On December 10, 2022 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported data from the safety lead-in portion of its ongoing SELECT-AML-1 Phase 2 trial evaluating tamibarotene, an oral, selective retinoic acid receptor alpha (RARα) agonist, in combination with venetoclax and azacitidine in newly diagnosed, unfit patients with acute myeloid leukemia (AML) and RARA gene overexpression (Press release, Syros Pharmaceuticals, DEC 10, 2022, View Source [SID1234625061]). The data is being presented today in a poster session at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place in New Orleans, LA.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"As a physician devoted to the care and treatment of leukemia, I am reminded daily of the limitations of existing therapeutic options, with approximately one-third of unfit AML patients failing to respond in the frontline setting and nearly all relapsing over time," said Daniel Pollyea, M.D., M.S., Professor of Medicine and Clinical Director of Leukemia Services at the University of Colorado School of Medicine. "These data provide early evidence that tamibarotene can be combined with the existing standard-of-care to deliver improved outcomes to the approximately 30% of AML patients who are positive for RARA overexpression – many of whom present with a disease phenotype associated with features of venetoclax resistance. I look forward to enrolling patients in the randomized portion of the Phase 2 trial and to further characterizing the potential of tamibarotene as a novel combination agent for use in patients with hematologic malignancies."

"We are highly encouraged by the initial data from SELECT-AML-1, which address the two questions we set out to answer in the safety lead-in, demonstrating both the tolerability of tamibarotene in combination with venetoclax and azacitidine, as well as the potential clinical benefit of adding tamibarotene to existing standard-of-care," said David A. Roth, M.D., Chief Medical Officer of Syros. "In AML patients with RARA gene overexpression, the triplet regimen with tamibarotene at full dose demonstrated a high response rate and rapid onset of action, with no evidence of increased toxicities beyond what would be expected with the combination of venetoclax and azacitidine. Based on these data, we intend to move rapidly to initiate the randomized portion of our Phase 2 SELECT-AML-1 trial, while also continuing to enroll patients in SELECT-MDS-1, where we are evaluating the combination of tamibarotene with standard-of-care azacitidine in patients with higher-risk myelodysplastic syndrome and RARA gene overexpression."

Encouraging Initial Data from SELECT-AML-1 Phase 2 Trial
As of October 13, 2022, eight newly diagnosed, unfit, RARA-positive patients had been enrolled in the trial, including six who were evaluable for response. The median age of the patients was 61 (ranging from 55-82) and the median percent blasts at baseline was 63% (ranging from 39-100%).

Initial Safety Data
– Tamibarotene in combination with venetoclax and azacitidine administered at approved doses showed no evidence of increased toxicity relative to the doublet combination of venetoclax and azacitidine. This includes rates of myelosuppression, which were comparable to reports with venetoclax and azacitidine in this population.
– Serious adverse events (SAEs) were reported in all six patients. The most frequently occurring SAEs included febrile neutropenia (66%) and pneumonia (50%).
– The majority of non-hematologic AEs were low grade and reversible. The most frequently occurring non-hematologic AEs included pneumonia (66%), cough (50%), anxiety (50%), decreased appetite (50%) and rash (50%).

Initial Clinical Activity Data
– The complete response (CR) and complete response with incomplete blood count recovery (CRi) rate, as defined by Revised International Working Group (IWG) criteria was 83%, consisting of two patients (33%) who achieved a CR and three patients (50%) who achieved a CRi.
° Four of five patients (80%) who achieved a CR or CRi had a high monocytic expression score (MES), which may be associated with venetoclax resistance.1
– Median time to CR/CRi response was 33 days (ranging from 25-88).
– Median duration of treatment was 76.5 days (ranging from 20-104) and median duration of follow-up was 107 days (ranging from 56-314).
– These early data compare favorably to the standard-of-care combination of venetoclax and azacitidine, which shows composite CR rates of 66% in newly diagnosed unfit AML patients.2

Advancing Tamibarotene in Newly Diagnosed Unfit AML
Based on the encouraging data reported today, Syros plans to advance into the randomized portion of the SELECT-AML-1 Phase 2 trial, which will evaluate the safety and efficacy of tamibarotene in combination with venetoclax and azacitidine in approximately 80 patients positive for RARA overexpression randomized 1:1 to treatment with tamibarotene and venetoclax/azacitidine vs. venetoclax/azacitidine. The trial will incorporate venetoclax dose modification guidelines based on the recently published European LeukemiaNet (ELN) recommendations,3 and will also evaluate the triplet regimen as a salvage therapy in patients who do not respond to venetoclax and azacitidine in the control arm. The randomized portion is expected to initiate in Q1 2023, with data expected in 2023 or 2024.

The ASH (Free ASH Whitepaper) presentation is now available on the Publications and Abstracts section of the Syros website at www.syros.com.

Conference Call Information

Syros will host a conference call at 12:00 p.m. ET today to discuss these data, as well as review the unmet need in newly diagnosed, unfit AML. In addition to Syros management, the event will feature a presentation from Daniel Pollyea, M.D., M.S., Associate Professor of Medicine, Clinical Director of Leukemia Services, University of Colorado School of Medicine. To access the live event, please register here. In addition, a live webcast of the presentation will be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following the presentation.

On December 10, 2022 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer, reported positive safety and efficacy data from the Company’s ongoing Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell NHL (Press release, Adicet Bio, DEC 10, 2022, View Source [SID1234625060]). The Company believes these data continue to support the potential of Adicet’s investigational gamma delta CAR T cell therapy to provide significant benefit both in terms of anti-tumor activity and safety. Based on the study findings as of a December 5, 2022 data-cut date, Adicet plans to transition ADI-001 into a potentially pivotal program in the second quarter of 2023.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"It is very encouraging to see durability of response at six months and beyond along with a continued favorable safety profile in patients with aggressive lymphomas," said Francesco Galimi, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Adicet Bio. "Notably, a 100% complete response rate with ADI-001 in post-autologous CAR T-relapsed LBCL patients may offer a potential treatment option to those patients, who do not currently have effective therapies."

"These data are exciting and support our belief that ADI-001 has the potential to generate meaningful clinical responses for patients," said Chen Schor, President and Chief Executive Officer of Adicet Bio. "Based on the positive data reported today, we plan to transition ADI-001 into a potential pivotal program with a potentially best-in-class ORR, CR and durability profile in the second quarter of 2023."

"As these data mature, it is impressive to see continued complete responses across all dose levels including six-month durable responses and a 100% ORR and CR rate in LBCL patients previously treated with autologous CAR T therapy," said Sattva Neelapu, M.D., Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. "Achieving these results in such high-risk patients with aggressive disease suggests that an allogeneic gamma delta CAR T cell therapy like ADI-001 could provide a significant advance for NHL patients."

Data highlights as of the December 5, 2022 data-cut date were as follows:

Of the 16 evaluable patients, three received ADI-001 at dose level 1 (DL1) (30 million CAR+ cells), three received ADI-001 at DL2 (100 million CAR+ cells), three received ADI-001 at DL3 (300 million CAR+ cells), one received two infusions of ADI-001 at DL3 (2X 300 million CAR+ cells on day one and seven following a single lymphodepletion), and six received ADI-001 at DL4 (1 billion CAR+ cells).
On an exploratory basis, primarily to understand safety and pharmacokinetics of a second ADI-001 dose, the first and second patient in DL3 while testing negative for minimal residual disease (MRD) and in CR, received a second DL3 dose, three and two months after the first infusion, respectively.
Patients were heavily pretreated with a median number of prior therapies of four (range two-six) and had a poor prognostic outlook based on their median International Prognostic Index (IPI) score.
ADI-001 treatment demonstrated a 75% ORR and 69% CR rate in the study across all dose levels.
In five LBCL patients that previously relapsed after prior autologous anti-CD19 CAR T therapy, treatment with ADI-001 demonstrated 100% ORR and CR rate (5/5). These patients included a triple-hit high-grade B-cell lymphoma patient, three diffuse large B-cell lymphoma (DLBCL) patients, and a double-hit high-grade B-cell lymphoma patient. ADI-001 resulted in CR in patients who previously showed a partial response (PR) to autologous CAR T (2/2).
An 86% CR rate (6/7) was observed in LBCL patients across DL3 and above. 75% CR rate (9/12) in LBCL across all dose levels.
Both DL2 and DL3 demonstrated a six-month CR rate of 33%; Patient follow up continues in DL4 to assess six-month durability.
Circulating ADI-001 cells were visible through day 28 in peripheral blood at DL4.
ADI-001 was generally well-tolerated in the study to date. There were no occurrences of dose-limiting toxicities, graft vs host disease (GvHD), or Grade 3 or higher Cytokine Release Syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) reported.
Table 2: Summary of Phase 1 ADI-001 Preliminary Safety Data in Efficacy-Evaluable Patients as of the December 5, 2022 data-cut date:+

DL1 (3E7)​
N=3

DL2 (1E8)​
N=3

DL3 (3E8)​
N=3

DL3 (2X 3E8)
Day 1&7
N=1

DL4 (1E9)​
N=6

Total​
N=16

Adverse
Event
Types

All
Grade​
N (%)

Gr ≥3​
N (%)

All
Grade
N (%)

Gr ≥3​
N (%)

All
Grade
N (%)

​Gr ≥3​
N (%)

All
Grade​
N (%)

Gr ≥3​
N (%)

All
Grade
N (%)

Gr ≥3​
N (%)

All
Grade ​
N (%)

Gr ≥3​
N (%)

CRS

2 (67%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

1 (100%)

0

3 (50%)

0 (0%)

6(38%)

0 (0)

ICANS

0 (0%)

0 (0%)

1 (33%)

0 (0%)

0 (0%)

0 (0%)

0

0

1(17%)

0 (0%)

2(13%)

0 (0)

GvHD

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0

0

0 (0%)

0 (0%)

0 (0)

0 (0)

DLTs

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0 (0%)

0

0

0 (0%)

0 (0%)

0 (0)

0 (0)

Infection

1 (33%)

0 (0%)

0 (0%)

0 (0%)

1 (33%)

1 (33%)

0

0

0 (0%)

0 (0%)

2 (13%)

1 (6%)

SAE –
TEAE

1

(33%)

1

(33%)

2 (67%)

2 (67%)

2

(67%)

2 (67%)

0

0

1

(17%)

0

(0%)

6

(38%)

5

(31%)

+Safety assessment was performed using the Common Terminology Criteria for Adverse Events (v5) and the American Society for Transplantation and Cellular Therapy criteria.

Enrollment in the Phase 1 clinical study of ADI-001 is currently ongoing to provide additional durability data and further support the recommended Phase 2 dose.

The Company expects to discuss with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) a potential path to support a Biologics License Application (BLA) and Marketing Authorization Application (MAA) for ADI-001, including potential pivotal studies in post-CAR-T LBCL patients and in earlier line LBCL patients, respectively.

Webcast / Conference Call information

Adicet will host a webcast presentation on Sunday, December 11, 2022 at 9:00 a.m. EST to discuss the most recent data-cut from its ongoing Phase 1 study evaluating the safety and tolerability of ADI-001 for the potential treatment of relapsed or refractory B-cell NHL. The event will feature Sattva Neelapu, M.D., Professor in the Department of Lymphoma-Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, alongside members of the Adicet management team.

The live webcast of the presentation can be accessed by registering under "Presentations & Events" in the investors section of the Company’s website at View Source Upon registration, all participants will receive a confirmation email with a unique passcode to provide access to the webcast event. To participate via telephone, please join by dialing 1-833-548-0276 (domestic) or 1-646-876-9923 (international) and referencing the conference ID 98173615816.

An archived replay will be available for 30 days following the presentation. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About ADI-001

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent anti-tumor activity in preclinical models, leading to long-term control of tumor growth. In April 2022, ADI-001 was granted Fast Track Designation by the FDA for the potential treatment of relapsed or refractory B-cell NHL.

About the GLEAN Study

This Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to, at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).

On December 10, 2022 Pfizer Inc. (NYSE:PFE) reported 10.4 month follow-up data from the pivotal Phase 2 MagnetisMM-3 clinical trial suggesting elranatamab, a B-cell maturation antigen (BCMA)-CD3-targeted bispecific antibody (BsAb), is efficacious and has a manageable safety profile in patients with relapsed or refractory multiple myeloma (RRMM) in a heavily pretreated population, who have received at least three classes of prior therapies including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody (i.e. triple-class refractory or exposed) (Press release, Pfizer, DEC 10, 2022, View Source [SID1234625059]). These data are being presented today in an oral session at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition 2022 (abstract 159).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Forward-Looking Information and Factors That May Affect Future Results"

Tweet this
"Although there are approved treatments for multiple myeloma, none are currently curative, and patients often find themselves with dwindling therapeutic options as their disease relapses or becomes refractory to successive medicines," said Nizar Bahlis, M.D., Associate Professor, Arnie Charbonneau Cancer Institute, University of Calgary, Canada, and lead investigator. "These longer-term results show early and deep responses with elranatamab in a heavily pretreated patient population, adding to the growing body of evidence showing elranatamab has the potential to be a transformative option in an area of high need."

Elranatamab is an investigational humanized BsAb that targets both BCMA-expressing multiple myeloma cells and CD3-expressing T-cells, bridging them together and activating the T-cells to kill the myeloma cells. The binding affinities of elranatamab for BCMA and CD3 have been engineered to elicit potent T-cell-mediated anti-myeloma activity. Given factors currently limiting the availability of novel therapies in the triple-class exposed setting, elranatamab has the potential to reach a broader and greater number of patients as an off-the-shelf option that is administered subcutaneously (SC), which offers more convenience over intravenous administration.

In this analysis, safety and efficacy were analyzed in 123 patients who had received at least one dose of elranatamab (cohort A – BCMA-naïve) as of the data cut-off on October 14, 2022. Patients received SC elranatamab 76 mg weekly (QW) on a 28-day cycle with a step-up priming dose regimen, 12 mg and 32 mg administered on Day 1 and Day 4, respectively, during Cycle 1. With a median follow up of 10.4 months, patients who received elranatamab achieved a high objective response rate of 61%, with 84% probability of maintaining response at nine months. Probability of progression-free survival and overall survival were 63% and 70%, respectively, at nine months. The results also suggest elranatamab has a manageable safety profile and that the two-step-up priming dose regimen (12/32 mg) mitigated the rate and severity of cytokine release syndrome (CRS) (58%, all Grade 1/2) and immune effector cell-associated neurotoxicity syndrome (ICANS, 3%, all Grade 1/2) in cohort A of MagnetisMM-3 (n=119). The most common hematologic treatment emergent adverse events (TEAEs) of any grade were – anemia (48%), neutropenia (48%), thrombocytopenia (30%) and lymphopenia (26%).

"Discovered and developed at Pfizer, elranatamab is just one example of our focus on investing in breakthrough science. We’re applying our expertise in hematology developed over a decade to advance elranatamab as an innovative treatment for multiple myeloma," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. "We are excited to be sharing our latest research at ASH (Free ASH Whitepaper), which further supports the efficacy and safety of elranatamab, and will continue to evaluate its potential benefits through the MagnetisMM clinical trial program across earlier and broader populations, including newly diagnosed patients. We are excited by the potential for elranatamab, if approved, to reach a greater number of patients globally across the treatment paradigm."

Additional Pfizer elranatamab presentations at ASH (Free ASH Whitepaper) include:

Elranatamab, a BCMA Targeted T-Cell Engaging Bispecific Antibody, Induces Durable Clinical and Molecular Responses for Patients with RRMM (abstract 158, oral)
MagnetisMM-1 Phase 1/2 first in human MagnetisMM-1 study (NCT03269136)
Safety and preliminary efficacy results from Part 1 (safety lead-in cohort) of MagnetisMM-5, a Phase 3 study of elranatamab + daratumumab in patients with RRMM (NCT05020236) (poster 1921)
MagnetisMM-4: An Open Label, Phase 1b/2 Umbrella Study of Elranatamab in Combination with Other Anti-cancer Treatments for Patients with Multiple Myeloma (poster 4567)
Phase 1b/2 MagnetisMM-4 (NCT05090566) ongoing clinical trial
Dose Optimization to Mitigate the Risk of CRS with Elranatamab in Multiple Myeloma (poster 3192)
Dose-optimization analysis from across MagnetisMM-1 (NCT03269136), MagnetisMM-2 (NCT04798586), MagnetisMM-3 (NCT04649359) and MagnetisMM-9 (NCT05014412)
A Systematic Meta-analysis of Cytokine Release Syndrome Incidence in B-Cell Maturation Antigen-Targeting Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies for Patients with Relapsed and/or Refractory Multiple Myeloma (poster 4509)
Meta-analysis of CRS among patients treated with BCMA-targeting CAR-Ts and BsAbs across 53 studies
MagnetisMM-3 (NCT04649359) is an ongoing open-label, multicenter, non-randomized study designed to evaluate the safety and efficacy of elranatamab as monotherapy in patients with RRMM. Additional data continue to be collected and will be shared as they mature. Prior to enrollment, participants had received a median of five lines of treatment. The participants included in this study represent a difficult-to-treat multiple myeloma patient population; almost all (97%) of the 123 patients included in this analysis were triple-class refractory and nearly half (42%) were penta-drug refractory*. The trial is part of the robust MagnetisMM multiple indication clinical research program that expands to additional patient populations over time, with ongoing registration-intent trials that explore elranatamab both as monotherapy and in combination with standard or novel therapies, spanning multiple patient populations from newly diagnosed multiple myeloma, double-class exposed disease and RRMM.

In November 2022, Pfizer announced elranatamab received Breakthrough Therapy Designation from the Food and Drug Administration (FDA) for the treatment of RRMM. Elranatamab has also been granted Orphan Drug Designation by the FDA and the European Medicines Agency (EMA) for the treatment of MM. The FDA and EMA have granted elranatamab Fast Track Designation and the PRIME scheme, respectively, for the treatment of patients with RRMM. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has also granted elranatamab Innovative Medicine Designation and the Innovation Passport for the treatment of MM.

* Penta-drug refers to at least 2 proteosome inhibitors, 2 immunomodulatory drugs, and 1 anti-CD38 antibody.

About Multiple Myeloma

Multiple myeloma is a blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection. There are over 34,000 new cases of multiple myeloma diagnosed annually in the U.S. and 176,000 globally.1,2 Despite treatment advances, there is currently no cure. The median overall survival is just over five years, and most patients receive four or more lines of therapy.3

On December 10, 2022 Orca Bio, a late-stage biotechnology company developing high-precision cell therapies for the treatment of cancer, genetic blood disorders and autoimmune diseases, reported updated positive clinical data on its lead investigational cell therapy, Orca-T, during an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Orca Bio, DEC 10, 2022, View Source [SID1234625058]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data demonstrated a significant improvement in relapse-free survival (RFS) at one year with 87% in 71 patients who received Orca-T and busulfan, fludarabine and thiotepa (BFT) conditioning. BFT is the preferred conditioning regimen used in Precision-T, the ongoing Phase 3 pivotal study of Orca-T. Additionally, across all 151 patients, there was an increase in graft-versus-host disease-free, relapse-free survival (GRFS) rates and overall survival rates at one year with Orca-T compared to an independent cohort.

"Today, providers must balance treatment decisions with the goal of fighting cancer while minimizing toxicities. With a standard allogeneic transplant, highly myeloablative conditioning regimens can lead to reduced rates of patient relapse, but can also increase rates of non-relapse mortality," said Everett Meyer, M.D., Ph.D., primary investigator. "It is encouraging to see that the use of Orca-T across multiple hematological malignancies resulted in a remarkable improvement in relapse-free and overall survival while lowering the rate of serious toxicities compared to standard of care allogeneic hematopoietic stem cell transplants."

The results of the patient subgroup conditioned with BFT were presented today along with pooled results from the single-center Phase 2 and multi-center Phase 1b trials from 151 patients treated with Orca-T with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndromes (MDS) and other hematological malignancies. For comparison purposes, an independent Center for International Blood and Marrow Transplant Research (CIBMTR)-based cohort was identified consisting of patients with AML, ALL or MDS who received a standard of care allogeneic hematopoietic stem cell transplant.

Results demonstrated that patients conditioned with BFT and treated with Orca-T experienced:

87% RFS at one year among all groups, including minimal residual disease positive acute leukemia patients.
81% GRFS at one year.
0% non-relapse mortality and only 5% moderate-to-severe chronic graft versus host disease at one year.
94% overall survival (OS) at one year.
In pooled results from all patients treated with Orca-T, patients experienced:

70% GRFS at one year compared to 21% in the CIBMTR-based cohort.
4% non-relapse mortality at one year compared to 10% in the CIBMTR-based cohort.
88% OS at one year compared to 68% in the CIBMTR-based cohort.
Importantly, Orca-T was manufactured reliably and delivered with vein-to-vein times of 72 hours or less across the U.S.

"These relapse-free and overall survival rates from more than 150 patients treated with Orca-T are very encouraging, and we are extremely pleased to see the strong results of patients who were given the preferred conditioning regimen used in our pivotal Phase 3 trial," said Ivan Dimov, Ph.D., co-founder and chief executive officer of Orca Bio. "These new data continue to reinforce the potential of this high-precision cell therapy to become a better treatment option for patients and transplant physicians. We remain laser-focused on advancing Orca-T through Precision-T and ultimately on delivering the therapy to more patients in need."

The full presentation will be made available on www.orcabio.com.

About Orca-T
Orca-T is an investigational high-precision allogeneic cellular therapy consisting of infusions containing regulatory T-cells, conventional T-cells and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration and is being studied to treat multiple hematologic malignancies.

On December 10, 2022 Incyte (Nasdaq:INCY) reported new data from two of its LIMBER (Leadership In MPNs and GVHD BEyond Ruxolitinib) trials evaluating monotherapy and combination strategies using ruxolitinib (Jakafi) with parsaclisib, its investigational phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, and INCB00928 (zilurgisertib), its activin receptor-like kinase (ALK2) inhibitor, in patients with myelofibrosis (MF) (Press release, Incyte, DEC 10, 2022, View Source [SID1234625057]). These Phase 2 and Phase 1/2 trials (Abstract #236 and Abstract #1714, respectively) were presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, held December 10-13, 2022, in New Orleans and virtually1,2.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"MF is a rare, chronic blood cancer, and despite the advancements made in treatment, additional options are needed"

"Despite the significant advances we have made in the treatment of myeloproliferative neoplasms (MPNs) like MF, a need for additional options remains for those who have an inadequate response to or are unable to tolerate current therapies," said Peter Langmuir, M.D., Vice President, Oncology Drug Development, Incyte. "The parsaclisib and ruxolitinib data presented at ASH (Free ASH Whitepaper) demonstrate the clinical potential of the combination to improve upon the standard of care and continue to support the safety profile. We look forward to building on these results through our Phase 3 LIMBER-304 and LIMBER-313 trials evaluating parsaclisib as an add-on to ruxolitinib and in the frontline setting, both of which are currently underway."

Final results from the Phase 2 trial (Abstract #236; NCT02718300) evaluating the efficacy and safety of add-on parsaclisib to ruxolitinib for patients with MF who had a suboptimal response to ruxolitinib resulted in additional spleen volume reduction and improvement in symptom burden with add-on parsaclisib. Patients in the trial received parsaclisib daily for eight weeks in combination with stable dose ruxolitinib and then daily or weekly thereafter. Patients who received an all daily parsaclisib dosing schedule appeared to have a more durable efficacy profile compared with daily followed by weekly dosing of parsaclisib. Specifically:

At 12 weeks of treatment, 59.5% (25), 21.4% (9) and 4.8% (2) of patients who received all daily dosing experienced ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
Comparatively, 28.1% (9), 3.1% (1) and 0% of patients who received daily followed by weekly dosing experienced ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
At 24 weeks of treatment the reduction was maintained, with 50% (21), 28.6% (12) and 7.1% (3) patients who received all daily dosing experiencing ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
Comparatively, 12.5% (4), 12.5% (4) and 3.1% (1) of patients who received daily followed by weekly dosing experienced ≥10%, ≥25% and ≥35% reduction in spleen volume, respectively.
Addition of parsaclisib to ruxolitinib was generally well-tolerated, with limited grade 3 or 4 adverse events and treatment-emergent adverse event (TEAE)-related discontinuations. TEAEs common to PI3Kδ inhibitors in lymphoma (e.g., hepatotoxicity, rash, colitis) were infrequent or absent with the addition of parsaclisib.
Serious TEAEs occurring in ≥2 patients overall included pneumonia (n=6; 2 daily/weekly, 1 all daily), fall (n=3; 2 daily/weekly, 1 all daily) and pyrexia (n=2; 1 daily/weekly, 1 all daily).
Overall, 9 patients (5 daily/weekly, 4 all daily) had a TEAE leading to parsaclisib discontinuation, and 4 patients (2 daily/weekly, 2 all daily) had a TEAE leading to ruxolitinib discontinuation.
"MF is a rare, chronic blood cancer, and despite the advancements made in treatment, additional options are needed," said Abdulraheem Yacoub, Associate Professor, Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center. "I am encouraged by these findings and the potential of parsaclisib and ruxolitinib to be an efficacious combination therapy to help improve outcomes for certain patients living with MF."

Additionally, data from a Phase 1/2 open-label, dose escalation and expansion study (Abstract #1714; NCT04455841) assessing the safety and tolerability of INCB00928 (zilurgisertib), a potent and selective ALK2 inhibitor, as monotherapy or in combination with ruxolitinib in patients with anemia due to MF were presented at ASH (Free ASH Whitepaper). Anemia occurs in more than one-third of patients at MF diagnosis and can be exacerbated during treatment3,4. Initial results of the study observed reduction in post-dose hepcidin levels at all dose levels and observed improvements in anemia among patients treated in both the monotherapy and combination cohorts, which suggest the potential for therapeutic activity. The data also support once-daily dosing of INCB00928 and continued dose escalation to achieve optimal exposure. Treatment with INCB00928 monotherapy and in combination with ruxolitinib resulted in predominantly grade 1/2 TEAEs and no dose-limiting toxicities (DLTs). Few grade ≥3 TEAEs were observed, including thrombocytopenia in two patients with baseline grade 2 thrombocytopenia, and neutropenia in one patient with baseline grade 2 neutropenia. No TEAEs led to study drug discontinuation.

More information regarding the congress and the more than 50 abstracts from Incyte’s oncology portfolio being featured at the meeting is available on the ASH (Free ASH Whitepaper) website: View Source

About Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs) are a closely related group of blood cancers in which the bone marrow functions abnormally. The bone marrow is where the body’s blood cells are made. MPNs are progressive blood cancers that can strike anyone at any age, but they are more common in older adults. Estimates of the prevalence of MPNs vary, but analysis of claims data suggests there may be as many as 200,000 people in the U.S. living with the most prevalent MPNs: myelofibrosis, polycythemia vera or essential thrombocythemia5.

About LIMBER

Incyte is a leader in the discovery and development of therapies for patients with myeloproliferative neoplasms (MPNs) and graft-versus-host disease (GVHD). The Leadership In MPNs and GVHD BEyond Ruxolitinib (LIMBER) program is designed to evaluate multiple monotherapy and combination strategies to improve and expand treatments for patients with MPNs and GVHD. The program currently has three key areas of focus: development of a new, once-daily formulation of ruxolitinib; ruxolitinib-based combinations with new targets such as PI3Kδ, BET and ALK2; and new therapeutic options such as mutant CALR.

About Jakafi (ruxolitinib)

Jakafi (ruxolitinib) is a JAK1/JAK2 inhibitor approved by the U.S. FDA for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea; intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults; steroid-refractory acute GVHD in adult and pediatric patients 12 years and older; and chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older6.

Jakafi is marketed by Incyte in the United States and by Novartis as Jakavi (ruxolitinib) outside the United States. Jakafi is a registered trademark of Incyte Corporation. Jakavi is a registered trademark of Novartis AG in countries outside the United States.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi (ruxolitinib) may cause low platelet, red blood cell, and white blood cell counts. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will do a blood test to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Cancer: Some people have had certain types of non-melanoma skin cancers during treatment with Jakafi. Your healthcare provider will regularly check your skin during your treatment with Jakafi. Tell your healthcare provider if you develop any new or changing skin lesions during treatment with Jakafi.

Increases in cholesterol: You may have changes in your blood cholesterol levels during treatment with Jakafi. Your healthcare provider will do blood tests to check your cholesterol levels about every 8 to 12 weeks after you start taking Jakafi, and as needed.

Increased risk of major cardiovascular events such as heart attack, stroke or death in people who have cardiovascular risk factors and who are current or past smokers while using another JAK inhibitor to treat rheumatoid arthritis: Get emergency help right away if you have any symptoms of a heart attack or stroke while taking Jakafi, including: discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back, severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw, pain or discomfort in your arms, back, neck, jaw, or stomach, shortness of breath with or without chest discomfort, breaking out in a cold sweat, nausea or vomiting, feeling lightheaded, weakness in one part or on one side of your body, slurred speech

Increased risk of blood clots: Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with Jakafi, including: swelling, pain, or tenderness in one or both legs, sudden, unexplained chest or upper back pain, shortness of breath or difficulty breathing

Possible increased risk of new (secondary) cancers: People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers. People who smoke or who smoked in the past have an added risk of new cancers.

The most common side effects of Jakafi include: for certain types of myelofibrosis (MF) and polycythemia vera (PV) – low platelet or red blood cell counts, bruising, dizziness, headache, and diarrhea; for acute GVHD – low platelet counts, low red or white blood cell counts, infections, and swelling; and for chronic GVHD – low red blood cell or platelet counts and infections including viral infections.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Call your doctor for medical advice about side effects.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had low white or red blood cell counts, have or had tuberculosis (TB) or have been in close contact with someone who has TB, had shingles (herpes zoster), have or had hepatitis B, have or had liver or kidney problems, are on dialysis, have high cholesterol or triglycerides, had cancer, are a current or past smoker, had a blood clot, heart attack, other heart problems or stroke, or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change your dose or stop taking Jakafi without first talking to your healthcare provider.

Women should not take Jakafi while pregnant or planning to become pregnant. Do not breastfeed during treatment with Jakafi and for 2 weeks after the final dose.

Please see the Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

You may also report side effects to Incyte Medical Information at 1-855-463-3463.