On December 13, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that preclinical data from two of their Innate Cell Engager (ICE) programs at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) (Press release, Affimed, DEC 13, 2021, View Source [SID1234596964]). The poster presentations included preclinical proof-of-concept data on AFM28, for which Affimed recently revealed the target and indication. The program is in development for the treatment of Acute Myeloid Leukemia and other CD123+ hematologic malignancies. The second poster presentation provided data on the activity of AFM13 pre-complexed to NK cells after cryopreservation, demonstrating the potential to develop AFM13 as an off-the-shelf chimeric antigen receptor (CAR)-like NK cell product.

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Preclinical characterization of the ICE AFM28

The novel ICE AFM28 is designed to target CD16A on innate immune cells and CD123 on tumor cells in relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). CD123 is almost universally expressed on leukemic blasts and leukemic stem cells (LSCs) and thereby represents a promising target in both indications.

The results revealed that target cell lysis via NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), even at low CD123 expression, was more pronounced compared to conventional anti-CD123 antibodies. In addition, AFM28 showed a 100-fold more potent NK cell activation in an ex vivo analysis, compared to Fc-enhanced IgG1 antibodies. When compared with a CD123-targeting T cell-engaging bispecific antibody, AFM28 activity was associated with substantially lower levels of inflammatory cytokine release suggesting low risk of cytokine release syndrome. In support of these findings, administration of AFM28 to cynomolgus monkeys induced the effective depletion of CD123+ target cells and was well tolerated.

AFM28 is currently being prepared for clinical evaluation. The properties of the preclinical characterization make it an interesting candidate for combination approaches with allogeneic NK cell products.

"There is an urgent need for relapsed or refractory AML and MDS patients and targeting the innate immune system – either alone or in combination with adoptive NK cells – holds promise for these patients," said Dr. Arndt Schottelius, CSO of Affimed. "Our data suggests that AFM28 engages NK cells to lyse CD123-positive leukemic blasts and leukemic stem cells. This is a critical step in achieving long-lasting remissions."

Cryopreservation of NK cells pre-complexed with innate cell engagers (CAR-like NK cells)

Pre-complexing NK cells with the ICE AFM13 generates chimeric antigen receptor (CAR)-like NK cells. Our preclinical assays demonstrate that anti-tumor efficacy of AFM13 pre-complexed NK cells was comparable to NK cells that were combined, though not pre-complexed with AFM13. Furthermore, the data showed that tumor cell lysis was enhanced compared to a Fc-enhanced antibody approach.

Retaining biological activity and specificity after cryopreservation is a prerequisite to enable the development of pre-complexed off-the-shelf CAR-like NK cell products. Our results confirmed that the efficacy of tumor cell lysis by AFM13-pre-complexed NK cells, was virtually unaffected after one cycle of cryopreservation at -80°C.

"The data are the basis to develop an off-the-shelf precomplexed NK cell product of our ICE molecules and mark an important milestone," said Dr. Arndt Schottelius, CSO of Affimed. "This is especially encouraging as we recently announced very promising data of the Phase 1-2 study at The University of Texas MD Anderson Cancer Center that evaluates AFM13 pre-complexed with NK cells in patients with CD30-positive lymphomas revealing a 100% objective response rate in 13 patients who received the recommended phase 2 dose."

The poster will additionally be featured on December 15 at 5:00 pm ET in the virtual poster walk on Natural Killer Cell-Based Immunotherapy which can be accessed via the following link: View Source

The full posters are available on Affimed’s website under "Publications & Posters". For more details about the ASH (Free ASH Whitepaper) Virtual Annual Meeting please visit: View Source

About AFM28

AFM28, a tetravalent, bispecific CD123- and CD16A-binding ICE developed on Affimed’s ROCK platform, is designed to bring a new immunotherapeutic approach to patients with CD123+ myeloid malignancies, including acute myeloid leukemia and myelodysplastic syndrome (MDS). It engages NK cells to initiate tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC), even at low CD123 expression levels. Clinical development is planned as both monotherapy and in combination with allogeneic NK cells in patients with relapsed/refractory CD123+ leukemias.

About AFM13

AFM13 is a first-in-class ICE that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating NK cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides (REDIRECT). The study is actively recruiting, and additional details can be found at www.clinicaltrials.gov (NCT04101331).

In addition, The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored phase 1 trial in combination with cord blood-derived allogeneic NK cells in patients with relapsed/refractory CD30-positive lymphomas (NCT04074746).

On December 13, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported updated data from the ongoing Phase 1/2 clinical trial of MB-106, a CD20-targeted, autologous CAR T cell therapy for patients with relapsed or refractory B-cell non-Hodgkin lymphomas ("B-NHLs") and chronic lymphocytic leukemia ("CLL") (Press release, Mustang Bio, DEC 13, 2021, View Source [SID1234596962]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Research Center ("Fred Hutch").

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The data presented in a poster session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting ("ASH2021") by Mazyar Shadman, M.D., M.P.H., Associate Professor, Clinical Research Division of Fred Hutch and a physician at Seattle Cancer Care Alliance, included efficacy and safety data from patients who were treated following a major cell manufacturing modification (n=20). Five dose levels were used during the study: 1 x 105, 3.3 x 105, 1 x 106, 3.3 x 106 and 1 x 107 cells/kg. Durable responses were observed in a wide range of hematologic malignancies including follicular lymphoma, diffuse large B-cell lymphoma, CLL, and Waldenstrom’s macroglobulinemia. An overall response rate ("ORR") of 95% and complete response ("CR") rate of 65% was observed in all patients across all dose levels. In patients with follicular lymphoma (n=15), the ORR was 93% and the CR rate was 73%. Robust CAR-T expansion and persistence was also observed. At the 28-day evaluation, a favorable safety profile was observed in all 20 patients, with no patients experiencing grade 3 or 4 cytokine release syndrome or immune effector cell‐associated neurotoxicity syndrome.

Mazyar Shadman, M.D., M.P.H., commented, "We are extremely pleased with the ongoing favorable safety profile and complete and durable responses with the current manufacturing process of MB-106, our third generation fully human CD20-targeted CAR T cell therapy for a mostly outpatient treatment of a wide range of relapsed or refractory hematologic malignancies. Given its safety and efficacy, CD20-targeted CAR T cell therapy has potential as an adoptive immunotherapy that could be utilized instead of, or in sequence with, CD19 CAR T cell therapy. Enrollment for this study remains robust for patients with CD20+ B-NHLs and CLL, including patients with prior CAR T treatment."

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, "The updated data presented by Dr. Shadman at ASH (Free ASH Whitepaper)2021 expand on the compelling clinical activity of MB-106 in patients with relapsed or refractory B-cell hematologic malignancies. We are enthusiastic about the responses observed and look forward to the continued advancement of our CD20-targeted CAR T cell therapy program. We expect to enroll the first patient under Mustang’s MB-106 investigational new drug trial for patients with B-NHLs and CLL early next year."

Webinar
On Thursday, December 16, 2021, at 2:30 p.m. EST, Mustang will host a webinar with Dr. Shadman and colleague Brian Till, M.D., both of Fred Hutch and physicians at Seattle Cancer Care Alliance, to discuss the updated results from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted CAR T therapy for B-NHLs and CLL. Mustang’s management team will also provide more details on the planned MB-106 Phase 1/2 clinical trial to be conducted under Mustang’s Investigational New Drug ("IND") application. The U.S. Food and Drug Administration ("FDA") has accepted Mustang’s IND to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHLs and CLL. Following the formal presentations, the Mustang team, along with Drs. Till and Shadman, will be available for questions. To register for the webinar, please click here. An archived replay will be accessible on the Events page of the Investor Relations section of Mustang’s website: www.mustangbio.com for approximately 30 days following the call.

About MB-106 (CD20-targeted CAR T Cell Therapy)
CD20 is a membrane-embedded surface molecule which plays a role in the differentiation of B-cells into plasma cells. The CAR T was developed by Mustang’s research collaborator, Fred Hutch, in the laboratories of the late Oliver Press, M.D., Ph.D., and Brian Till, M.D., Associate Professor in the Clinical Research Division at Fred Hutch, and exclusively licensed to Mustang in 2017. MB-106 has been optimized as a third-generation CAR derived from a fully human antibody and is currently in a Phase 1/2 open-label, dose-escalation trial at Fred Hutch in patients with B-NHLs and CLL. Additional information on the trial can be found at View Source using the identifier NCT03277729.

Note: Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

On December 13, 2021 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported interim results from its Phase 1/2 PRIME clinical trial of P-BCMA-101 for the treatment of relapsed/refractory multiple myeloma (R/R MM) at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Poseida Therapeutics, DEC 13, 2021, View Source [SID1234596958]).

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The results show that P-BCMA-101, a non-viral transposon-based autologous CAR-T, was well tolerated and demonstrated strong anti-tumor activity in advanced, late line R/R MM patients. The learnings from P-BCMA-101 informed the development of the Company’s first allogeneic program, P-BCMA-ALLO1 which is also being evaluated in R/R MM patients. The Company previously announced that it is winding down the P-BCMA-101 autologous program in favor of the allogeneic program, P-BCMA-ALLO1.

"We are encouraged by the outcomes seen from our clinical trial of P-BCMA-101, results that continue to validate our approach and that have informed P-BCMA-ALLO1, our first fully allogeneic CAR-T program for patients with multiple myeloma, as well as our other programs. Our focus is on creating differentiated product candidates with a high percentage of T stem cell memory (Tscm) cells," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida Therapeutics. "Looking ahead, we continue to advance P-BCMA-ALLO1 and P-MUC1C-ALLO1 and look forward to presenting data in 2022 for both of these allogeneic programs."

The PRIME trial is a Phase 1/2, open label 3+3 single dose escalation of P-BCMA-101 CAR-T cells. The primary objective of the study is to determine the safety and maximum tolerated dose of P-BCMA-101 based on dose limiting toxicities (DLT), and the key secondary objective is to assess the anti-myeloma effect of the product. The median patient age was 62, with a median time since diagnosis of approximately 5.8 years. Patients were heavily pre-treated, with a median of 7 prior lines of therapy (2-18). As of the data cut-off date of October 15, 2021, a total of 98 patients have been dosed with P-BCMA-101.

The best observed treatment regimen was a combination with rituximab (n=14), with an overall response rate (ORR) of 78%, a VGPR/sCR rate of 43% and 100% overall survival at the time of the data cutoff. Progression free survival was also improved with rituximab, with median overall survival rates not yet reached in several cohorts including the rituximab combination cohorts. Response rates for other cohorts are consistent with results previously reported.

Across the study, no dose-limiting toxicities were observed. 28% of patients developed cytokine release syndrome (CRS) and 7% of patients developed neurotoxicity. None of the patients developed Grade 3 or higher CRS, and 2% of patients developed Grade 3 neurotoxicity. There were no treatment-related deaths among the patient population and no patients needed ICU admission as a result of CAR-T related toxicities. 28 patients were treated on a fully outpatient basis.

"P-BCMA-101 demonstrated strong anti-tumor activity in advanced multiple myeloma patients, and cohorts to date have shown minimal CRS and neurotoxicity, which allows for safe administration in an outpatient environment and combinations with other therapies," said Caitlin Costello, M.D., Associate Clinical Professor of Medicine and member of the Division of Blood and Marrow Transplantation at the University of California, San Diego. "These data indicate that the piggyBac transposon-based platform is an attractive option for allogeneic CAR-T cells, which has led to a first-in-human Phase 1 study."

The Company’s first fully allogeneic CAR-T cell product, P-BCMA-ALLO1 utilizes Poseida’s proprietary piggyBac DNA delivery system and Cas-CLOVER site-specific gene editing system to create an allogeneic product that prevents both graft-vs-host and host-vs-graft diseases and also incorporates a next-generation BCMA binder. P-BCMA-ALLO1 manufacturing involves a proprietary "booster" molecule that allows for numerous doses to be produced from a single manufacturing run, while maintaining desirable Tscm cells, which can reach percentages in the 60-80% range.

The Investigational New Drug (IND) application for P-BCMA-ALLO1 was given a safe to proceed designation by the FDA in August 2021. The Phase 1 study is an open label, dose escalation study following a 3+3 design of dose escalation in subjects with R/R MM. The study will assess the safety and maximum tolerated dose of P-BCMA-ALLO1 based on dose limiting toxicities. Key secondary objectives of the study include the anti-myeloma effect and safety of P-BCMA-ALLO1.

On December 13, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs reported that positive data from the fully enrolled pivotal Phase 3 SIERRA trial of Iomab-B was presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH) (Free ASH Whitepaper) that is being held December 11 – 14, 2021 in Atlanta, Georgia and virtually (Press release, Actinium Pharmaceuticals, DEC 13, 2021, View Source [SID1234596955]). Iomab-B is an antibody radiation conjugate (ARC) targeting CD45 with the Iodine-131 radioisotope payload that is intended to be a targeted conditioning regimen to enable patients to access a bone marrow transplant (BMT). The pivotal Phase 3 SIERRA trial is the only randomized Phase 3 trial for patients age 55 and above with active, relapsed or refractory acute myeloid leukemia (r/r AML) where BMT, the only potentially curative treatment option for this patient population, is feasible. SIERRA is a randomized trial that will compare outcomes of patients receiving Iomab-B and a BMT to those of patients on the control arm receiving physician’s choice of salvage therapy including recently approved targeted agents venetoclax (Bcl-2), midostaurin and giltiritinib (FLT-3), and ivosidenib (IDH) who can potentially receive a BMT if they achieve a remission.

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BMT Engraftment Rates in Evaluable Patients Throughout the SIERRA Trial

BMT Engraftment

25% enrollment
(n=38)

50% enrollment
(n=76)

75% enrollment
(n=113)

100% enrollment
(n=151)

SIERRA

100%

100%

100%

100%*

Conventional
Care

21%

18%

17.5%

17%

Iomab-B
Crossover

100%

100%

100%

100%

• Does not include data from 6 Iomab-B patients for which BMT engraftment and 100-day non-relapse transplant mortality data is still maturing

Dr. Avinash Desai, Actinium’s Chief Medical Officer, said, "The remarkably consistent and high rates of BMT engraftment together with the low rates of non-relapse transplant related mortality at day 100 with Iomab-B through 100% enrollment give us great confidence in SIERRA. Despite 9 AML therapies approved since 2017, many of which are targeted, outcomes for relapsed or refractory patients remain dismal and potentially curative bone marrow transplant is rarely accessible, especially for older patients with active disease like those in SIERRA. This is supported by the fact that only 17% of patients were able to go to transplant in the control arm, which included many of the newly approved targeted therapies. We are highly encouraged that the separation in the number of patients potentially evaluable for the primary endpoint of six-month durable complete remission has remained at approximately 5-times or greater through all data analyses and now at full enrollment."

Grade > 3 Adverse Events

Adverse Event

Iomab-B (n=75)

N (%)

Control Arm (n=76)

N (%)

Sepsis p=0.002

4 (5.3%)

18 (23.7%)

Febrile neutropenia

25 (33.3%)

34 (44.7%)

SIERRA Patient Demographics Through 100% Enrollment

Patients in the Iomab-B arm were a median age of 64 (range: 55-77) and had a median blast count of 30% (range: 2-97) while patients in the control arm were a median age of 65.5 (range: 55-76) and had a median blast count of 20% (range: 3-97)
Over 60% of patients in SIERRA had adverse cytogenetics and over 32% had intermediate risk cytogenetics
Over 50% of patients were primary induction failures, approximately 25% had early relapse (less than 6 months) and the remaining patients were relapsed or refractory or second relapse
66% of patients enrolled in SIERRA received and failed targeted therapies with 66% of patients receiving venetoclax (Bcl-2) based treatment
47% of patients randomized to the control arm in SIERRA received targeted therapies with 81% of patients receiving Venetoclax-based treatment
Dr. Desai continued, "Given the advanced age, high-risk cytogenetic profile, poor disease status and florid active disease of the SIERRA patient population, it is remarkable that Iomab-B has enabled BMT engraftment in 100% of all evaluable patients receiving a therapeutic dose. We are also highly encouraged by the safety and tolerability profile of Iomab-B, which we believe is the result of its targeted nature. We have shown that Iomab-B can deliver high amounts of radiation to the bone marrow but spare vital organs such as the GI tract. We believe this has resulted in the significantly lower rate of sepsis in the Iomab-b arm compared to the control arm, which is a leading cause of transplant related mortality. In addition, lower rates of other adverse events – such as febrile neutropenia combined with the lower rates of 100-day non-relapse transplant related mortality – in the SIERRA arm is exciting. With the final Iomab-B patient receiving their BMT in November 2021, we can confirm our expectation for topline data in the third quarter of 2022. We look forward to presenting additional BMT engraftment, safety and 100-day non-relapse transplant related mortality data from the fully matured data set at a medical conference in early February."

Sandesh Seth, Actinium’s Chairman and CEO, added, "Data from the SIERRA trial have continuously validated our enthusiasm for Iomab-B and its potential to improve patient outcomes. We are struck by not only the consistency of the universal BMT engraftment rates at 25%, 50%, 75% and now 100% enrollment but also the consistency of the SIERRA data with the multiple studies conducted at the Fred Hutchinson Cancer Research Center, which drove our decision to license Iomab-B. As data from the SIERRA trial evolved, the vision to drive a paradigm shift in BMT conditioning, which currently relies on decades old, non-targeted chemotherapy-based regimens that limit access and hinder outcomes, by bringing Iomab-B forward as a targeted conditioning regimen became clear. It is an incredibly exciting time for Actinium to have completed SIERRA trial enrollment and to be on the cusp of producing data to support a BLA filing with the FDA and potential approval. If approved, we will be in a position to execute our vision of leading the paradigm shift to make targeted conditioning for BMT a reality."

The ASH (Free ASH Whitepaper) SIERRA presentation can be accessed on Actinium’s investor relations page View Source

About the SIERRA Phase 3 Trial

The SIERRA trial is a 150-patient, randomized clinical trial, studying Iomab-B compared to the control arm of physician’s choice of salvage therapy in patients with active, relapsed or refractory acute myeloid leukemia (r/r AML) age 55 and above. In SIERRA, patients receiving Iomab-B, those achieving a remission after salvage therapy or those patients not achieving remission after salvage therapy that crossed over to receive Iomab-B were offered a bone marrow transplant (BMT), which is the only treatment option with curative potential for patients with active r/r AML. The SIERRA trial is the only randomized Phase 3 trial intended to offer BMT to this patient population. The control arm of SIERRA included over 20 single agents or combination treatment options based on physician’s choice which include salvage chemotherapy and recently approved targeted agents including Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2 inhibitors as there is no standard of care for this patient population. The SIERRA trial was conducted at 24 sites in the United States and Canada.

About Iomab-B

Iomab-B (I-131 apamistamab) via the monoclonal antibody apamistamab, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, immune cells and bone marrow stem cells. Apamistamab is linked to the radioisotope iodine-131 (I-131) and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient’s cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B may avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer (induction) and marrow cells (myeloablation) including those in bone marrow niches due to the "crossfire" effect enabled by the I-131 radioisotope.

Iomab-B was licensed from the Fred Hutchinson Cancer Research Center where it was studied in nearly 300 patients, in multiple clinical trials in 6 blood cancer indications. Iomab-B is being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are age 55 and above. The SIERRA trial was conducted at 24 preeminent transplant centers in the U.S. and Canada. The primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on Iomab-B and the Phase 3 SIERRA clinical trial can be found at www.sierratrial.com.

On December 13, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that further progress on obecabtagene autoleucel (obe-cel) in an oral presentation [Abstract 477] entitled "Industrialization of an Academic Miltenyi Prodigy-Based CAR T Process" at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held between December 11-14, 2021 (Press release, Autolus, DEC 13, 2021, View Source [SID1234596952]). The Company also presented an update of obe-cel in relapsed/refractory aggressive and indolent B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL) patients from the ALLCAR19 extension study, as well as preclinical and initial engraftment data with AUTO1/22 in Pediatric ALL in two separate poster presentations [Abstracts 3823 and 1710, respectively].

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"We continue to observe sustained responses with obe-cel, with an EFS of 46% at 24 months and patients approaching up to 42 months of durability in the ALLCAR-19 study, supporting the curative potential of obe-cel as a standalone therapy in r/r B-ALL patients. Furthermore, we were encouraged to observe comparable safety and high complete response data between patients treated in the academic ALLCAR19 study and those in the Phase 1b portion of the Autolus sponsored FELIX study," said Dr. Christian Itin, chief executive officer of Autolus. "In addition, we are excited to observe further positive data for obe-cel in r/r B-NHL and B-CLL patients, as well as compelling initial data for AUTO1/22, pointing to the potential for indication expansion and life cycle management opportunities longer term."

Obe-cel in Adult Acute Lymphoblastic Leukemia patients (FELIX study)
Oral Presentation Title: Industrialization of an Academic Miltenyi Prodigy-Based CAR T process
Session Name: 711. Cell Collection and Processing: Advances in Mobilization, Collection, Manipulation and Engineering of HSCs and T Cells
Abstract: #477
Date: Sunday, December 12, 2021
Session Time: 12:00 PM – 1:30 PM ET; Presentation Time: 12:30 PM ET
Location: Georgia World Congress Center, Hall A1
Presenter: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

Initial experience in the phase 1b portion of the FELIX 1b/2 study (NCT04404660) resulted comparable results as seen in the Phase 1 ALLCAR19 study. As of the cut-off date of 13 September, 16 patients in the Phase 1b part of the FELIX study had received obe-cel. Patient characteristics in the FELIX 1b portion were broadly comparable to those observed in the ALLCAR19 study in r/r adult B-ALL.

As of the data cut off date of 15 October 2021, ALLCAR19 data shows morphological EFS for obe-cel is 46% at 24 months with a median follow-up of 29.3 months and patients approaching up to 42 months of durability.
Baseline characteristics between FELIX Phase 1b and ALLCAR19 studies are similar. 75% patients in the FELIX Phase 1b had >20% blasts at pre-conditioning, compared with 60% patients in ALLCAR19. 56.3% patients received prior blinatumomab in the FELIX Phase 1b study compared with 25% in ALLCAR191.
High level of CR/CRi response rate at 1 month observed across both studies, with 12/16 patients in the FELIX Phase 1b study, consistent with 17/201 patients in the ALLCAR19 study.
Safety consistent between the ALLCAR19 study and FELIX Phase 1b study, with no patient having high grade (≥Grade 3) cytokine release syndrome (CRS). 1 of 16 patients experienced a Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) in the FELIX Phase 1b study, as compared with 3 of 20 patients in ALLCAR-19 study1.
The company expects to present data from the Phase 2 portion of the FELIX study in 2022.

1 Roddie et al. "Durable responses and low toxicity after fast off-rate CD19 CAR-T therapy in adults with relapsed/ refractory B-ALL." DOI: 10.1200/JCO.21.00917 Journal of Clinical Oncology – published online before print August 31, 2021

Obe-cel (AUTO1) in Adult Acute Lymphoblastic Leukemia patients (ALLCAR study)
Poster Presentation Title: Safety and Efficacy of AUTO1, a Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)
Session Title: 704. Cellular Immunotherapies: Clinical: Poster III
Abstract: #3823
Date: Monday, December 13, 2021
Presentation Time: 6:00 PM – 8:00 PM ET
Location: Georgia World Congress Center, Hall B5
Presenter: Dr. Claire Roddie, MD, PhD, FRCPath, Consultant Haematologist and Honorary Senior Lecturer, Cancer Institute, University College London (UCL)

As of the data cut-off date of October 15, 2021, 15 r/r B-NHL and 1 B-CLL patient had received obe-cel with 14 patients evaluable for response.

14 of 14 patients responded to obe-cel of which 13 of 14 patients achieved complete metabolic response per Lugano 2014, with 1 B-CLL patient in PR.
15 of 16 patients were without disease progression at last follow-up, with 1 of 16 patients having died in CR from COVID-19. Furthermore, long term persistence was demonstrated by qPCR.
Median follow up time for Follicular Lymphoma (FL) and DLBCL patients was 11.8 months (range 2-14.2m).
Median follow up time for Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma patients was 7.4 months (range 1.1-14.8m).
Across all patients, obe-cel demonstrated a favorable safety profile with no ICANS or severe Grade ≥ 3 CRS events.
The company expects to present further data from more B-NHL and CLL patients in H1 2022.

AUTO1/22 in Pediatric Acute Lymphoblastic Leukemia patients (CARPALL)
Poster Presentation Title: A high sensitivity aCD22 CAR combined with aCD19 CAR to generate dual targeting CAR T cells for the treatment of r/r B-ALL
Session Title: 703. Cellular Immunotherapies: Basic and Translational: Poster I
Abstract: #1710
Date: Saturday, December 11, 2021
Presentation Time: 5:30 PM – 7:30 PM ET
Location: Georgia World Congress Center, Hall B5
Presenter: Dr. Sara Ghorashian, MD, PhD, Hon clinical senior lecturer, UCL Great Ormond Street Institute of Child Health

Obe-cel had previously been tested in r/r pediatric B-ALL2 in the CARPALL Study. Whilst obe-cel was safe and effective, similar to other studies in pediatric B-ALL, antigen escape was a common cause of treatment failure. AUTO1/22 has been designed to address antigen escape by the co-expression of a CD22 CAR with the CD19 CAR in obe-cel. Pre-clinical data demonstrated a high level of in vitro and in vivo activity of AUTO1/22 against leukemia cells. AUTO1/22 was shown to control leukemia in a mouse model of CD19 negative escape. AUTO1/22 is currently being tested in a study of r/r pediatric B-ALL. As of the cut-off date of October 21, 2021, 6 patients had received AUTO1/22. All patients showed engraftment of single and double CAR positive populations, pointing to early CAR T cell persistence. We expect to present clinical data from the full cohort of patients in H1 2022.

2 Ghorashian et al. "Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR." Nature Medicine volume 25, pages1408–1414(2019) (Sept 25, 2019)

Investor call details
Management will host a conference call and webcast on Monday, December 13, 2021 at 8:00 am ET/1:00 pm GMT to discuss the ASH (Free ASH 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 9036269. 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 9036269.