourteen deaths were reported during the study: five due to disease progression, three due to adverse events unrelated to treatment (acute myelogenous leukemia [n=2], pneumonia [n=1]) and six due to adverse events related to treatment (sepsis and/or septic shock [n=2], CRS/HLH [n=1], neurotoxicity [n=1], respiratory failure [n=1], and lung abscess [n=1]).1

"We are encouraged by the see strong results from the CARTITUDE-1 study showing the potential of our lead product candidate cilta-cel to be a transformative treatment option for patients living with relapsed or refractory multiple myeloma," said Dr. Ying Huang, Chief Executive Officer and Chief Financial Officer of Legend Biotech. "We look forward to advancing this potentially life-saving treatment approach for patients in need."

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of ciltacabtagene autoleucel in adults with relapsed or refractory multiple myeloma, 99 percent of whom were refractory to the last line of treatment; 88 percent of whom were triple-class refractory(to at least 1 immunomodulatory drug [IMiD], 1 proteasome inhibitor [PI] and 1 anti-CD38 antibody).

The primary objective of the Phase 1b portion of the study, involving 29 patients, was to characterize the safety and confirm the dose of ciltacabtagene autoleucel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion of the study, involving 68 additional patients, is evaluating the efficacy of ciltacabtagene autoleucel with overall response rate as the primary endpoint.

About Cilta-cel

Cilta-cel is an investigational chimeric antigen receptor T (CAR-T) cell therapy, formerly identified as JNJ-4528 outside of China and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel. In addition to a Breakthrough Therapy Designation (BTD) granted in the U.S. in December 2019, cilta-cel received a PRIority MEdicines (PRiME) designation from the European Commission in April 2019 and BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.2 Although treatment may result in remission, unfortunately, patients will most likely relapse. 3 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.4 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.5,6 While some patients with multiple myeloma have no symptoms until later stages of the disease, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.7 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options.8

On December 5, 2020 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that new data from the pivotal Phase III MURANO and CLL14 studies support the efficacy of fixed-duration, chemotherapy-free Venclexta (venetoclax)-based combinations in certain people with chronic lymphocytic leukemia (CLL) and provide more evidence on the potential value of minimal residual disease (MRD) (Press release, Genentech, DEC 5, 2020, View Source [SID1234572246]). Data were presented at the all-virtual 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Saturday, December 5, 2020.

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"These results reinforce the long-term value of fixed-duration, chemotherapy-free Venclexta-based combinations in CLL, potentially offering patients a significant period of time without treatment following initial therapy," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "These data also reflect our ongoing commitment to accelerating clinical advancements for patients by exploring the novel endpoint minimal residual disease as a potential predictor of patient outcomes."

Five-year data from the pivotal Phase III MURANO trial continue to show sustained investigator-assessed progression-free survival (PFS) with Venclexta plus Rituxan (rituximab). Data, presented in an oral session, showed:

Venclexta plus Rituxan reduced the risk of disease progression or death by 81% (HR=0.19; 95% CI: 0.15, 0.26; p<0.0001) compared to bendamustine plus Rituxan (BR) in people with relapsed or refractory (R/R) CLL.
At the time of analysis, median overall survival (OS) had not been reached in either arm (HR=0.40; 95% CI: 0.26, 0.62), however, five-year OS was 82.1% in the Venclexta plus Rituxan arm, compared to 62.2% in the BR arm.
In the Venclexta arm, among the 130 patients who completed two years of treatment without progressive disease, 63.8% (n=83/130) had undetectable MRD (uMRD) levels at the end of treatment. In an analysis of this patient subgroup, uMRD was associated with improved progression-free survival. Undetectable MRD, sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.
No new safety events were reported in the study.
Data from the Phase III CLL14 study contributes to growing evidence regarding the potential of MRD measurements to predict future outcomes for certain people with previously untreated CLL who were treated with fixed-duration Venclexta plus Gazyva (obinutuzumab):

Patients with uMRD and a partial response (PR) had longer PFS than patients with detectable MRD and a complete response (CR).
In collaboration with Adaptive Biotechnologies, clonal growth rate, a measure for how quickly cancer cells grow, was analyzed using the next-generation sequencing Adaptive clonoSEQ Assay and insights were used to better understand the potential role of MRD in predicting outcomes. In this analysis, after treatment with fixed-duration Venclexta plus Gazyva, the estimated clonal growth rate was slower and lower, suggesting more effective MRD eradication in these patients compared to those treated with Gazyva plus chlorambucil. Early data suggest a correlation between MRD responses and PFS, which will be further evaluated by the study authors.
Exploring novel endpoints, such as MRD, is an important area of development for Genentech, which continues to investigate Venclexta in a robust clinical development program. This includes the Phase III CRISTALLO trial in previously untreated CLL, which uses MRD as a primary endpoint.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.

*Minimal residual disease (MRD) is a measure of the number of remaining cancer cells. Undetectable MRD (uMRD), sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.

About the MURANO Study

MURANO [NCT02005471] is a Phase III open-label, international, multicenter, randomized study evaluating the efficacy and safety of fixed-duration Venclexta (venetoclax) in combination with Rituxan (rituximab) compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukemia, with or without 17p deletion, who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival. Secondary endpoints included overall survival, overall response rate and complete response rate (with or without complete blood count recovery).

About the CLL14 Study

CLL14 [NCT02242942] is a randomized Phase III study evaluating the combination of fixed-duration Venclexta (venetoclax) plus Gazyva (obinutuzumab) compared to Gazyva plus chlorambucil in adult patients with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva alongside 12-month duration of chlorambucil (Arm B). Arm A started with an initial dosing of Gazyva followed by a five-week Venclexta dose ramp-up to help reduce the risk of tumor burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee, minimal residual disease (MRD) status, overall response rate, complete response rate (with or without complete blood count recovery), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety. MRD-negativity, or undetectable MRD, means no cancer can be detected using a specific and highly sensitive test, and was defined as less than one cancer cell in 10,000 leukocytes. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.

About CLL

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. In the United States, it is estimated that more than 20,000 new cases of CLL will be diagnosed in 2020. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.

In the United States, Venclexta has been granted five Breakthrough Therapy Designations by the U.S. Food and Drug Administration (FDA): one for previously untreated CLL, two for relapsed or refractory CLL and two for previously untreated acute myeloid leukemia.

Venclexta Indications

Venclexta is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
‒ are 75 years of age or older, or
‒ have other medical conditions that prevent the use of standard chemotherapy.

It is not known if Venclexta is safe and effective in children.

Important Safety Information

What is the most important information patients should know about Venclexta?

Venclexta can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids into their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS.

Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects. When restarting Venclexta after stopping for 1 week or longer, the patient’s doctor may again check for the risk of TLS and change the patient’s dose.

What patients should not take Venclexta?

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased TLS.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects.
Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:

Have kidney or liver problems.
Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
Have a history of high uric acid levels in the blood or gout.
Are scheduled to receive a vaccine. Patients should not receive a "live vaccine" before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients are instructed to not breastfeed during treatment with Venclexta and for 1 week after the last dose.
What to avoid while taking Venclexta:

Patients should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.

What are the possible side effects of Venclexta?

Venclexta can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta and may pause dosing.
Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta.
Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.

The most common side effects of Venclexta when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count; low platelet count; low red blood cell count; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of arms, legs, hands, and feet.

The most common side effects of Venclexta in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please see the Venclexta full Prescribing Information, including the Medication Guide, for additional Important Safety Information.

Rituxan Indications

Rituxan (rituximab) is a prescription medicine used to treat adults with:

Non-Hodgkin’s lymphoma (NHL): alone or with other chemotherapy medicines
Chronic lymphocytic leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide.
Important Safety Information:

Rituxan can cause serious side effects that can lead to death, including:

Infusion-Related Reactions: Infusion-related reactions are very common side effects of Rituxan treatment. Serious infusion-related reactions can happen during the patient’s infusion or within 24 hours after the patient’s infusion of Rituxan. The patient’s doctor should give the patient medicines before infusion of Rituxan to decrease the chance of having a severe infusion-related reaction.

Patients must tell their doctor or get medical help right away about any of these symptoms during or after an infusion of Rituxan:
Hives (red itchy welts) or rash
Itching
Swelling of the lips, tongue, throat, or face
Sudden cough
Shortness of breath, difficulty breathing, or wheezing
Weakness
Dizziness or feel faint
Palpitations (feel like the heart is racing or fluttering)
Chest pain
Severe Skin and Mouth Reactions: Patients must tell their doctor or get medical help right away about any of these symptoms at any time during treatment with Rituxan:
Painful sores or ulcers on the skin, lips, or in the mouth
Blisters
Peeling skin
Rash
Pustules
Hepatitis B Virus (HBV) Reactivation: Before receiving Rituxan treatment, the patient’s doctor will do blood tests to check for HBV infection. If the patient has had hepatitis B or is a carrier of hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems, including liver failure, and death. The patient’s doctor will monitor for hepatitis B infection during and for several months after the patient stops receiving Rituxan.

Patients must tell their doctor right away about worsening tiredness, or yellowing of the skin or white part of the eyes during treatment with Rituxan.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML.

Patients must tell their doctor right away about new or worsening symptoms or if anyone close to the patient notices these symptoms:
Confusion
Dizziness or loss of balance
Difficulty walking or talking
Decreased strength or weakness on one side of the body
Vision problems, such as blurred vision or loss of vision
What should patients tell their doctor before receiving Rituxan?

Before receiving Rituxan, patients should tell their doctor if they:

Have had a severe reaction to Rituxan or a rituximab product
Have a history of heart problems, irregular heartbeat, or chest pain
Have lung or kidney problems
Have had an infection, currently have an infection, or have a weakened immune system
Have or have had any severe infections including:
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Cytomegalovirus (CMV)
Herpes simplex virus (HSV)
Parvovirus B19
Varicella zoster virus (chickenpox or shingles)
West Nile Virus
Have had a recent vaccination or are scheduled to receive vaccinations. Patients should not receive certain vaccines before or during treatment with Rituxan
Have any other medical conditions
Are pregnant or plan to become pregnant. Patients must talk to their doctor about the risks to the patient’s unborn baby if receiving Rituxan during pregnancy. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan and for 12 months after the last dose of Rituxan. Patients should talk to their doctor about effective birth control. Patients should tell their doctor right away if they become pregnant or think that they are pregnant during treatment with Rituxan
Are breastfeeding or plan to breastfeed. It is not known if Rituxan passes into the breast milk. Do not breastfeed during treatment and for at least 6 months after the last dose of Rituxan
Are taking any medications, including prescription and over-the-counter medicines, vitamins, and herbal supplements
What are the possible side effects of Rituxan?

Rituxan can cause serious side effects, including:

Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells. TLS can cause the patient to have:
Kidney failure and the need for dialysis treatment
Abnormal heart rhythm
TLS can happen within 12 to 24 hours after an infusion of Rituxan. The patient’s doctor may do blood tests to check for TLS. The patient’s doctor may give medicine to help prevent TLS. Patients must tell their doctor right away if they have any of the following signs or symptoms of TLS:

Nausea
Vomiting
Diarrhea
Lack of energy
Serious Infections: Serious infections can happen during and after treatment with Rituxan, and can lead to death. Rituxan can increase the patient’s risk of getting infections and can lower the ability of the patient’s immune system to fight infections. Types of serious infections that can happen with Rituxan include bacterial, fungal, and viral infections. After receiving Rituxan, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these patients with low antibody levels developed infections. People with serious infections should not receive Rituxan. Patients must tell their doctor right away if they have any symptoms of infection:
Fever
Cold symptoms, such as runny nose or sore throat that do not go away
Flu symptoms, such as cough, tiredness, and body aches
Earache or headache
Pain during urination
Cold sores in the mouth or throat
Cuts, scrapes, or incisions that are red, warm, swollen, or painful
Heart Problems: Rituxan may cause chest pain, irregular heartbeats, and heart attack. The patient’s doctor may monitor the patient’s heart during and after treatment with Rituxan if they have symptoms of heart problems or have a history of heart problems. Patients must tell their doctor right away if they have chest pain or irregular heartbeats during treatment with Rituxan.
Kidney Problems: especially if the patient is receiving Rituxan for NHL. Rituxan can cause severe kidney problems that lead to death. The patient’s doctor should do blood tests to check how well their kidneys are working.
Stomach and Serious Bowel Problems That Can Sometimes Lead to Death: Bowel problems, including blockage or tears in the bowel can happen if the patient receives Rituxan with chemotherapy medicines. Patients must tell their doctor right away if they have any stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan.
The patient’s doctor will stop treatment with Rituxan if they have severe, serious, or life-threatening side effects.

What are the most common side effects during treatment with Rituxan?

Infusion-related reactions
Infections (may include fever, chills)
Body aches
Tiredness
Nausea
Other side effects include:

Aching joints during or within hours of receiving an infusion
More frequent upper respiratory tract infections
These are not all of the possible side effects with Rituxan.

Please see the Rituxan full Prescribing Information, including the Medication Guide, for additional Important Safety Information at View Source

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Gazyva Indications

Gazyva (obinutuzumab) is a prescription medicine used:

With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.
Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life threatening, including:

Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.
Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort.
Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva.
Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.
Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP.
Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections.
Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced.
The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81 percent), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within 6 months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness, and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86 percent) or marginal zone lymphoma (14 percent). The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.
Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.
Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit View Source

On December 5, 2020 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that it has acquired from Orsenix, LLC (Orsenix) all of its assets related to SY-2101, formerly known as ORH-2014, a novel oral form of arsenic trioxide (ATO) (Press release, Syros Pharmaceuticals, DEC 5, 2020, View Source [SID1234572245]). SY-2101 represents a strategic opportunity to leverage Syros’ expertise and capabilities to advance its growing footprint in hematologic disorders, with a targeted clinical-stage drug candidate that has the potential to dramatically reduce the treatment burden of a standard-of-care regimen for newly diagnosed acute promyelocytic leukemia (APL).

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"It’s rare to talk about cures in cancer," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "The IV formulation of ATO is part of a treatment regimen that cures most APL patients, but it is extremely burdensome with lengthy infusions over a nearly yearlong course of treatment. We believe an oral form that offers similar efficacy while dramatically reducing the treatment burden on these patients could quickly become a new standard-of-care. SY-2101 is also highly complementary to our efforts with SY-1425 in AML and MDS, positioning us for potential new drug applications for both programs in 2024. With the strategic financing announced today, we believe we are well-funded to advance our growing portfolio of product candidates across multiple patient populations to accelerate our vision of becoming a fully integrated biopharmaceutical company."

A Potential New Standard-of-Care Therapy

SY-2101 is in development for the treatment of APL, a subtype of acute myeloid leukemia (AML) defined by a fusion of the RARA and PML genes. An intravenously administered formulation of ATO is approved for use in combination with All-Trans-Retinoic-Acid (ATRA) in newly diagnosed APL and, while curative in approximately 80-90% of patients, its administration requires up to 140 two- to four-hour infusions over the typical course of induction and consolidation treatment.

Because SY-2101 is dosed orally once daily, it has the potential to become the standard-of-care frontline therapy for APL by providing comparable efficacy with a substantially more convenient option that reduces the treatment burden on patients, improving access, and lowering costs to the healthcare system. In a Phase 1 clinical trial, led by investigators at the M.D. Anderson Cancer Center, SY-2101 demonstrated bioavailability, pharmacokinetic (PK) exposures similar to IV ATO, and a generally well-tolerated safety profile.

Clinical Development Plans for SY-2101

Syros plans to initiate a dose confirmation study of SY-2101 in the second half of 2021. Following confirmation of a dose that demonstrates comparable PK to IV ATO, Syros intends to initiate a registration-enabling Phase 3 trial in patients with newly diagnosed APL in 2022. Based on interactions between Orsenix and the U.S. Food and Drug Administration (FDA), Syros believes molecular complete response rate and event-free survival in comparison to historical control data with IV ATO would support accelerated and full approval, respectively. If successful, Syros believes it could file a New Drug Application (NDA) with the FDA in 2024.

SY-2101 has orphan drug designation in the United States for the treatment of APL and Europe for the treatment of AML.

Acquisition Details

Under the terms of the asset purchase agreement, Syros has acquired all assets related to the development and commercialization of SY-2101, including intellectual property, clinical and preclinical data, the regulatory dossier, and product inventory. Syros has made an upfront cash payment of $12 million to Orsenix. In addition, Orsenix is eligible to receive a $6 million regulatory milestone related to the development of SY-2101 in APL and commercial milestones of up to $10 million. Orsenix is also eligible to receive single-digit million milestone payments related to the development of SY-2101 in indications other than APL.

Financing Details

Syros also announced today that it has entered into a definitive agreement for the sale of its equity securities in a private placement to a group of institutional accredited investors led by Bain Capital Life Sciences with participation from Ally Bridge Group, Omega Funds, OrbiMed, EcoR1 Capital, and Samsara BioCapital. The agreement provides for the sale of an aggregate of 10,312,500 shares of Syros’ common stock and, in lieu of shares of common stock, pre-funded warrants (Pre-Funded Warrants) to purchase an aggregate of 1,000,000 shares of common stock, and accompanying warrants (Warrants) to purchase an aggregate of up to 2,828,125 additional shares of common stock (or Pre-Funded Warrants in lieu thereof) at a price of $8.00 per share and accompanying Warrant (or $7.99 per Pre-Funded Warrant and accompanying Warrant). The price per Pre-Funded Warrant and accompanying Warrant represents the price of $8.00 per share and accompanying Warrant to be sold in the private placement, minus the $0.01 per share exercise price of each such Pre-Funded Warrant. The exercise price of the Warrants is $11.00 per share, or if exercised for a Pre-Funded Warrant in lieu thereof, $10.99 per Pre-Funded Warrant (representing the Warrant exercise price of $11.00 per share minus the $0.01 per share exercise price of each such Pre-Funded Warrant). The Warrants are exercisable at any time during the period beginning six months following the closing date of the private placement and ending on the fifth anniversary of the closing. The Pre-Funded Warrants are exercisable at any time after their original issuance and will not expire. The gross proceeds from the sales of common stock and Pre-Funded Warrants are expected to be $90.5 million, before deducting offering expenses. The private placement is expected to close on or about December 8, 2020, subject to the satisfaction of customary closing conditions.

The securities to be sold in the private placement have not been registered under the Securities Act of 1933, as amended (Securities Act), or any state or other applicable jurisdiction’s securities laws, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any offer, solicitation or sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful.

Updated Financial Guidance

As a result of these transactions, Syros expects to have sufficient funds for planned operating expenses and capital expenditure requirements into the second half of 2022.

Conference Call Information

Syros will host a conference call today at 4:30 p.m. ET to discuss its acquisition of SY-2101, as well as the new data for SY-1425, which were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

To access the live conference call, please dial 866-5954538 (domestic) or 636-812-6496 (international), and refer to conference ID 1264464. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation.

About Acute Promyelocytic Leukemia

APL is a well-defined subset of AML caused by the formation of an abnormal fusion gene, PML/RARA. This fusion gene leads to the overproduction of immature white blood cells called promyelocytes and the underproduction of healthy blood cells. Signs, symptoms and complications of APL include abnormal bleeding and bruising, anemia, fatigue, and increased risk of infection. APL makes up about 10% of AML cases, with an annual incidence of approximately 2,000 patients in the United States and Europe.

On December 5, 2020 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported new clinical data from its Phase 2 trial evaluating SY-1425, its first-in-class selective retinoic acid receptor alpha (RARα) agonist, in combination with azacitidine in two acute myeloid leukemia (AML) patient populations (Press release, Syros Pharmaceuticals, DEC 5, 2020, View Source [SID1234572244]). The data is being presented today in oral presentations at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. In a separate poster presentation on Monday, Syros will present translational data highlighting the potential of SY-1425 to benefit newly diagnosed unfit AML patients who may be resistant to the standard-of-care combination of venetoclax plus azacitidine.

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"The data that continue to emerge from the Phase 2 trial of SY-1425 are compelling," said Stéphane De Botton, M.D., Head of Acute Myeloid Malignancies at Institut Gustave Roussy and a clinical investigator in the trial. "SY-1425 in combination with azacitidine demonstrates high response rates, rapid onset of action, meaningful durability and favorable tolerability in RARA-positive newly diagnosed unfit AML patients. Despite recent advances, one-third of unfit AML patients still don’t respond to the standard-of-care regimen in the upfront setting and what we are now learning is that most of these patients may be RARA-positive. Taken together, these data support the potential of SY-1425 to become an important targeted therapy for RARA-positive AML patients, as well as for patients with a closely related hematologic malignancy known as higher-risk myelodysplastic syndrome."

"The new data presented today strengthen our conviction that SY-1425 has the potential to become the foundation of care for all RARA-positive patients," said David A. Roth, M.D., Chief Medical Officer of Syros. "Based on these results, we are excited to launch our planned registration-enabling Phase 3 trial in newly diagnosed higher-risk MDS patients, which puts us on track for a potential new drug application in 2024, and a randomized Phase 2 clinical trial evaluating SY-1425 as part of a triplet regimen with venetoclax and azacitidine in newly diagnosed unfit AML patients."

Promising New Data from Phase 2 Trial of SY-1425 in RARA-positive AML
Syros presented new data from its fully enrolled Phase 2 trial evaluating the safety and efficacy of SY-1425 in combination with azacitidine in newly diagnosed AML patients who are not suitable candidates for standard chemotherapy, as well as in RARA-positive relapsed or refractory (R/R) AML patients.

Mature Data in Newly Diagnosed Unfit AML
As of October 1st, 51 newly diagnosed unfit AML patients, including both RARA-positive and RARA-negative patients, were eligible for a safety analysis. Eighteen RARA-positive were evaluable for clinical response. In those patients, the data showed that:

Overall response rate (ORR) was 67% (12/18), with a composite CR rate of 61%, (11/18) including nine patients (50%) achieving a complete response (CR), two patients (11%) achieving a complete response with incomplete blood count recovery (CRi).
89% (8/9) of CRs were deep molecular or cytogenetic CRs.
Responses were seen across AML risk groups, including patients with mutations that are typically associated with poor outcomes.
Median time to initial response was 1.2 months.
Median duration of response was 10.8 months, and median overall survival (OS) among patients who achieved a CR or CRi was 18 months.
86% (6/7) of patients who were transfusion dependent at baseline became transfusion independent, and 67% (12/18) of patients achieved or maintained transfusion independence.
SY-1425 in combination with azacitidine was generally well-tolerated with no evidence of increased toxicity relative to either as a single agent, including rates of myelosuppression that were comparable to single-agent azacitidine.
Syros will also present new translational data demonstrating that most RARA-positive newly diagnosed unfit AML patients have a monocytic disease phenotype that is highly correlated with resistance to upfront treatment with venetoclax and azacitidine. These data suggest that the RARA biomarker not only selects for patients who are more likely to respond to treatment with SY-1425 but also for patients who are less likely to respond to treatment with venetoclax and azacitidine.

Data in Relapsed or Refractory AML
As of October 1st, 28 RARA-positive R/R AML patients were eligible for safety analysis and 21 were evaluable for clinical response. In those patients, the data showed:

ORR was 19% (4/21), consisting of one CRc, two CRi and one MLFS.
In HMA and venetoclax naïve patients, the ORR was 43% (3/7 patients).
Median OS was 5.9 months.
30% (6/20) achieved or maintained transfusion independence, including 27% (3/11) of patients who were transfusion dependent at baseline.
SY-1425 in combination with azacitidine was also generally well-tolerated in this patient population.
Advancing SY-1425 in Newly Diagnosed HR-MDS and Unfit AML
Based on the encouraging clinical activity and favorable safety and tolerability profile of SY-1425 in combination with azacitidine as well as an assessment of ongoing areas of high unmet need within the evolving treatment landscape, Syros plans to advance SY-1425 in combination with azacitidine into a registration-enabling Phase 3 trial in RARA-positive newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients. HR-MDS is a hematologic malignancy that is closely related to AML, and as in AML, about 30 percent of HR-MDS patients are RARA-positive.

Based on feedback from the U.S. Food and Drug Administration, Syros plans to enroll approximately 190 RARA-positive newly diagnosed HR-MDS patients in the double-blind placebo-controlled trial, randomized 2:1 to receive SY-1425 in combination with azacitidine or placebo with azacitidine, respectively. The primary endpoint of the trial will be the CR rate, which, depending on the data outcome, could support accelerated or full approval in this patient population. Syros expects to initiate the Phase 3 trial in the first quarter of 2021.

In addition, Syros plans to advance SY-1425 in combination with venetoclax and azacitidine in RARA-positive newly diagnosed unfit AML patients. The trial is designed with a single-arm safety lead-in to confirm the dosing regimen of the triplet to be used in the randomized portion of the Phase 2 trial, which will evaluate the safety and efficacy of SY-1425 in combination with venetoclax and azacitidine compared to venetoclax and azacitidine in approximately 80 patients randomized 1:1. The trial will also evaluate the triplet as a salvage therapy in patients who don’t respond to venetoclax and azacitidine. Syros expects to initiate the Phase 2 trial in the second half of 2021.

Conference Call Information
Syros will host a conference call today at 4:30 p.m. ET to discuss these data, as well as its acquisition of SY-2101, a clinical-stage drug candidate for the treatment of acute promyelocytic leukemia, from Orsenix, LLC, which was also announced today.

To access the live conference call, please dial 866-595-4538 (domestic) or 636-812-6496 (international), and refer to conference ID 1264464. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation.

On December 5, 2020 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for blood cancers and serious hematologic diseases, reported in an oral presentation the updated and expanded results from a Phase 1 clinical study of GDA-201, an investigational, natural killer (NK) cell-based cancer immunotherapy for the treatment of patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is being held virtually December 5–8 (Press release, Gamida Cell, DEC 5, 2020, View Source [SID1234572243]).

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GDA-201 was well-tolerated and no dose-limiting toxicities were observed in 35 patients (19 with NHL and 16 with MM). The data show that therapy using GDA-201 with monoclonal antibodies demonstrated significant clinical activity in heavily pretreated patients with advanced NHL. Of the 19 patients with NHL, 13 complete responses and one partial response were observed, with an overall response rate of 74 percent and a complete response rate of 68 percent. The maximum tolerated dose was not achieved, as no dose limiting toxicities were observed in patients who received the maximum target dose (2 x 108 cells/kg).

"Data from an expanded group of patients in this Phase 1 clinical study for GDA-201 show that NK cell therapies continue to exhibit impressive therapeutic potential to treat relapsed and refractory patients with lymphomas, while maintaining a favorable safety profile," said Veronika Bachanova, M.D., Ph.D., Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota and principal investigator of the study. "Despite recent advancements in therapies for patients with hematologic malignancies, too many patients progress to develop refractory or resistant disease. I look forward to the continued clinical development of this novel investigational therapy."

NK cell immunotherapies are thought to offer tremendous potential for transforming the care of hematologic malignancies. With GDA-201, Gamida Cell is pioneering a novel approach that harnesses the power of its cell expansion technology to improve antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells.

"These additional results again show that GDA-201 has striking signs of efficacy and safety in patients with heavily pre-treated NHL," said Julian Adams, Ph.D., chief executive officer of Gamida Cell. "With these results in hand, we plan to initiate a Phase 2 clinical study, with the goal of submitting an IND in 2021."

GDA-201 Phase 1 Clinical Data

The presentation, "Results of a Phase 1 Trial of GDA-201, Nicotinamide-Expanded Allogeneic Natural Killer (NK) Cells in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma," described results from the Phase 1 clinical study of GDA-201 in heavily pre-treated patients with advanced NHL and MM. Preliminary results from this study were presented at the 2019 ASH (Free ASH Whitepaper) Annual Meeting.

In the study, cell therapy using GDA-201 with monoclonal antibodies was shown to be safe; there were no dose-limiting toxicities, neurotoxic events, confirmed cytokine release syndrome, graft versus host disease or marrow aplasia. Overall survival and progression-free survival at one year in the NHL cohort suggest durable disease control, with a median follow-up of ten months (range 1–28 months). The most common adverse events were decreased neutrophil count, febrile neutropenia, anemia and low platelet counts.

In the NHL cohort, durable complete responses were observed in patients with both follicular and diffuse large B cell lymphoma, with an overall response rate of 74 percent. Future development of GDA-201 may include cryopreservation and the exploration of multiple treatment cycles in a multi-center Phase 2 trial in patients with NHL.

About GDA-201

Gamida Cell applied the capabilities of its NAM-based cell expansion technology to develop GDA-201, an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. GDA-201 is in Phase 1 development through an investigator-sponsored study in patients with refractory non-Hodgkin lymphoma and multiple myeloma.1 For more information on the clinical study of GDA-201, please visit www.clinicaltrials.gov.

GDA-201 is an investigational therapy, and its safety and efficacy have not been established by the U.S. Food and Drug Administration or any other health authority.

About the NAM Therapeutic Platform

Gamida Cell’s proprietary NAM-based cell expansion platform is designed to enhance the number and functionality of donor cells in culture, enabling the creation of potentially transformative therapies that move beyond what is possible with existing approaches. The NAM therapeutic platform leverages the unique properties of nicotinamide to enable the expansion of multiple cell types — including stem cells and natural killer (NK) cells — with appropriate growth factors to maintain the cells’ original phenotype and potency. This can enable the administration of a therapeutic dose of cells with the potential to improve patient outcomes.