On December 9, 2023 Daiichi Sankyo reported Results from the VALENTINE-PTCL01 phase 2 trial of Daiichi Sankyo’s (TSE: 4568) EZHARMIA (valemetostat tosilate) showed clinically meaningful and durable responses in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) (Press release, Daiichi Sankyo, DEC 9, 2023, View Source [SID1234638341]). The data were presented today in an oral session (#302) at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) (#ASH23) Annual Meeting. PTCL is a group of rare and aggressive blood cancers, which represent about 10 to 15% of all non-Hodgkin lymphomas (NHL).1 A majority of patients with PTCL experience disease progression following initial treatment with a multi-drug chemotherapy-based regimen and median overall survival following relapse is approximately 5.8 months.

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An objective response rate (ORR) of 43.7% (95% CI: 34.6-53.1) was observed with EZHARMIA in 119 patients with relapsed or refractory PTCL as assessed by CT-based blinded independent central review (BICR). Seventeen complete responses (CRs) and 35 partial responses (PRs) were seen. Median duration of response (DoR) of 11.9 months (95% CI: 7.8-NE) was observed after a median follow-up of 9.7 months. Responses were observed across all PTCL subtypes. Median progression-free survival (PFS) of 5.5 months (95% CI: 3.5-8.3) was seen after a median followup of 11.3 months (95% CI: 11.1-13.8) and median overall survival (OS) of 17.0 months (95% CI: 13.5-NE) was observed after a median follow-up time of 12.3 months. An exploratory analysis evaluating responses using PET-CT-based BICR assessment showed an ORR of 52.1% (n=62; 95% CI: 42.8-61.3) with 32 complete metabolic responses (CMRs).

"The high response rates and durability of responses observed with valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma are very encouraging," said Steven M. Horwitz, MD, Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York. "Relapse is too frequent in PTCL and there is an acute need for new medicines beyond standard chemotherapy to better control the disease in the relapsed or refractory setting and improve patient outcomes." The safety profile of EZHARMIA in VALENTINE-PTCL01 (n=133) was consistent with previous clinical trials. Grade 3 or higher treatment emergent adverse events (TEAEs) occurred in 57.9% of patients. The most common grade 3 or higher TEAEs occurring in ≥ 10% of patients were thrombocytopenia (23.3%), anemia (18.8%) and neutropenia (17.3%).

"The results of VALENTINE-PTCL01 support the potential of EZHARMIA as a novel single agent therapy across subtypes of previously treated peripheral T-cell lymphomas," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo.

"The response rate reported and duration of response of nearly one year seen in the study is impressive for this historically difficult-to-treat blood cancer with limited available treatment options." Patients with PTCL enrolled in the study had received a median of two prior treatments (range, 1-12) and 35 patients (26.3%) received prior hematopoietic cell transplant (HCT). At the time of data cut-off of May 5, 2023, 32 patients (24.1%) remained on treatment.

Summary of VALENTINE-PTCL01

Results Efficacy Measure 1 All Patients2 (n=119) ORR (%) (95% CI) CT-based BICR 43.7% (34.6–53.1) CR3 14.3% PR 29.4% Median DoR, months (95% CI) CT-based BICR 11.9 months (7.8-NE) ORR (%) (95% CI) PET-CT-based BICR 52.1% (42.8-61.3) CMR 26.9% Median PFS, months (95% CI) CT-based BICR 5.5 months (3.5-8.3) Median OS (95% CI) 17.0 months (13.5-NE) CR, complete response; CMR, complete metabolic response; DoR, duration of response; NE, not evaluable; ORR, objective response rate; PFS, progression-free survival; PR, partial response; OS, overall survival 1 Efficacy endpoints were evaluated based on Lugano 2014 response criteria 2 Includes PTCL subtypes angioimmunoblastic T-cell lymphoma (AITL), PTCL not otherwise specified (PTCL-NOS), T-peripheral helper (PTCL-TFH), anaplastic large cell lymphoma (ALCL) and "other" PTCL 3 Eight patients with a CR and 10 patients in total proceeded to HCT

About VALENTINE-PTCL01 Trial

VALENTINE-PTCL01 is a global, open-label, single-arm, two-cohort phase 2 study evaluating the efficacy and safety of EZHARMIA in patients with relapsed or refractory PTCL and adult T-cell leukemia/ lymphoma (ATLL) who received at least one systemic therapy and are ineligible for HCT at the time of screening. One cohort enrolled patients with PTCL and a second cohort enrolled patients with ATLL. The primary endpoint of VALENTINE-PTCL01 is ORR based on CT-assessed BICR. Secondary endpoints include DoR, CR, PR, duration of CR and PFS – all assessed by both BICR and investigator assessment – as well as ORR assessed by investigator, OS, safety and pharmacokinetics. Exploratory endpoints include PET-CT-based BICR and biomarker mutational status. Patients were enrolled at approximately 60 sites in Asia, Europe, North America and Oceania. For more information about this study, visit ClinicalTrials.gov.

About Peripheral T-Cell Lymphoma

PTCL is a group of rare and aggressive blood cancers, which represent 10 to 15% of all NHLs. Approximately 544,000 new cases of NHL were diagnosed worldwide in 2020.2 There are at least 29 recognized subtypes of PTCL, which occur with significant geographic variation.3 PTCL is more frequent in Asia compared to Western countries. Prognosis of PTCL is generally poor, with a five-year overall survival rate of 32% in PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) and 7% or lower in certain subtypes. 4 A majority of patients with PTCL experience disease progression after standard first line treatment with a multi-drug chemotherapy-based regimen, at which time treatment options are very limited and median overall survival is 5.8 months.1 Development of more effective medicines for PTCL continues to be an unmet clinical need, particularly in the relapsed or refractory setting.

About EZH1 and EZH2

The EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes help regulate the expression of genes involved in maintaining healthy hematopoietic stem cells (immature blood cells). Both enzymes are recurrently mutated or overexpressed in hematologic malignancies, including T-cell lymphomas, and research shows they contribute to the silencing of tumor suppressor genes and drive oncogenic growth.6,7 About EZHARMIA EZHARMIA (valemetostat tosilate) is a first-in-class dual inhibitor of EZH1 and EZH2 and one of two medicines in the hematology portfolio of Daiichi Sankyo. EZHARMIA is approved in Japan for the treatment of patients with relapsed or refractory ATLL. It is an investigational medicine in all countries outside of Japan.

EZHARMIA Clinical Development Program

In addition to VALENTINE-PTCL01, the EZHARMIA development program includes the pivotal phase 2 trial in relapsed or refractory ATLL in Japan and the phase 1 study in relapsed or refractory NHL in North America and Asia. VALYM, a phase 2 trial in patients with relapsed or refractory B-cell lymphomas, is being conducted under a strategic research collaboration with the LYSA-LYSARC-CALYM group in Europe. EZHARMIA has received SAKIGAKE Designation for the treatment of adult patients with relapsed or refractory PTCL by the Japan Ministry of Health, Labour and Welfare (MHLW).

On December 9, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported two oral presentations and two poster presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 9-12, 2023, including an oral presentation highlighting data from a pooled analysis of the FELIX Phase Ib/II study of obe-cel, an autologous fast off-rate CD19 CAR T therapy, in relapsed/refractory adult B-ALL; and as a poster presentation a long-term update on the pooled ALLCAR19 and FELIX phase 1b studies, evaluating obe-cel in adult patients with r/r B-ALL as well from the ALLCAR19 study patients with B-NHL and B-CLL (Press release, Autolus, DEC 9, 2023, View Source [SID1234638340]). Finally, in an oral presentation pre-clinical and Phase I clinical data from AUTO8, a BCMA/CD19 co-targeting CAR T cell candidate, evaluated in patients with refractory multiple myeloma.

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"The FELIX study, with 127 patients, is one of the largest CAR T cell studies in adults with r/r B-ALL. Obe-cel had a favorable safety profile with very low rates of severe CRS and ICANS, in a clinical setting where these toxicities tend to be frequent and severe. A high proportion of patients responded, with many responses sustained, particularly in patients with low or intermediate disease-burden at lymphodepletion. The FELIX study shows that obe-cel has the potential to become an important therapeutic option in adults with r/r B-ALL," said Dr. Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL).

"The data we are sharing at ASH (Free ASH Whitepaper) from our prior studies indicate that a subset of relapsed and refractory adult ALL patients treated with obe-cel as a single agent continue in remission with a median follow-up of more than three years. It is gratifying to see the excellent safety profile, high response rate and event-free survival we observed in our prior studies, reproduced in the FELIX study," said Dr. Christian Itin, Chief Executive Officer of Autolus. "We have recently submitted a Biologics License Application (BLA) for obe-cel to the U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed/refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (ALL) and we look forward to working with the FDA through the regulatory approval process."

Abstract #222 – oral presentation:

Title: Obecabtagene Autoleucel (obe-cel, AUTO1) for Relapsed/Refractory Adult B-cell Acute Lymphoblastic Leukemia (R/R B-ALL): Pooled Analysis of the Ongoing FELIX Phase Ib/II Study
Link to Presentation
Session Title: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Expanding Disease Targets for CAR-T Cell Therapies
Session date and time: Saturday, December 9, 2023, 3:15 PM PT
Session room: San Diego Convention Center, Room 6B
Publication Number: 222
Presenting Author: Dr. Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL)

Summary:
Obe-cel is an autologous chimeric antigen receptor T cell product using a fast off-rate CD19 binding domain designed to reduce toxicity and increase long-term persistence. A pooled analysis of data from all patients across all cohorts in the FELIX Phase Ib/II study (morphologic disease, minimal residual disease (MRD), isolated extramedullary disease (EMD)) were presented (n=127, median follow-up time from first obe-cel infusion to data cut-off of 16.6 months). Median vein-to-release time was 22 days. Across all patients, treatment with obe-cel resulted in a high response rate with CR/CRi rate of 78% in evaluable patients. Additionally, obe-cel showed a favorable safety profile; grade ≥3 CRS was 2% and grade ≥3 ICANS was 7%, with most severe cases of immunotoxicity occurring in patients with high leukemic burden in the bone marrow (BM). The event free survival estimate (EFS) at 12-months was 50% across all patients, with only 17% of responders proceeding to stem cell transplant while in remission. For patients who had morphologic disease, defined as ≥5% BM blasts or presence of EMD regardless of BM blast status, at lymphodepletion, 74% responded with CR or CRi, and 95% of evaluated responders were MRD-negative‡. For patients who did not have morphologic disease at lymphodepletion, 100% were MRD-negative§ after obe-cel infusion. Subgroup analysis demonstrated that EFS and safety, particularly rate of CRS and ICANS, were better in patients with lower disease burden at lymphodepletion (see table below). Cellular kinetic data shows high expansion and long-term persistence of CAR T cells in most responders.

Table: Summary EFS and safety by bone-marrow blasts prior to lymphodepletion

Overall
(n=127) <5% BM blasts​
(n = 36)​ 5−75% BM blasts​
(n = 51) ​​ >75% BM blasts​
(n = 40)
12-month EFS 50% 65% 55% 27%
≥G3 CRS 2% 0% 4% 3%
≥G3 ICANS 7% 0% 6% 15%
Event free survival (EFS; the time from date of first infusion to the earliest of treatment failure, relapse, or death from any cause); measurable residual disease (MRD); Bone marrow (BM); Extramedullary disease (EMD); complete remission (CR); Complete remission with incomplete count recovery (CRi); ‡ MRD status available for 64/73 patients; § MRD status available for 27/29 patients.

Abstract #350 – oral presentation
Title: Development of a Phase I Study Evaluating the Activity of Modular CAR T for Multiple Myeloma (MCARTY) Targeting BCMA and CD19 for Improved Persistence
Link to Presentation
Session Title: 703. Cellular Immunotherapies: Basic and Translational: Cellular Immunotherapy: Preclinical and Translational Insights
Date and time: Saturday, December 9, 2023, 4:15 PM PT
Session room: San Diego Convention Center, Room 6A
Publication Number: 350
Presenting Author: Dr. Lydia Lee, Consultant Haematologist & Senior Clinical Research Fellow, University College London, Research Department of Haematology (UCLH).

Summary:
AUTO8 is a dual targeting autologous CAR T therapy targeting BCMA and CD19 using two independently expressed CARs (D8 BCMA CAR and AUTO1/obe-cel CAR respectively) for R/R multiple myeloma. The MCARTY study is an iterative, staggered design trial with two separate parallel cohorts for direct comparison of D8 BCMA CAR and AUTO8. As of November 13, 2023 (data cut-off), 11 patients have been infused with either BCMA CAR at 50 million (n=3) or 150 million (n=3) cells, or AUTO8 at 50 million (n=3) or 150 million (n=2). At a median follow-up of 6 months we observed 100% response rate (ORR), with 3 PR, 1 VGPR, 7 CR/sCR (all evaluable MRD negative). Two patients remained in ongoing sCR > 12 months. No cases of ICANS or CRS ≥ Gr 3 were observed across all subjects during the period. While persistence data from the dual targeting cohort is immature, it demonstrates expansion of three CAR populations and suggests a trend to increased persistence of D8 BCMA CAR expressing T cells. The MCARTY trial is ongoing and continues to recruit patients.

Poster Presentations:

Title: Long-Term Efficacy and Safety of Obecabtagene Autoleucel (obe-cel) in Adult Patients (pts) with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia ([R/R B-ALL]; Pooled Analysis from ALLCAR19 and FELIX Phase Ib Studies) or Other B-cell Malignancies (ALLCAR19 Extension Study)
Link to Poster
Session Title: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster Session date and time: Saturday, December 9, 2023, 5:30 PM – 7:30 PM PT
Session room: San Diego Convention Center, Halls G-H
Publication Number: 2114
Presenting Author: Dr. Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL)

Summary:
The clinical activity of obe-cel has been explored in adults with R/R B-ALL in a Phase I study (ALLCAR19), and a Phase Ib/II study (FELIX). Additionally, obe-cel has been tested in patients with R/R B-cell chronic lymphocytic leukemia (B-CLL) and R/R B-cell non-Hodgkin lymphoma (B-NHL). Data from the pooled analysis of r/r ALL patients (n=36) treated with obe-cel in the ALLCAR19 and FELIX Ib studies demonstrate high remission rates of 81% (29/36). After a median follow-up of 3 years and without subsequent transplant 41% of patients continue in complete remission. The estimated EFS rate with censoring of subsequent transplant or new treatment was 45% at 36 months; all patients in ongoing remission were MRD negative at last assessment and median duration of response was not reached. In the CLL and NHL cohorts of the ALLCAR19 study and with >2 years follow up, high response rates and durable responses were observed. Low grade or low frequency grade >3 CRS/ICANS was observed across all indications and all dosing regimens. Excellent expansion and persistence of CAR T cells was evident across the studies. In summary, obe-cel shows durable remissions in a range of B-cell malignancies with a consistent safety profile.

Title: Delivery of Obecabtagene Autoleucel (obe-cel, AUTO1) for the FELIX Pivotal Study Demonstrating Robust Cell Processing, Robust Release Testing, and Reliable Logistics, Together with Readiness for Sustainable Patient (pt) Care
Session Title: 711. Cell Collection and Processing: Poster III
Session date and time: Monday, December 11, 2023, 6:00 PM – 8:00 PM PT
Session room: San Diego Convention Center, Halls G-H
Publication Number: 4892
Presenting Author: Michael Merges VP, Process Development, Autolus

Analyst/Investor Event:

Date: Sunday, December 10, 2023
Time: The presentation will be from 8:00 AM PT / 4:00 PM GMT to 9:00 AM PT / 5:00 PM GMT. Onsite access to the event available from 7:45 am PT
Venue: The Manchester Grand Hyatt, 1 Market Place, San Diego, CA 92101
Speakers: Dr. Claire Roddie, MD, Ph.D., FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL); Dr. Christian Itin, Chief Executive Officer, Autolus.
Webcast Registration: A live webcast will be held alongside the event. To register for the webcast please follow this link.

A recording of the event together with the presentation materials will be available on the Company’s website after the event.

Note that due to the ASH (Free ASH Whitepaper) embargo policy details specific to Publication 4892 will not be included in the Analyst/Investor event.

On December 9, 2023 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, reported that a growing body of clinical data for Aptose’s lead compound tuspetinib (TUS), demonstrates significant benefit as a single agent and in combination with venetoclax (VEN) in patients with relapsed or refractory acute myeloid leukemia (R/R AML) in the ongoing APTIVATE Phase 1/2 study (Press release, Aptose Biosciences, DEC 9, 2023, View Source [SID1234638339]). Data were presented in an oral presentation today at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition by lead investigator Naval G. Daver, M.D., Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.

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Tuspetinib is a once-daily, oral, precision targeted kinase inhibitor that suppresses select kinases that drive the proliferation of AML. These key kinase targets include the SYK, FLT3, JAK1/2, mutant forms of KIT, RSK2, and the TAK1-TAB1 kinases operative in AML, while avoiding non-therapeutic kinase targets to promote safety.

Dr. Daver reported data from more than 100 relapsed/refractory patients from multiple international clinical sites, who had failed prior therapy and then were treated with tuspetinib (TUS) as a single agent or tuspetinib in combination with venetoclax (TUS/VEN). TUS and TUS/VEN delivered multiple composite complete remissions (CRcs) in this very ill AML population, while maintaining a favorable safety profile across all treated patients.

"Tuspetinib is clearly an active and surprisingly well tolerated agent in one of the most challenging and heterogeneous disease settings in oncology – relapsed and refractory AML," said Dr. Daver. "Tuspetinib has demonstrated broad activity, including activity in patients with FLT3 wild-type AML (accounting for more than 70% of the AML population), FLT3 mutated AML, NPM1 mutated AML, as well as in patients with mutations historically associated with resistance to targeted therapy. Most notably, TUS targets VEN resistance mechanisms, enabling TUS/VEN uniquely to treat the very ill prior-VEN AML population, including both FLT3 mutant and FLT3 wildtype disease. From a broader perspective, the growing body of antileukemic activity, and continued favorable safety profile, support advancement of tuspetinib in a TUS/VEN/HMA triplet for the treatment of frontline newly diagnosed AML patients."

Dr. Daver also pointed out that while patients on the TUS/VEN therapy are early in their treatment cycles, most achieving a response remained on treatment and that responses have begun to mature as dosing continues.

Highlights of Dr. Daver’s ASH (Free ASH Whitepaper) oral presentation:

TUS as Single Agent

As a single agent at therapeutic doses of 80-160 mg in 68 evaluable patients, TUS was more active in VEN-naïve patients, with an overall CRc rate of 29% (8/28)
This included a 42% CRc rate (5/12) in FLT3-mutated patients
And a 19% CRc rate (3/16) in FLT3-unmutated, or wildtype, AML patients
Responses and blood counts improved with continuous dosing
Many bridged to an allogeneic stem cell transplant (HSCT)
Durability was observed when HSCT was not performed
80 mg was selected as the recommended phase 2 dose
Tuspetinib showed a favorable safety profile with only mild adverse events (AEs) and no dose-limiting toxicities (DLTs) up to 160 mg per day, and no drug discontinuations from drug related toxicity
TUS/VEN Combination Therapy

In the TUS/VEN doublet study, 49 patients were dosed with 80 mg of tuspetinib and 200 mg of venetoclax, with 36 evaluable (and 13 patients too early to assess)
Patients were heavily exposed to Prior-VEN and Prior-FLT3 inhibitor treatment
TUS/VEN was active in both VEN-naïve and prior Prior-VEN relapsed/refractory patients
TUS demonstrated composite complete remission (CRc) rates:
Among all evaluable patients, TUS/VEN demonstrated a CRc rate of 25% (9/36); 43% (3/7) in VEN-naïve patients, and 21% (6/29) in Prior-VEN patients.
Among FLT3 wildtype patients, TUS/VEN demonstrated an overall CRc rate of 20% (5/25); 33% (2/6) in VEN-naïve patients, and 16% (3/19) in Prior-VEN patients
Among FLT3 mutant patients, TUS/VEN demonstrated an overall CRc rate of 36% (4/11); a complete response in a VEN-naïve patient (1/1); a 30% (3/10) in Prior-VEN patients; and 44% (4/9) in patients treated prior with a FLT3 inhibitor
Key findings:
TUS/VEN is a well tolerated combination therapy
TUS/VEN is active across broad populations of R/R AML
TUS/VEN is active in FLT3 wildtype, representing ~70% of AML patients
TUS/VEN retains activity in the difficult-to-treat Prior-VEN AML population
"The wealth of data we have generated – and continue to generate – on tuspetinib points to a highly active, well-differentiated drug for AML populations that are in need of options beyond currently available therapies," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer at Aptose. "Brisk patient enrollment in our APTIVATE trial has led to a fast-growing database that includes many more patients at various stages of treatment. We look forward to reporting our next set of data in the first quarter of 2024."

The slides from Dr. Daver’s presentation are available on Aptose’s website here.

On December 9, 2023 Scenic Biotech, a pioneer in the discovery of genetic modifiers developing therapeutics to treat severe diseases, reported positive preclinical data for its lead small molecule QPCTL inhibitor, SC-2882 (Press release, Scenic Biotech, DEC 9, 2023, View Source [SID1234638335]). The data was also presented today by Leandro Cerchietti, MD, Richard A. Stratton Associate Professor in Hematology and Oncology at Weill Cornell Medicine, New York, at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in San Diego. The new preclinical data covers results for SC-2882, Scenic’s first-in-class QPCTL inhibitor, as a potential new treatment approach for diffuse large B-cell lymphoma (DLBCL). DLBCL accounts for 25-30% of all non-Hodgkin lymphoma cases, making it the most common cancer of the lymphatic system characterized by rapidly growing tumor mass or enlarging lymph nodes in a nodal or extranodal site.

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"Treatment with SC-2882 in a DLBCL mice model achieved a significant decrease in tumor growth and an increase of CD3+ T cell infiltration within the tumor microenvironment, along with a reduction in immunosuppressive immune cells. This suggests that QPCTL inhibition in DLBCL has anti-lymphoma effects and holds potential as a new therapeutic avenue for this type of cancer," commented Leandro Cerchietti, MD, Associate Professor in Hematology and Oncology at Weill Cornell Medicine, New York, and presenter at the 65th ASH (Free ASH Whitepaper) Annual Meeting & Exposition.

"The positive preclinical data presented today constitute a major step forward in the advance of SC-2882 as a potential treatment for DLBCL, an indication with high unmet medical need especially in post-CART relapsed or refractory DLBCL patients, as well as in earlier lines of treatment with non-chemotherapy or immuno-oncology-based approaches. QPCTL was identified as a new immuno-oncology target through our proprietary Cell-Seq platform, and we view these results as a validation for our approach and our earlier-staged Cell-Seq-generated programs in rare diseases," commented

Jens Würthner, MD, PhD, CMO of Scenic Biotech. "As we finalize IND-enabling studies for SC-2882, we look forward to submitting our initial clinical trial filing to the regulatory authorities in 2024 and moving into clinical evaluation."

QPCTL is an intracellular enzyme that modulates the activity of CD47 and several chemokines in cancer leading to immune escape of cancer cells. SC-2882 targets QPCTL and thereby inhibits the CD47-SIRPα "don’t eat me" checkpoint and lowers immune suppression in the tumor microenvironment. Analysis of DLBCL patient datasets revealed that QPCTL expression negatively correlates with overall and progression-free survival. In a murine model of DLBCL, SC-2882 treatment led to a significant decrease in tumor growth with no evidence of systemic toxicity. Moreover, evaluation of the tumor microenvironment (TME) showed an increased CD3+ T cell infiltration and a reduction in tumor-associated macrophages and regulatory T cells in SC-2882-treated mice, compared to control. These results imply SC-2882 exhibits an anti-tumor effect that involves modulation of immunosuppression in the TME.

The data was described today in an oral presentation by Leandro Cerchietti, MD, Richard A. Stratton Associate Professor in Hematology and Oncology at Weill Cornell Medicine, New York, at 9:30 AM PST/ 18:30 CET during session 605 entitled "Molecular Pharmacology and Drug Resistance – Lymphoid Neoplasms: Novel Therapeutic Approaches in Lymphoma and Multiple Myeloma".

On December 9, 2023 Orca Bio, a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer, autoimmune diseases and genetic blood disorders, reported positive new data that suggest its investigational high-precision cell therapies, Orca-T and Orca-Q, have the potential to deliver improved clinical outcomes across different age ranges, donor types and conditioning regimens relative to existing standard of care allogeneic hematopoietic stem cell transplants (alloHSCT) (Press release, Orca Bio, DEC 9, 2023, View Source;utm_medium=rss&utm_campaign=orca-bio-presents-positive-data-demonstrating-the-potential-for-orca-t-and-orca-q-to-expand-treatment-to-additional-patient-groups-at-the-65th-ash-annual-meeting [SID1234638331]). The results presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting showed promising data with the use of Orca Bio’s cell therapies across several patient groups where there is significant unmet medical need.

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Orca-T in Older Patients with Myeloablative Conditioning

Results highlighted in an oral presentation showed Orca-T’s ability to deliver similar outcomes in older patients undergoing myeloablative conditioning (MAC) as younger patients. Notably, Orca-T delivered similar results across disease control, non-relapse mortality (NRM) and overall survival (OS).

"While the use of MAC offers the best chance of a cure, it also increases life-threatening complications in older patients receiving standard of care alloHSCT," said presenting author Caspian Oliai, M.D., medical director of the UCLA Bone Marrow Transplantation Stem Cell Processing Center. "These latest findings suggest a cell therapy like Orca-T, which has the potential to offer a cure while reducing toxicity and lowering treatment-related mortality, may allow older patients to better tolerate MAC. This approach could expand curative treatment to older patients who might not be offered a MAC regimen today, and potentially provide physicians with an important new option in our ongoing efforts to balance the risk of relapse with transplant-related side effects."

In a subgroup analysis, 64 patients from Orca Bio’s ongoing multi-center Phase 1b clinical trial who received Orca-T and busulfan, fludarabine and thiotepa (BFT) conditioning for the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), mixed phenotype leukemia, chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) were divided into two age groups: 18-54 years of age (n=39), and 55 years of age and older (n=25). With a median follow-up of 12 months, the following outcomes were reported:

Relapse-free survival (RFS) was 84.8% in younger patients and 82.3% in older patients.
NRM was 0% in both groups.
OS was 100% and 95.5% in the younger and older patient groups, respectively.
Events of grade 3-4 acute graft versus host disease (GvHD) and moderate-to-severe chronic GvHD were low across the younger group (0 and 3, respectively) and older group (1 and 3, respectively).
Across all patients, Orca-T continued to be manufactured reliably and delivered with vein-to-vein times of 72 hours or less across the U.S.

Orca-T in Older Patients with Reduced Intensity Conditioning

Additional data from a single-center open-label Phase 1 clinical trial presented at ASH (Free ASH Whitepaper) looked at the outcomes of older patients treated with Orca-T and a reduced intensity conditioning (RIC). These patients were found to be unfit for a MAC regimen due to the significant risks associated with it, particularly in older age. At 12 months, patients treated with a RIC Orca-T (n=15) saw no observable compromise in curative outcomes, with no patients experiencing relapse (0%). Patients also saw encouraging RFS (79%) and a low incidence of both grade 3-4 acute and chronic GvHD (0% and 7%, respectively).

Collectively, these findings support the potential for Orca-T to treat older patients with hematological malignancies, whether they are given a MAC or RIC regimen, with no new safety signals reported.

Orca-T in Patients with MDS

New data was also presented on the performance of Orca-T in patients with intermediate to high-risk MDS. Current treatments for MDS aren’t often curative, and many patients relapse or become resistant to first-line treatment. There remains an unmet need for new, more effective but tolerable strategies to manage MDS.

In this subgroup from the ongoing multi-center Phase 1b clinical trial, Orca-T demonstrated promising results in this patient population (n=16). At one year, RFS with Orca-T was 94%. No patients experienced grade 3-4 acute GvHD, and moderate-to-severe chronic GvHD occurred in two patients. The rates of NRM and OS with Orca-T were 0% and 94%, respectively.

Orca-T is currently being evaluated in a pivotal Phase 3 clinical study for the treatment of AML, ALL and MDS at leading transplant centers across the U.S.

Orca-Q for Patients with Haploidentical Donors

In an oral presentation, Orca Bio shared updated data from a multi-center Phase 1 clinical trial of its second high-precision cell therapy, Orca-Q, in patients with a haploidentical donor without the use of post-transplant cyclophosphamide (PTCy).

"Orca-Q is a first-in-class therapy that has the potential to improve patient outcomes and reduce the risk of graft versus host disease without the use of PTCy," said presenting author Samer Srour, M.D., M.S., Department of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center. "While PTCy has increased the use of haploidentical HSCTs, it can bring a myriad of risks and toxicities that we didn’t experience with Orca-Q. These updated results in an expanded group of patients continue to support Orca-Q’s promise to overcome the challenges of haploidentical stem cell transplant by providing a solution where patients and physicians may no longer have to compromise between the risk of relapse and the risk of GvHD."

The positive outcomes from an expanded group of 33 patients with AML, ALL and CML support Orca-Q as a potential treatment option for patients with a haploidentical donor. With a median of 375 days follow-up, updated safety and efficacy data include:

No patients experienced moderate-to-severe chronic GvHD (0%).
There was one event of grade 3 acute GvHD and no grade 4 acute GvHD.
NRM was 9%.
RFS, GRFS and OS at one year were 82%.
Additionally, no new safety signals were identified. The estimated incidence of CTCAE grade 2 and greater than grade 3 infections at one year were 9% and 15%, respectively.

"At Orca Bio, we understand the challenges providers face in achieving the right balance in offering blood cancer patients the best option for a cure with optimal quality of life," said Ivan Dimov, Ph.D., co-founder and chief executive officer of Orca Bio. "We are pleased to present these latest findings at ASH (Free ASH Whitepaper) that add to our growing body of clinical evidence which underscore the potential of our novel high-precision platform to expand potentially life-saving treatment to more patient groups who could benefit."

The full ASH (Free ASH Whitepaper) presentations will be made available on www.orcabio.com.

About Orca-T
Orca-T is an investigational high-precision allogeneic cell therapy being evaluated in clinical trials for the treatment of multiple hematologic malignancies. Orca-T includes infusions containing regulatory T-cells, CD34+ stem cells and conventional T-cells derived from peripheral blood from either related or unrelated matched donors. Orca-T is currently being evaluated in a pivotal Phase 3 clinical trial at leading transplant centers across the U.S. and has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration.

About Orca-Q
Orca-Q is an investigational high-precision allogeneic cell therapy being evaluated in clinical trials for the treatment of hematologic malignancies in patients with haploidentical donors. Orca-Q is a proprietary composition of stem cells combined with specific T-cell subsets derived from healthy donors and engineered by Orca Bio’s high-precision platform. Orca-Q has the potential to improve patient outcomes and reduce the risks of toxicities without the use of post-transplant cyclophosphamide (PTCy) in patients unable to identify a full human leukocyte antigen (HLA) match.