On June 10, 2022 Wugen, Inc., a clinical-stage biotechnology company developing a pipeline of off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, reported that new preclinical data demonstrating the enhanced anti-tumor properties of WU-NK-101, Wugen’s lead memory natural killer (NK) cell therapy product (Press release, Wugen, JUN 10, 2022, View Source [SID1234615883]). The data elucidate the unique cytokine-induced memory-like (CIML) phenotype of WU-NK-101 and further support its clinical development for acute myeloid leukemia (AML) and a range of solid tumor indications. The findings will be presented during a poster session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress in Vienna.

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"These data are foundational to our approach and confirm our development strategy as we advance WU-NK-101 for both AML and solid tumors," said Dan Kemp, Ph.D., President and Chief Executive Officer of Wugen. "Today’s presentation highlights key functional features of WU-NK-101: its unique CIML phenotype, enhanced metabolic fitness, and persistent cytotoxic activity, which is maintained even within the harsh immunosuppressive tumor microenvironment. Together, these data affirm our conviction in WU-NK-101 as a best-in-class allogeneic NK cell therapy. We are eager to continue development of WU-NK-101 and expect to advance into an initial clinical trial for patients with relapsed or refractory (r/r) AML followed by additional studies in solid tumor indications."

Today’s presentation highlighted the following:

WU-NK-101 cells have a unique CIML phenotype with improved activation, metabolic flexibility, and cytotoxicity compared to conventional natural killer cells (cNK).

In vivo activity of WU-NK-101 was confirmed in an AML THP-1 xenograft model, where both single- and multi-dose regimens effectively reduced tumor burden relative to vehicle controls. The data support a planned clinical trial of WU-NK-101 for patients with r/r AML.

WU-NK-101 also overcomes several limitations associated with NK cell therapy in solid tumors, with key features including enhanced metabolic fitness and adaptability and enhanced functionality in immunosuppressive TME conditions compared to cNK—functional characteristics supporting further development of WU-NK-101 in solid tumor indications.

The details of Wugen’s poster presentation at EHA (Free EHA Whitepaper) are as follows:

Title: WU-NK-101, An Allogeneic Memory NK Cell, for the Treatment of Relapse or Refractory (R/R) Acute Myeloid Leukemia (AML)
Session date and time: Friday, June 10, 2022, from 4:30 – 5:45 p.m. CEST
Abstract Number: P1426
Presenting Author: Jan Davidson-Moncada, M.D., Ph.D., Chief Medical Officer, Wugen

Additional meeting information can be found at www.ehaweb.org/congress.

About WU-NK-101

WU-NK-101 is a novel immunotherapy harnessing the power of memory natural killer (NK) cells to treat liquid and solid tumors. Memory NK cells are hyper-functional, long-lasting immune cells that exhibit enhanced anti-tumor activity and a cytokine-induced memory-like (CIML) phenotype. This rare cell population has a superior phenotype, proliferation capacity, and metabolic fitness that makes it better suited for cancer therapy than other NK cell therapies. Wugen is applying its proprietary MonetaTM platform to advance WU-NK-101 as a commercially scalable, off-the-shelf cell therapy for cancer. WU-NK-101 is currently in development for acute myelogenous leukemia (AML) and solid tumors.

On June 10, 2022 AbbVie (NYSE: ABBV) reported five-year follow-up results from the Phase 3 CLL14 trial, finding that over 60 percent of patients with previously untreated chronic lymphocytic leukemia (CLL) who had received one-year fixed-duration combination treatment of VENCLYXTO/VENCLEXTA (venetoclax) plus obinutuzumab (GAZYVA) continued to show longer progression-free survival (PFS) and higher rates of undetectable minimal residual disease (MRD) after four years off treatment (Press release, AbbVie, JUN 10, 2022, View Source [SID1234615852]).1 The findings were presented at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress (Abstract #S148).

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"Long-term data from the CLL14 trial show that the one-year fixed-duration combination regimen of venetoclax and obinutuzumab offers patients the possibility of four years of CLL treatment-free response without disease progression," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology clinical development, AbbVie. "Since its approval, this chemotherapy-free combination option has helped transform the therapeutic landscape for CLL."

Data shows that after more than five years of median follow-up (65.4 months), PFS remained significantly superior among patients treated with the VENCLYXTO/VENCLEXTA and obinutuzumab combination compared to the chlorambucil and obinutuzumab chemotherapy regimen (n=432; median NR vs 36.4 months; hazard ratio [HR] 0.35 [95% CI 0.26-0.46], p<0.0001). The therapies were administered for a fixed-duration of 12 months for VENCLYXTO/VENCLEXTA in combination with six cycles of obinutuzumab. At five years after randomization, the estimated PFS rate after one-year fixed-duration treatment was 62.6 percent for the VENCLYXTO/VENCLEXTA-based combination compared to 27.0 percent for the chlorambucil combination 1 The improvement in PFS was maintained across all risk groups, including patients with TP53 mutation/deletion and unmutated IGHV status.1

Among the secondary endpoints, patients were assessed for MRD in peripheral blood and/or bone marrow, using next generation sequencing. Undetectable MRD (uMRD) was defined as less than one CLL cell being identified per 10,000 lymphocytes sampled. Four years after treatment completion, 18.1 percent of patients treated with the VENCLYXTO/VENCLEXTA-based combination still had uMRD compared to 1.9 percent of patients in the chlorambucil combination study arm.1

The estimated overall survival (OS) rate was 81.9 percent in the VENCLYXTO/VENCLEXTA-based combination and 77.0 percent in the chlorambucil combination group (HR 0.72 [0.48-1.09], p=0.12) at five years after randomization.1

No new safety signals were observed in the five-year follow-up analysis. The most frequently occurring serious adverse reactions (>=2%) in patients receiving the VENCLYXTO/VENCLEXTA-based combination were pneumonia, sepsis, febrile neutropenia, and tumor lysis syndrome.1

"Four years following treatment completion, we are pleased to report that approximately three out of five patients who received the fixed-duration combination treatment with venetoclax have remained progression free," said Othman Al-Sawaf, M.D., investigator in the CLL14 study, hematologist-oncologist at the University Hospital Cologne in Germany, and study physician at the German CLL Study Group. "Additionally, it is notable that the population of patients who received chlorambucil combination was observed to have slightly more than twice the rate of progression events, compared to the patients who received the venetoclax combination."

VENCLYXTO/VENCLEXTA is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About the CLL14 Phase 3 Trial3,4,5
The prospective, multicenter, open-label, randomized Phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (DCLLSG), evaluated the efficacy and safety of a combined regimen of VENCLYXTO/VENCLEXTA and obinutuzumab (n=216) versus obinutuzumab and chlorambucil (n=216) in previously untreated patients with CLL and coexisting medical conditions (total Cumulative Illness Rating Scale [CIRS] score >6 or creatinine clearance <70 mL/min). The therapies were administered for a fixed-duration of 12 months for VENCLYXTO/VENCLEXTA in combination with six cycles of obinutuzumab. The trial enrolled 432 patients, all of whom were previously untreated, according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. Efficacy was based on PFS, as assessed by an independent review committee.

Key secondary endpoints were rates of MRD in peripheral blood and bone marrow, overall and complete response rates, MRD in complete response in peripheral blood and bone marrow, and overall survival.

In patients with CLL receiving venetoclax combination therapy with obinutuzumab, serious adverse reactions (ARs) were most often due to febrile neutropenia and pneumonia (5 percent each). The most common ARs (≥20 percent) of any grade were neutropenia (60 percent), diarrhea (28 percent), and fatigue (21 percent). Fatal ARs that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2 percent (4/212) of patients, most often from infection.

About VENCLYXTO (venetoclax)

VENCLYXTO (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.

Indication and Important VENCLYXTO (venetoclax) EU Safety Information4

Indications

Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).

Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy.

Venclyxto monotherapy is indicated for the treatment of CLL:

In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
Venclyxto in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.

Contraindications

Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumour lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as Venclyxto efficacy may be reduced.

Special Warnings & Precautions for Use

Tumour Lysis syndrome, including fatal events, has occurred in patients when treated with Venclyxto. For CLL and AML, please refer to the indication-specific recommendations for prevention of TLS in the Venclyxto summary of product characteristic (SmPC).

Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS. The risk of TLS is a continuum based on multiple factors, including comorbidities. Venclyxto poses a risk for TLS at initiation and during the dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venclyxto and at each dose increase.

Neutropenia (grade 3 or 4) has been reported. Complete blood counts should be monitored throughout the treatment period.

In patients with AML, neutropenia (grade 3 or 4) is common before starting treatment. The neutrophil counts can worsen with Venetoclax in combination with a hypomethylating agent. Neutropenia can recur with subsequent cycles of therapy. Dose modification and interruptions for cytopenias are dependent on remission status.

For CLL and AML, please refer to the indication-specific recommendations for dose modifications for toxicities in the Venclyxto SmPC.

Serious infections including sepsis with fatal outcome have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections should receive prompt treatment including antimicrobials and dose interruption or reduction as appropriate.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions

In CLL and AML CYP3A inhibitors may increase Venclyxto plasma concentrations.

In CLL, at initiation and dose-titration phase, Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, please refer to the recommendations for dose modifications in the Venclyxto SmPC.

In AML, please refer to the AML-specific recommendation for dose modifications for potential interactions with CYP3A inhibitors, in the VENCLYXTO SmPC.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.

CYP3A4 inducers may decrease Venclyxto plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions

CLL

The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab or rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (>=2%) were pneumonia and febrile neutropenia.

Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and Murano studies, respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions.

Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in CLL14, in 15% of patients treated with the combination of venetoclax and rituximab in Murano, and in 14% of patients treated with venetoclax in the monotherapy studies. The most common adverse reaction that led to dose interruptions was neutropenia.

AML

The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in combination with azacitidine or decitabine in the VIALE-A and M14-358, respectively, were thrombocytopenia, neutropenia, febrile neutropenia, nausea, diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and decreased appetite, haemorrhage, dizziness/syncope, hypotension, headache, abdominal pain, and anaemia.

The most frequently reported serious adverse reactions (≥5%) in patients receiving venetoclax in combination with azacitidine were febrile neutropenia, pneumonia, sepsis and haemorrhage. In M14-358, the most frequently reported serious adverse reactions (≥5%) were febrile neutropenia, pneumonia, bacteraemia and sepsis.

Discontinuations due to adverse reactions occurred in 24% of patients treated with venetoclax in combination with azacitidine in the VIALE-A study, and 26% of patients treated with venetoclax in combination with decitabine in the M14-358 study, respectively.

Dosage reductions due to adverse reactions occurred in 2% of patients in VIALE-A, and in 6% of patients in M14-358. Venetoclax dose interruptions due to adverse reactions occurred in 72% and 65% of patients, respectively. The most common adverse reaction that led to dose interruption (>10%) of Venetoclax in VIALE-A, were febrile neutropenia, neutropenia, pneumonia, and thrombocytopenia. The most common adverse reactions that led to dose interruption (≥5%) of venetoclax in M14-358 were febrile neutropenia, neutropenia/neutrophil count decreased, pneumonia, platelet count decreased, and white blood cell count decreased.

Special Populations

Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined.

For patients with severe (Child-Pugh C) hepatic impairment, a dose reduction of at least 50% throughout treatment is recommended.

Venclyxto may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.

This is not a complete summary of all safety information. See Venclyxto (venetoclax) SmPC at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete 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 June 10, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported the presentation of novel findings on biomarker development for IRAK4 inhibitor emavusertib, collaborative work from the University of Florida in primary CNS lymphoma (pCNSL), and clinical data from the TakeAim Leukemia and TakeAim Lymphoma studies at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress currently taking place in Vienna, Austria and online until June 12, 2022 (Press release, Curis, JUN 10, 2022, View Source [SID1234615866]).

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"We are delighted to share with our colleagues in Europe our findings regarding IRAK4’s previously undescribed localization in the nucleus of cancer cells. It appears that when IRAK4 is found in the nucleus with active NF-kB proteins p50 and p65, using a technique which we refer to as ‘triple staining,’ this triple nuclear presence is associated with better responses to emavusertib," said James Dentzer, President and Chief Executive Officer of Curis.

"Also at EHA (Free EHA Whitepaper) this year, collaborative work by Dr. Duane Mitchell’s team at the University of Florida is being presented on the potential role of emavusertib in treating pCNSL, including data on one patient who achieved a complete response following previous treatment with ibrutinib," Mr. Dentzer continued. "And finally, in addition to this foundational work on IRAK4 biology, we are presenting data from our TakeAim Lymphoma and TakeAim Leukemia studies as we continue to spread the word on IRAK4 and the utility of inhibiting this important target to our European colleagues."

Curis scientists have discovered previously unknown nuclear accumulation of IRAK4 selectively in acute myeloid leukemia (AML) cells whereas nuclear IRAK4 was not detectable in mature myeloid cells (#2609). IRAK4 nuclear accumulation is significantly correlated with NF-kB activation in bone marrow samples from de novo AML patients and in AML cell lines. The detection of IRAK4 and NF-kB (phospho-p50 and phospho-p65) using nuclear staining of blasts in AML bone marrow samples was defined as ‘triple-positive,’ and patients whose cells did not stain for the nuclear presence of any of the three markers were termed ‘triple-negative.’ Treatment with emavusertib led to a significant decrease in bone marrow blast count in AML patients whose bone marrow sample was triple-positive, whereas no significant decrease in bone marrow blast count was detected in triple-negative cases. The goal of the Company’s biomarker work is to develop a companion diagnostic for emavusertib that is broadly applicable and is intended to identify the patients most likely to benefit from emavusertib treatment.

Research from Curis collaborators at the University of Florida in pCNSL (#2715) show that, in a patient treated on the TakeAim Lymphoma study in the combination arm following a previous ibrutinib containing regimen, the combination of emavusertib and ibrutinib resulted in a complete response. The team also observed that IRAK-4 and NF-kB proteins have elevated expression levels in human pCNSL. Further, in preclinical work, the team showed that emavusertib achieves therapeutically relevant concentrations in brain parenchyma and shows single-agent activity in an aggressive model of pCNSL.

Also presented at the EHA (Free EHA Whitepaper) meeting were previously presented data from the TakeAim Leukemia (#3975) and TakeAim Lymphoma (#3875) studies. TakeAim Leukemia is being orally presented, and TakeAim Lymphoma is the subject of a poster at the meeting. The data from these studies were also presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting last week in Chicago.
About Emavusertib (CA-4948)
Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-κB protein complex. Additionally, third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, emavusertib was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS.

About TakeAim Lymphoma
The TakeAim Lymphoma study (NCT03328078) is a Phase 1/2 open-label, dose escalation, dose expansion clinical trial investigating emavusertib as monotherapy and in combination with ibrutinib in patients with R/R hematologic malignancies, such as non-Hodgkins’s lymphoma and other B cell malignancies. After dose escalation in both monotherapy and combination therapy to determine the recommended Phase 2 dose (RP2D), we plan to expand four cohorts for combination treatment: marginal zone lymphoma, activated b-cell diffuse large b-cell lymphoma, primary CNS lymphoma, and patients developing adaptive resistance to ibrutinib monotherapy. The goals of the study are to determine several parameters including safety, maximum tolerated dose (MTD), RP2D and signals of activity.

About TakeAim Leukemia
The TakeAim Leukemia study (NCT04278768) is a Phase 1/2 dose escalation and dose expansion study examining emavusertib use as both monotherapy and in combination with azacitidine or venetoclax in patients with R/R AML or high risk MDS. After dose escalation in both monotherapy and combination therapy to determine the recommended Phase 2 dose, we plan to expand five cohorts: monotherapy in AML patients with spliceosome and FLT3 mutations, monotherapy in patients with MDS and spliceosome mutations and combination therapy with azacitidine or venetoclax in patients without spliceosome or FLT3 mutations. The goals of the study are to determine several parameters including safety, maximum tolerated dose (MTD), RP2D and signals of activity.

On June 10, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the publication of clinical data across multiple programs at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress, being held June 9-12, 2022 (Press release, Autolus, JUN 10, 2022, View Source [SID1234615884]).

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Autolus will hold a conference call on Monday June 13 2022 at 7:30 am EST / 12:30 pm BST, which will include participation from; Dr. Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center; Dr. Kate Cwynarski, Chair UK T cell Lymphoma Group, Consultant Hematologist, University College London Hospital; and Autolus’ management team.

"We are excited to be presenting this first clinical data for two new product candidates, AUTO4 with its unique targeting approach for T cell lymphoma and AUTO1/22 a dual targeting CAR T product for the treatment of children with ALL," said Dr. Christian Itin, CEO of Autolus. "With obe-cel progressing towards pivotal data in the FELIX trial in adult patients with ALL, we are pleased to show obe-cel’s broader utility in B-NHL patients, mirroring the high level of activity and well manageable safety profile we have seen in previous trials."

"This year’s EHA (Free EHA Whitepaper) is an important meeting for Autolus with four presentations providing updates from ongoing clinical studies," said Dr. Martin Pule, Chief Scientific Officer of Autolus. "In an oral presentation we will present AUTO4 clinical data for the first time. These data suggest that AUTO4 has the potential to become an important therapeutic option for patients with T cell lymphoma. In a second presentation, we will present our finding from clinical testing of AUTO1/22. These data show that AUTO1/22 can induce remission in children with B-ALL, including in those whose disease was not successfully treated with commercial CAR T product. Further, data suggest that AUTO1/22 can prevent antigen escape. In two additional presentations, we demonstrate incremental obe-cel data in B-NHL and B-CLL, as well as some early data in PCNSL. Obe-cel continues to have consistent safety and efficacy data across these indications."

"As clinicians, we are always searching for new strategies to address unmet needs in aggressive blood cancers," said Dr. Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York. "T Cell Lymphomas are particularly challenging, and I’ve been following Dr. Pule’s strategy of CAR T targeting based on the mutually exclusive expressions of TRBC1 or TRBC2 with great interest. Any advance in bringing new effective therapies to patients with T cell lymphomas is of great importance."

Data presentations:

Title: Safety and preliminary efficacy findings of AUTO4, a TRBC1-targetting CAR, in relapsed/refractory TRBC1 positive selected T Cell Non-Hodgkin Lymphoma
Session Title: Gene therapy and cellular immunotherapy – Clinical 2
Session date and time: Saturday, June 11, 2022 16:30 – 17:45 CEST
Session room: Hall Strauss 1-2
Final Abstract Code: S261
Presenting Author: Kate Cwynarski
Conclusions: As of April 26 2022, 10 patients with TRBC1-positive r/r T-cell lymphoma (Peripheral T-cell lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell lymphoma (AITL), Anaplastic Large cell lymphoma (ALCL)) have been treated with AUTO4 in a Phase I dose escalation trial. Three patients had prior stem cell transplantation. After lymphodepletion with Flu/Cy, patients received either 25, 75, 225 or 450 x 106 CAR T cells. AUTO4 demonstrated a tolerable safety profile, with no patient experiencing any dose limiting toxicities, and no neurotoxicity/immune effector cell-associated neurotoxicity (ICANS) and no Grade 3 or higher infections. CRS was only seen at the highest dose level of 450 x 106 CAR T cells (Grade 3 in 1 patient; Grade 1-2 in 3 patients). As of 26 April 2022, 9 patients were evaluable for efficacy. At the highest dose level 3 of the 3 patients dosed achieved a complete metabolic remission (CMR) at 1 month. 2 of these patients remain in ongoing CMR by PET-CT at Month 3 and 6 respectively, whilst the 3rd relapsed at 3 months.
Title:Dual antigen targeting with co-transduced CD19/22 CAR T cells for relapsed/refractory ALL (AUTO1/22)
Session Title: Gene therapy and cellular immunotherapy – Clinical 1
Session date and time: Saturday, June 11, 2022 11:30 – 12:45 CEST
Session room: Hall Strauss 1-2
Final Abstract Code: S259
Presenting Author: Sara Ghorashian
Conclusions: As of May 27 2022, in 11 treated patients, we have reproducibly generated a product that is balanced in CD19 and CD22 CAR expression, with predominance of dual CAR T cells and having a mostly central memory phenotype. To date and in Kymriah-ineligible patients, AUTO1/22 has demonstrated a favorable safety profile. There have been no incidences of severe CRS, and one Grade 4 ICANS which was indistinguishable from chemotherapy-related leukoencephalopathy. We have seen excellent CAR T expansion, with only 4 patients losing CAR T persistence at the last follow up. Overall, 9 out of 11 patients achieved complete response, and there were 2 non-responders. Notably, 2 out of 3 patients with CD19-ve disease achieved complete response demonstrating the efficacy of the CD22 CAR. Two patients relapsed with CD19+CD22+ disease, a further patient had emergence of molecular MRD and all these events were associated with lack of CAR T Cell persistence. No antigen negative relapses were seen in responding patients. At a median follow up of 8.7 months, 6 of 9 responding patients were in MRD-negative complete remission (1-12 months) and the median duration of b-cell aplasia has not been reached.
Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory Primary CNS Lymphoma
Session Title: Poster session
Session date and time: Friday, June 10, 2022 – 16:30 – 17:45 CEST
Final Abstract Code: P1460
Presenting Author: Claire Roddie
Conclusions: Excellent AUTO1 expansion was observed in the peripheral blood by qPCR, with persistence in all treated patients at last follow-up. No grade >/=3 CRS was observed using IV or I-VEN AUTO1 administration. Two cases of grade 3 ICANS were reported following IV infusion. In the first case the patient had several neurological deficits that evolved despite ICANS treatment and were compatible with progressive PCNSL, as confirmed with the month 1 MRI scan. The second case was a patient whose neurological deficits improved with steroids/anakinra. Encouraging response rates were observed: of 6 patients evaluable for efficacy following IV AUTO1, the ORR was 4/6 (67%), with 2 CRs and 2 PRs. These four responding patients are without disease progression at last follow up. Two patients died from progressive PCNSL on study. Longer follow-up is needed and enrolment of additional patients is ongoing.
Title: Safety and efficacy findings of AUTO1, a fast off-rate CD19 CAR, in relapsed/refractory B-Cell Non-Hodgkin’s Lymphoma (B-NHL), and chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)
Session Title: Poster session
Session date and time: Friday, June 10, 2022 – 16:30 – 17:45 CEST
Final Abstract Code: P1459
Presenting Author: Claire Roddie
Conclusions: AUTO1 continues to display a favorable safety profile with no ICANS or Grade ≥ 3 CRS. Long term persistence of AUTO1 in the peripheral blood was demonstrated by qPCR. Of the 20 patients evaluable for efficacy, the overall response rate was 18/20 (90%). In the B-NHL cohorts the CRR was 16/17 (94%) (FL: 7/7, MCL: 3/3, DBCL: 6/7). In the CLL cohort a best response of a PR was achieved in 2/3 patients, notably both achieved MRD-negativity in their marrow and both remain in PR at 10 and 6 months respectively. Of the responding MCL, DLBCL, FL and CLL patients, 17/18 (94%) are without disease progression at last follow-up. One MCL patient relapsed six months following treatment and 1 FL patient died in CR from COVID-19. Longer follow-up and enrolment of additional MCL, FL, DLBCL and CLL patients is ongoing.
Conference Call
Management will host a conference call and webcast on June 13, 2022 at 7:30 am ET/12:30 pm BST to discuss the EHA (Free EHA Whitepaper) data. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website.

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID: 6594553. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID: 6594553.

On June 10, 2022 AbbVie (NYSE: ABBV) reported new data from Cohort 3 of its Phase 2 REFINE study of investigational navitoclax in combination with ruxolitinib in JAK inhibitor naïve patients with myelofibrosis (MF), a rare and difficult to treat blood cancer (Press release, AbbVie, JUN 10, 2022, View Source [SID1234615853]). These preliminary findings show spleen volume and symptomatic improvement in this cohort. These data are consistent with previously observed data from relapsed/refractory patients in Cohort 1a1 and will be shared in an oral presentation at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress (Abstract #S197).2

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REFINE is a Phase 2 non-randomized open-label multi-cohort study evaluating the safety and efficacy of navitoclax alone or in combination with ruxolitinib in MF.

"Current treatment options for myelofibrosis are limited and targeted toward controlling disease symptoms," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology clinical development, AbbVie. "Together with pre-clinical findings, early results of this study demonstrating anti-fibrosis activity of navitoclax in combination with ruxolitinib are promising. Specifically, the data findings regarding reduction in spleen volume, symptoms and bone marrow fibrosis help support the further exploration of disease modification in myelofibrosis."

The results presented at EHA (Free EHA Whitepaper) 2022 were from a preliminary analysis of 32 JAK inhibitor naïve MF patients from Cohort 3 of the Phase 2 REFINE trial (NCT03222609).2 The primary endpoint was spleen volume reduction of ≥35 percent (SVR35) from baseline at week 24.2 Key secondary endpoints include ≥50 percent reduction in total symptom score (TSS50) at week 24, anemia response and BMF reduction.2

In the results, SVR35 was achieved by 63 percent of evaluable patients at week 24 (20/32) and by 78 percent at any time on treatment (25/32).2 At week 24, 41 percent (11/27) of evaluable patients with measurable baseline symptoms reached TSS50; notably, 67 percent of patients (18/27) met this endpoint at any time during the study.2 In this cohort, 35 percent of evaluable patients, with available fibrosis grade at baseline and during the study, (9/26) achieved reduction in BMF by ≥1 grade at any time during the study with three patients experiencing ≥2 grade reductions in BMF.2 Additionally, 40 percent of patients evaluable for anemia response (6/15) experienced improvement in anemia, a common clinical feature of MF.2

Preliminary safety analysis identified no new safety signals. Thirty-one (97 percent) patients reported one or more adverse event (AE).1 The most common Grade ≥3 AEs were thrombocytopenia (47 percent), anemia (34 percent), and neutropenia (25 percent).1 Seven patients (22 percent) reported experiencing serious AEs.1 Three patients (9 percent) experienced an AE leading to navitoclax discontinuation and three patients (9 percent) reported an AE leading to ruxolitinib discontinuation.2

"These data reinforce the importance of early intervention in myelofibrosis and the potential to achieve improved clinical outcomes," said Francesco Passamonti, Full Professor of Hematology, University of Insubria and Chief, Hematology, Varee Hospital. "These preliminary results show good responses to combination therapy with navitoclax that may continue to improve over time."

About Navitoclax
Navitoclax is an investigational, oral BCL-XL/BCL-2 inhibitor. The BCL-2 family of proteins are known regulators of the apoptosis pathway.3

Navitoclax is not approved by the U.S. Food and Drug Administration (FDA) or any Health Authority worldwide at this time. Its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies.

AbbVie has an extensive late-stage clinical trial program for investigational navitoclax that is currently enrolling. For more information about enrolling in a clinical trial, please visit us here.

About the REFINE Study
REFINE is a multi-cohort, Phase 2, randomized, open-label, multicenter study evaluating the tolerability and efficacy of navitoclax alone or when added to ruxolitinib in patients with myelofibrosis (MF).4 The primary outcome measure is the percentage of patients who achieve Spleen Volume Reduction of greater than or equal to 35 percent (SVR35) from baseline to Week 24. Secondary outcomes measures include percentage of participants achieving 50 percent reduction in Total Symptom Score from baseline to Week 24 and change in grade of bone marrow fibrosis assessed according to the European Consensus Grading System.

Data presented at EHA (Free EHA Whitepaper) 2022 include preliminary safety and efficacy results from Cohort 3 of REFINE (n=32). Patients in Cohort 3 had primary or secondary MF with splenomegaly and had not received JAK-2 therapy or BET inhibitors prior to enrollment. Data presented at EHA (Free EHA Whitepaper) 2022 are representative of data from Cohort 3 of the REFINE study as of February 7, 2022.

Data included in the official EHA (Free EHA Whitepaper) 2022 Abstract Book are representative of data from Cohort 3 of the REFINE study as of October 4, 2021.

More information can be found on View Source (NCT03222609).

About Myelofibrosis
Myelofibrosis (MF) is a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Patients living with MF experience symptoms such as an enlarged spleen, fatigue, weakness, and severe anemia, that are often debilitating and greatly impact quality of life. MF also carries a risk of transformation to more aggressive disease such as acute myeloid leukemia.4

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