On December 6, 2020 AbbVie (NYSE: ABBV), reported results from a long-term integrated analysis of two Phase 3 clinical studies and additional pooled analysis evaluating the effect of IMBRUVICA (ibrutinib) based therapies for the first-line treatment of high-risk patients with chronic lymphocytic leukemia (CLL) (Press release, AbbVie, DEC 6, 2020, View Source [SID1234572260]). The totality of data featured at the virtual 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting continues to establish the treatment benefit of IMBRUVICA for CLL patients with or without high-risk disease.

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Results from an integrated analysis of two Phase 3 clinical trials (RESONATE-2 and iLLUMINATE) with up to 6.5 years of long-term follow-up investigating the use of IMBRUVICA-based therapies in patients with CLL/small lymphocytic lymphoma (SLL) with first-line treatment showed similar progression-free survival (PFS) and overall response rates (ORR) in patients with or without high-risk genomic features (Abstract #2220).1

"We’re excited to present long-term follow-up results at the ASH (Free ASH Whitepaper) congress across multiple studies, including our pivotal Phase 3 clinical trials RESONATE-2 and iLLUMINATE, which showed continued PFS and ORR benefits across high-risk patients with previously untreated CLL," said Danelle James, M.D., M.A.S., IMBRUVICA Clinical Development Lead, Pharmacyclics LLC, an AbbVie company.

Additionally, a pooled analysis across four clinical trials with up to 8 years of follow-up, including three Phase 3 studies (RESONATE-2, iLLUMINATE, E1912), and the Phase 2 PCYC-1122e study – sponsored by the National Heart, Lung, and Blood Institute (NHLBI) – showed that first-line treatment with IMBRUVICA-based therapies resulted in sustained, long-term efficacy with high 4-year PFS rates in high-risk CLL patients, defined as del(17p) or TP53 gene mutations (Abstract 2219).2

"The presence of del(17p) or TP53 gene mutation is a strong negative predictor of survival in patients with CLL, and testing for these markers is important so patients receive optimal therapy," said John Allan, M.D., assistant professor of medicine in the Division of Hematology and Medical Oncology and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and principal study investigator of the pooled analysis. "Although these patients remain at risk for disease progression, first-line treatment with ibrutinib based therapy may meaningfully improve the poor prognosis in this high-risk population."

The informCLL real-world prospective observational registry assessing treatment patterns will be featured in an oral presentation. Data from this real-world evidence study showed low testing rates for prognostic and biomarker features among patients with CLL.3 Further, when biomarker testing was performed, the selection of chemo-immunotherapy (CIT) continued for a considerable proportion of patients with del(17p)/TP53 mutational status, which is inconsistent with current guidelines (Abstract 547).4 As well, a retrospective, chart review study of real world patients featured as an oral presentation examined treatment patterns and time to next treatment (TTNT) in patients with CLL. Results showed high-risk patients with CLL treated with IMBRUVICA monotherapy had longer TTNT than those treated with CIT, and that IMBRUVICA therapy showed similar results in high risk and non-high-risk patients (Abstract 372).4

Abstract #2220: Outcomes of First-Line Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and High-Risk Genomic Features With up to 6.5 Years Follow-up: Integrated Analysis of Two Phase 3 Studies (RESONATE-2 and iLLUMINATE)

Poster Presentation: Sunday, December 6, 2020 at 7:00 a.m. PST

Data were presented from an integrated analysis of two Phase 3 studies evaluating IMBRUVICA-based therapy in the first-line treatment of CLL/SLL (RESONATE-2 and iLLUMINATE) to better understand outcomes in patients with various high-risk genomic features, including integrated fluorescence in situ hybridization (FISH) cytogenetics and single gene mutations.

In RESONATE-2 (NCT01722487), patients aged ≥65 years without del(17p) were randomized to single-agent IMBRUVICA or chlorambucil. In iLLUMINATE (NCT02264574), patients aged ≥65 years, or <65 years with coexisting conditions or del(17p)/TP53 mutation, were randomized to IMBRUVICA plus obinutuzumab or chlorambucil plus obinutuzumab. The integrated analysis included 498 patients treated with first-line IMBRUVICA -based or chlorambucil-based therapy (n=249 each) with a median follow-up of 49.1 months. At 42 months, PFS rates were higher across high-risk genomic subgroups in patients treated with IMBRUVICA (63 to 82 percent) compared to those receiving chlorambucil with or without obinutuzumab (6 to 34 percent), and consistent PFS benefit with IMBRUVICA was observed across all high-risk genomic subgroups.1 When comparing IMBRUVICA-treated patients with specific high-risk genomic features versus those without, results showed that PFS and ORR were comparable in the different subgroups, including patients with unmutated versus mutated immunoglobin heavy chain variable (IGHV) (PFS Hazard Ratio [HR], 1.79, 95% Confidence Interval [CI] 0.99-3.24) or mutated versus not mutated NOTCH1 (PFS HR, 1.05, 95% CI 0.65-1.69). 1 Results also showed improved outcomes for patients with del(17p)/TP53 mutated/BIRC3 mutated, the highest risk category (HR 1.05, 95% CI 0.54-2.04). 1,[5]

At a median duration of IMBRUVICA treatment of 35.7 to 43.8 months across these high-risk subgroups, there were no meaningful differences in the rates of treatment-emergent AEs of any grade or Grade 3 or higher AEs compared to those of the overall population. 1

Abstract #2219: Long-Term Efficacy of First-Line Ibrutinib Treatment for Chronic Lymphocytic Leukemia (CLL) With 4 Years of Follow-Up in Patients With TP53 Aberrations (del(17p) or TP53 mutation): a Pooled Analysis from 4 Clinical Trials

Poster Presentation: Sunday, December 6, 2020 at 7:00 a.m. PST

A pooled analysis of data across four studies to evaluate the long-term efficacy and safety of first-line IMBRUVICA-based therapy in patients with CLL bearing TP53 aberrations were presented. Eighty-nine patients with TP53 aberrations receiving first-line IMBRUVICA treatment were included in this pooled analysis. Median age was 65 years, and 69 percent of patients were male. Forty-five patients received IMBRUVICA as a single agent and 44 patients received IMBRUVICA in combination with an anti-CD20 agent.2

At 48 months, the PFS rate was 79 percent among these high-risk patients treated with IMBRUVICA-based therapy. 2 Median duration of IMBRUVICA treatment was 46 months. With a median follow-up of 50 months, median PFS was not reached (95% CI: 67 months to not estimable). 2

At the current follow-up, 46 percent of patients with TP53 aberrations remained on IMBRUVICA treatment. Reasons for treatment discontinuation were progressive disease (20 percent), study closure (12 percent), adverse events (AEs; 10 percent), withdrawal by patient (7 percent), death (3 percent), and other (1 percent). 2

Grade 3 or greater AEs of clinical interest with up to 8 years of treatment with IMBRUVICA were infection (22 percent), most commonly pneumonia (7 percent); hypertension (13 percent), atrial fibrillation (12 percent), and major hemorrhage (7 percent).2

Abstract #547: Real-World Prognostic Biomarker Testing, Treatment Patterns, and Dosing Among 1,461 Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) from the informCLL Prospective Observational Registry

Oral Presentation: Monday, December 7, 2020 at 8:15 a.m. PST

Results from the informCLL real-world prospective observational registry assessing treatment patterns in the era of novel agents were presented in an oral session.

The registry fully enrolled with 1,461 patients, of whom 855 (59 percent) were previously untreated and 606 (41 percent) were relapsed/refractory.4 Community-based practices enrolled 93 percent of the patients. 4 Patient demographics include a median age of 71 years; majority were male (64 percent), and 88 percent had an ECOG performance statue of 0/1.4 Median follow-up for previously untreated patients was 14.9 months and 15.3 months for relapsed/refractory patients.4

Results showed the most common index treatment was IMBRUVICA; and CIT was the next most widely used treatment regimen for one-third of patients.4 Data also showed that prognostic biomarker testing rates were poor, especially for TP53 and IGHV mutational status.4 Data from the informCLL study also indicates a ‘knowledge gap’ in terms of importance of prognostic marker testing and appropriate selection of therapies for patients with high-risk disease.4

Abstract #372: Clinical Outcomes Among Real-World Patients with Chronic Lymphocytic Leukemia (CLL) Initiating First-Line Ibrutinib or Chemoimmunotherapy (CIT) Stratified by Risk Status: Results from a US Retrospective Chart Review Study

Oral Presentation: Sunday, December 6, 2020 at 10:00 a.m. PST

Results from a retrospective study comparing clinical outcomes in high-risk and non-high-risk patients with CLL receiving IMBRUVICA compared to those receiving chemoimmunotherapy (CIT) as first-line therapy were presented.

The analysis was performed by evaluating medical records from more than 40 U.S. clinical practices, included 271 patients with high-risk disease and 245 patients with non-high-risk CLL.3 Baseline demographics and clinical characteristics were balanced within each pair of comparison groups. 3 The median (range) follow-up for high-risk patients treated with IMBRUVICA compared to CIT was 33.3 versus 35.3 months, respectively.3 Additionally, the median (range) duration of first-line therapy for patients treated with IMBRUVICA was 28.6 months compared to 5.5 months for patients treated with CIT. 3

The weighted analysis showed that high-risk patients treated with IMBRUVICA had significantly longer median TTNT and were 54 percent less likely to start a new treatment compared to high-risk patients treated with CIT (HR [95% CI]: 0.46 [0.34-0.62], p<0.01).3 During the available follow-up, more weighted high-risk patients treated with IMBRUVICA had only one line of treatment compared to weighted high-risk patients treated with CIT (74.7% vs 47.2%, respectively); more non-high-risk CIT patients had only one line of treatment compared to high-risk CIT patients (69.9% vs 45.8%, respectively); and more non-high-risk IMBRUVICA patients had only one line of treatment compared to high-risk IMBRUVICA patients (91.5% vs 81.7%, respectively).

Additionally, the majority of patients received a small molecular inhibitor therapy as second-line treatment. The most common second-line agents were IMBRUVICA monotherapy in the CIT groups (high-risk: 86.5%; non-HR: 83.7%) and venetoclax in the patients treated with first-line IMBRUVICA, either as monotherapy (high-risk: 37.5%; non-high-risk: 28.6%) or in combination with rituximab (high-risk: 28.1%; non-high-risk: 28.6%).

Results from the Kaplan-Meyer analysis showed that weighted high-risk IMBRUVICA patients had significantly longer median TTNT and were 54 percent less likely to start a new treatment compared to high-risk CIT patients (HR 95% CI: 0.46 [0.34-0.62]; p<0.01). For the high-risk patients receiving CIT versus non-high-risk patients receiving CIT, high-risk patients had a significantly shorter median TTNT and were 2.43 times more likely to start a new treatment (HR [95% CI]: 2.43 [1.58-3.47]; p<0.01). 3 No significant differences were noted in TTNT between high-risk and non-high-risk groups receiving IMBRUVICA, with median TTNT not reached (HR [95% CI]: 2.2 [0.96-4.96]; p=0.06). 3

About IMBRUVICA

IMBRUVICA (ibrutinib) is an oral, once-daily medicine that works differently than chemotherapy as it blocks a protein called Bruton’s tyrosine kinase (BTK). The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.6,7 By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.8

Since its launch in 2013, IMBRUVICA has received 11 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström’s macroglobulinemia (WM); previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.9

IMBRUVICA is now approved in more than 100 countries and has been used to treat more than 200,000 patients worldwide across its approved indications. IMBRUVICA is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

In early 2019, the National Comprehensive Cancer Network (NCCN ), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (IMBRUVICA) as a preferred regimen for the initial treatment of CLL/SLL. In February 2020, the NCCN Guidelines were updated to elevate IMBRUVICA with or without rituximab from other recommended regimens to a preferred regimen for the treatment of relapsed/refractory MCL. In September 2020, the NCCN guidelines were updated to elevate IMBRUVICA with or without rituximab as the only Category 1 preferred regimen for treatment-naïve WM patients.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 10 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com.

*Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

What is IMBRUVICA (ibrutinib)?

IMBRUVICA (ibrutinib) is a prescription medicine used to treat adults with:

Mantle cell lymphoma (MCL) who have received at least one prior treatment
Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion
Waldenström’s macroglobulinemia (WM)
Marginal zone lymphoma (MZL) who require a medicine by mouth or injection (systemic therapy) and have received a certain type of prior treatment
Chronic graft versus host disease (cGVHD) after failure of 1 or more lines of systemic therapy
It is not known if IMBRUVICA is safe and effective in children.

Important Side Effect Information

Before taking IMBRUVICA, tell your healthcare provider about all of your medical conditions, including if you:

have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA for any planned medical, surgical, or dental procedure.
have bleeding problems.
have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes.
have an infection.
have liver problems.
are pregnant or plan to become pregnant. IMBRUVICA can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA. Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA.
Females who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA and for 1 month after the last dose.
Males with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA and for 1 month after the last dose.
are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with IMBRUVICA and for 1 week after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA with certain other medicines may affect how IMBRUVICA works and can cause side effects.

How should I take IMBRUVICA?

Take IMBRUVICA exactly as your healthcare provider tells you to take it.
Take IMBRUVICA 1 time a day.
Swallow IMBRUVICA capsules or tablets whole with a glass of water.
Do not open, break or chew IMBRUVICA capsules.
Do not cut, crush or chew IMBRUVICA tablets.
Take IMBRUVICA at about the same time each day.
If you miss a dose of IMBRUVICA take it as soon as you remember on the same day. Take your next dose of IMBRUVICA at your regular time on the next day. Do not take extra doses of IMBRUVICA to make up for a missed dose.
If you take too much IMBRUVICA call your healthcare provider or go to the nearest hospital emergency room right away.
What should I avoid while taking IMBRUVICA?

You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA. These products may increase the amount of IMBRUVICA in your blood.
What are the possible side effects of IMBRUVICA?

IMBRUVICA may cause serious side effects, including:

Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA, and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.
Infections can happen during treatment with IMBRUVICA. These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA.
Decrease in blood cell counts. Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA, but can also be severe. Your healthcare provider should do monthly blood tests to check your blood counts.
Heart rhythm problems (ventricular arrhythmias, atrial fibrillation and atrial flutter). Serious heart rhythm problems and death have happened in people treated with IMBRUVICA, especially in people who have an increased risk for heart disease, have an infection, or who have had heart rhythm problems in the past. Tell your healthcare provider if you get any symptoms of heart rhythm problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, chest discomfort, or you faint. If you develop any of these symptoms, your healthcare provider may do a test to check your heart (ECG) and may change your IMBRUVICA dose.
High blood pressure (hypertension). New or worsening high blood pressure has happened in people treated with IMBRUVICA. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
Second primary cancers. New cancers have happened during treatment with IMBRUVICA, including cancers of the skin or other organs.
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.
The most common side effects of IMBRUVICA in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

diarrhea
tiredness
muscle and bone pain

rash
bruising

The most common side effects of IMBRUVICA in adults with cGVHD include:

tiredness
bruising
diarrhea

mouth sores (stomatitis)
muscle spasms
nausea

pneumonia

Diarrhea is a common side effect in people who take IMBRUVICA. Drink plenty of fluids during treatment with IMBRUVICA to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away.

These are not all the possible side effects of IMBRUVICA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of IMBRUVICA

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA for a condition for which it was not prescribed. Do not give IMBRUVICA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA that is written for health professionals.

Please click here for full Prescribing Information.

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world’s most widespread and debilitating cancers. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit View Source

On December 6, 2020 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported that it will present updated clinical data from two Phase II studies of bemcentinib in acute myeloid leukemia and high-risk myelodysplastic syndrome, in two poster sessions at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held virtually from 5-8 December 2020 (Press release, BerGenBio, DEC 6, 2020, View Source [SID1234572259]).

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Dr Sonja Loges will provide an update from the Company’s Phase II study of bemcentinib (BGBC003) in combination with low dose cytarabine (LDAC) in elderly previously treated, relapsed and refractory AML patients.

The data indicates that treatment with the bemcentinib-LDAC combination shows promising efficacy in relapsed patients who are unfit for intensive chemotherapy. Of 11 evaluable relapsed patients a response rate of 45% to date has observed. CR/CRi rate was 36% with durable responses observed, and clinical benefit observed in eight patients (73%) to date. Although the study is ongoing, patients remain on drug, with median treatment of 6.2 months in CR patients.

The Company is currently undertaking an in-depth translational research program aiming to identify predictive molecular and biological factors associated with response.

Dr Sonja Loges, Principal Investigator on the trial commented "The current prognosis for relapsed AML patients is very bleak, so we are pleased to see such a positive clinical benefit rate in relapsed second line patients with many patients remaining on drug for extended durations. We are currently undertaking an analysis to identify the suspected immune based factors that potentiate the effects of the drug in certain patients. We hope that this will enable us to identify specific biomarkers that will help us decide which patients may benefit most from treatment with bemcentinib."

Details of this Poster presentation as follows:

Title: The Combination of AXL Inhibitor Bemcentinib and Low Dose Cytarabine Is Well Tolerated and Efficacious in Elderly Relapsed AML Patients: Update from the Ongoing BGBC003 Phase II Trial (NCT02488408)

Date: Sunday, December 6, 2020

Session name: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II

Time: 7.00am – 3.30pm (Pacific Time) / 4.00pm – 12.30am (CET)

Abstract: View Source

An update will also be presented from the fully recruited investigator sponsored BERGAMO Phase II Trial investigating bemcentinib monotherapy in patients having relapsed treatment with hypomethelating agents (HMAs) with High Risk Myelodysplastic Syndromes (HR-MDS) or Acute Myeloid Leukemia (AML).

The primary endpoint of overall response rate (ORR) was met, with the MDS cohort achieving a 36% response rate, while 8.3% of patients with AML achieved stable disease. Three patients remain on drug, with median treatment exceeding 8 months. A comprehensive translational research program is ongoing to identify and verify soluble plasma biomarkers, including sAXL, that continue to be predictive of response.

Richard Godfrey, Chief Executive Officer of BerGenBio, said: "We are pleased to continue sharing updates from our phase II clinical studies assessing bemcentinib with the scientific and medical community. Data from both of the studies being presented at ASH (Free ASH Whitepaper) continue to show encouraging results in patients with a very poor prognosis with current treatment options. We believe these data provide further validation for our clinical development strategy in these indications as we prepare to progress bemcentinib into late stage randomised trials."

Details of this Poster presentations as follows:

Title: Efficacy and Safety of Bemcentinib in Patients with Myelodysplastic Syndromes or Acute Myeloid Leukemia Failing Hypomethylating Agents

Date: Saturday, December 5, 2020

Session name: 637 Myelodysplastic Syndromes – Clinical Studies: Poster I Hematology Disease Topics & Pathways: Diseases, Therapies, MDS, Myeloid Malignancies, Clinically relevant

Time: 7.00am – 3.30pm (Pacific Time) / 4.00pm – 12.30am (CET)

Abstract: View Source

Presentations will be made available at our website www.bergenbio.com under Investors/Presentations at the date of the conference.

-End-

About AML and the BGBC003 trial

Acute myeloid leukaemia (AML) is a rapidly progressing blood cancer. AML is the most common form of acute leukaemia in adults, where malignant AML blasts interfere with the normal functioning of the bone marrow leading to a multitude of complications like anaemia, infections and bleeding. AML is diagnosed in over 20,000 patients in the US annually and is rapidly lethal if left untreated. Successful treatment typically requires intensive chemotherapy or bone marrow transplantation, and relapse and resistance are common. Consequently, there is an urgent need for effective novel therapies in relapsed/refractory patients, particularly those that are ineligible for intensive therapy or bone marrow transplant.

The BGBC003 trial is a phase Ib/II multi-centre open label study of bemcentinib in combination with cytarabine (part B2) and low dose decitabine (part B3 & B5) in patients with AML who are unsuitable for intensive chemotherapy as a result of advanced age or existing-co-morbidities.

For more information please access trial NCT02488408 at www.clinicaltrials.gov.

About MDS

Myelodysplastic syndromes (MDS) are stem cell disorders characterised by a decreased ability of the bone marrow to produce normal blood cells and platelets. MDS is associated with increased risk of developing AML and immune dysfunctions are seen in patients both with lower and higher-risk MDS. Hypomethylating agents (HMAs) are the standard of care for patients with higher-risk myelodysplastic syndrome not eligible for intensive chemotherapy or allogeneic stem cell transplantation. However, the majority of patients do not respond to these agents or relapse, and face a dismal outcome with very limited treatment options available. Hence, there is an urgent need for novel therapies to treat MDS

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About Bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

On December 6, 2020 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, reported that the National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for ATG-010 (selinexor) combined with R-GDP (SR-GDP) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) (Press release, Antengene, DEC 6, 2020, View Source [SID1234572258]). The trial is a global Phase 2/3, multicenter, randomized study aiming to evaluate the safety and efficacy of ATG-010 in combination with R-GDP (SR-GDP) in patients with rrDLBCL (Code: XPORT-DLBCL-030).

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ATG-010 is a first-in-class and only-in-class oral selective inhibitor of nuclear export, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ: KPTI). In July 2019, the US Food and Drug Administration (FDA) approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM). After its initial approval of rrMM, FDA approved ATG-010 as a single-agent for the treatment of rrDLBCL in June 2020. In China, Antengene is conducting a registrational Phase 2 clinical trial to evaluate the efficacy and safety of ATG-010 in the treatment of patients with rrDLBCL who have received at least 2 but no more than 5 previous systemic regimens and the first patient was dosed in April 2020.

The Phase 2 part of the study aims to identify the optimal dose of ATG-010 (40mg or 60mg) in combination with R-GDP and will also evaluate the SR-GDP regimen against an active R-GDP comparator arm. The Phase 3 part of the study contains three arms and aims to evaluate the selected optimal dose of ATG-010 in combination with R-GDP for up to 6 cycles followed by continuous ATG-010 (SR-GDP→S) until disease progression versus the selected optimal dose of ATG-010 in combination with R-GDP for up to 6 cycles followed by placebo (SR-GDP→P) until disease progression and versus standard R-GDP with matching placebo for up to 6 cycles followed by placebo (PR-GDP→P) until disease progression. The study will be conducted at multiple international centers across 11 countries, located in China, U.S., Europe, Australia and other locations. Up to 501 patients will be enrolled and treated in the Phase 2/3 study.

"The submission of NDAs for ATG-010 in multiple APAC markets in the past few weeks has marked a significant milestone for Antengene as our lead product candidate, ATG-010, advances towards commercial stage. This IND acceptance of ATG-010 in a new therapy for rrDLBCL marks another important milestone for Antengene, demonstrating our commitment to bringing innovative oncology therapies to cancer patients worldwide." Dr. Jay Mei, Founder, Chairman and CEO of Antengene, commented, "We look forward to harnessing the power of Antengeners to extend the lives and improve the quality of life of patients by discovering, developing and commercializing novel therapies."

About ATG-010 (selinexor, XPOVIO)

ATG-010 (selinexor, XPOVIO) is a first-in-class and only-in-class oral selective inhibitor of nuclear export compound, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ: KPTI). In July 2019, the US Food and Drug Administration (FDA) approved ATG-010 in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved ATG-010 as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). ATG-010 is so far the first and only oral SINE compound approved by the FDA. ATG-010 is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene’s partner, Karyopharm Therapeutics, presented positive results from the Phase 3 randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral ATG-010 versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO study of ATG-010 in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

Antengene is conducting two registrational Phase 2 clinical trials of ATG-010 in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

On December 6, 2020 Bayer and Atara Biotherapeutics, Inc. (Nasdaq: ATRA) reported an exclusive worldwide license agreement and research, development and manufacturing collaboration for mesothelin-directed CAR T-cell therapies for the treatment of solid tumors (Press release, Bayer, DEC 6, 2020, View Source [SID1234572257]). The agreement includes the development candidate ATA3271, an armored allogeneic T-cell immunotherapy, and an autologous version, ATA2271, for high mesothelin-expressing tumors such as malignant pleural mesothelioma and non-small-cell lung cancer.

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Atara is a pioneer in allogeneic T-cell immunotherapy with industry-leading allogeneic cell manufacturing processes and CAR T technologies. The licensed technology leverages Atara’s novel, proprietary Epstein-Barr Virus (EBV) T-cell platform combined with CAR T technologies targeting mesothelin to improve efficacy, persistence, safety, and durability of response.

"This transaction is a fundamental element of Bayer’s new Cell & Gene Therapy strategy. It strengthens our development portfolio through allogeneic cell therapies and consolidates our emerging leadership in the field," said Wolfram Carius, Head of Bayer’s Cell & Gene Therapy Unit. "We look forward to collaborating with Atara to develop off-the-shelf CAR T-cell therapies for patients with difficult-to-treat cancers."

"This exciting collaboration between Atara and Bayer will accelerate the development of mesothelin-targeted CAR T-cell therapies for multiple solid tumors and helps us advance the power of our allogeneic cell therapy platform to patients as quickly as possible," said Pascal Touchon, President and CEO Atara. "Bayer’s proven track record in oncology global development and commercialization, and growing presence in cell and gene therapy, enhances Atara’s capabilities and complements our leading allogeneic T-cell platform."

Under the terms of the agreement, Atara will lead IND (Investigational New Drug)-enabling studies and process development for ATA3271 while Bayer will be responsible for submitting the IND and subsequent clinical development and commercialization. Atara will continue to be responsible for the ongoing ATA2271 phase 1 study, for which an IND filing has been accepted and the clinical trial has been initiated. Atara will receive an upfront payment of USD 60 million and is eligible to receive payments from Bayer upon achievement of certain development, regulatory and commercialization milestones totaling USD 610 million, as well as tiered royalties up to low double-digit percentage of net sales.

As part of the transaction, Atara will also provide translational and clinical manufacturing services to be reimbursed by Bayer. In addition, for a limited period of time, Bayer has a non-exclusive right to negotiate a license for additional Atara CAR T product candidates.

Atara Conference Call and Webcast Information

Atara will hold a conference call at 8:30 a.m. ET. Analysts and investors can participate in the conference call by dialing (888) 540-6216 for domestic callers and (734) 385-2715 for international callers, using the conference ID 3995182.

A live audio webcast can be accessed by visiting the Investors & Media – News & Events section of atarabio.com. An archived replay will be available on the Company’s website for 30 days following the live webcast.

About CAR-T cell therapy

T cells are a type of white blood cell that are critical in eliminating the body of abnormal and cancerous cells in healthy individuals. In cancer patients, these T cells frequently fail to either recognize or effectively engage cancer cells. CAR T-cell therapies involve engineering a human T cell to express a chimeric antigen receptor (CAR) that increases its ability to recognize cancer cells. These therapies use the immune system to fight cancer and have the potential to disrupt cancer care and potentially even provide a cure. Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors and is an attractive target for immune-based therapies, including CAR T therapy.

About Bayer’s new Cell & Gene Therapy (C&GT) Unit

In order to build up its presence in C&GT, Bayer is strengthening its internal C&GT capabilities. At the same time, the company is pursuing external strategic collaborations, technology acquisitions and licensing. The goal is to build robust platforms with broad application across different therapeutic areas. Strategically, Bayer focuses on selected areas of C&GT, such as stem cell therapies (with focus on induced pluripotent cells or iPSCs), gene augmentation, gene editing and allogeneic cell therapies in different indications. Leveraging external innovation together with the expertise of the teams at Bayer represents a key value-driver, especially in the highly dynamic and competitive field of C&GT. Bayer’s operating model for C&GT, where partners operate autonomously and are fully accountable to develop and progress their portfolio and technology, is essential for preserving their entrepreneurial culture and positions Bayer as a partner of choice. The role of Bayer’s C&GT Platform is to steer strategically, ensuring the different parts of the organization complement each other and combining the best in Biotech and Pharma know-how. As part of the Pharmaceuticals Division, the C&GT Platform will combine multiple backbone functions providing support across the entire value chain for the research and development of cell and gene therapies. This includes expertise in Research and Preclinical Development, CMC (Chemistry, Manufacturing and Controls), Clinical Development, Commercial, Strategy Implementation and Project Management. With a high level of flexibility, it will orchestrate operations from science to launch in order to generate and maintain a sustainable pipeline, with the goal to bring new products to market as fast as possible.

About Atara’s Mesothelin CAR-T Franchise

Two of Atara’s investigational CAR T immunotherapy programs, developed in collaboration with Memorial Sloan Kettering Cancer Center (MSK), target mesothelin—the autologous ATA2271 program and allogeneic ATA3271 program. Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors including mesothelioma, non-small cell lung cancer, ovarian cancer and pancreatic cancer.

Both ATA2271 and ATA3271 are engineered for use in solid tumors as they incorporate Atara’s novel inclusion of both a PD-1 DNR construct to overcome checkpoint inhibition and a 1XX costimulatory domain on the CAR (chimeric antigen receptor) to enhance expansion and functional persistence of the CAR T cells. ATA3271, the allogeneic version of this CAR T, leverages Atara’s EBV T-cell platform and is currently in IND-enabling studies. ATA2271, the autologous version has enrolled the first patient in an open-label, single-arm Phase 1 clinical study in November 2020.

On December 6, 2020 HighPassBio, an ElevateBio portfolio company dedicated to advancing novel targeted T cell immunotherapies, reported the ongoing Phase 1 trial of the company’s lead product candidate, an engineered T cell receptor (TCR) T cell therapy targeting HA-1 expressing cancer cells in an oral presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, HighPassBio, DEC 6, 2020, View Source [SID1234572256]). The Phase 1 clinical trial, which is being conducted by researchers at Fred Hutchinson Cancer Research Center, is designed to assess the feasibility, safety, and efficacy of this novel cell therapy in the treatment of leukemia following hematopoietic stem cell transplant (HSCT).

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"The prognosis for leukemia patients who’ve relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse," said Elizabeth Krakow, M.D., MSc., Assistant Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, principal investigator of the study, and presenting author. "We have observed early promising indicators of anti-leukemic activity following treatment in this trial. We are eager to expand the trial to additional patients as we continue to research the feasibility, safety, and efficacy of this approach."

The abstract for the presentation titled Phase 1 Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress, can be found on the ASH (Free ASH Whitepaper) website under the abstract number 137726.

To date, four patients, including one pediatric patient, have received a total of six infusions in the Phase 1 clinical trial. Patient characteristic data was shared in the oral presentation at ASH (Free ASH Whitepaper), including documented HA-1 TCR T cell persistence in blood and bone marrow up to 18 months. In some patients, clear in vivo anti-leukemic activity was observed at the first dose level, including a subject with aggressive, highly refractory T-ALL and early post-HCT relapse. No significant toxicities attributed to the T cells have been observed, including no infusion reactions or evidence of cytokine release syndrome or graft versus host disease.

The Phase 1 clinical trial is currently recruiting adult and pediatric patients who have residual disease or relapsed leukemia or related conditions following HSCT. As part of the trial, transplant patients and prospective donors may be recruited to participate in the genetic screening portion to determine eligibility. More details are available on clinicaltrials.gov under the study ID number NCT03326921.

About TCR-Engineered T Cell Therapy

A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the body’s immune system to respond to fight off and kill the tumor cells.

Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease.

Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patient’s native cells, and not by the cells from the stem cell transplant donor. HA-1, a known minor histocompatibility antigen, is expressed predominantly or exclusively on hematopoietic cells, including leukemic cells. There is evidence that T cells specific for HA-1 can induce a potent and selective antileukemic effect. HA-1 TCR T cell therapy is a new investigational immunotherapy for the management of post transplantation leukemia relapse.

About Leukemia post HSCT Treatment and the Risk of Relapse

Leukemia, a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, is the tenth most common type of cancer in the U.S. with an estimated 60,140 new cases and 24,400 deaths in 2016. Leukemia arises from uncontrolled proliferation of a specific type of hematopoietic (blood) cell that is critical for a functional immune system. As a result, when patients are given very high doses of chemotherapy to eradicate leukemic cells, most normal cells are killed as well, necessitating a transplant of hematopoietic stem cells from a donor to reconstitute the patient’s bone marrow and circulating hematopoietic cells. In some cases, the transplanted T cells from the donor can also recognize and eliminate the hematopoietic cells, including leukemia, from the recipient, thus preventing relapse. This can be described as a graft versus leukemia effect. Other hematologic disorders related to leukemia, like myelodysplastic syndrome (MDS), can also be treated in this way.

While HSCT can be curative, it is estimated that 25-50 percent of HSCT recipients relapse; leukemia relapse remains the major cause of allogeneic HSCT failure, and the prognosis for patients with post-HCT relapse is poor. Relapse occurs following allogeneic HSCT in approximately one-third of patients with acute leukemia who undergo the procedure, and most patients subsequently die of their disease.