On November 5, 2021 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision oncology biopharmaceutical company, reported the promotion of current vice president and head of clinical development, Dr. Emil T. Kuriakose, to chief medical officer (CMO) (Press release, Calithera Biosciences, NOV 5, 2021, View Source [SID1234594584]). Dr. Kuriakose will succeed Dr. Keith Orford, who has been appointed to Calithera’s board of directors.

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"Emil has a proven track record of leading clinical programs across multiple disease areas, and he is well-suited to assume this role at Calithera based on his accomplishments and four-year tenure with the company," said Susan Molineaux, PhD, chief executive officer of Calithera. "Keith played a critical role in building the company’s clinical team during his seven years at Calithera. We are deeply appreciative of his contributions to-date and look forward to his continued strategic input in his new role as a member of our board."

During his time at Calithera, Dr. Kuriakose has overseen the advancement of the company’s clinical development programs, including the arginase inhibitor programs in oncology and cystic fibrosis, as well as multiple telaglenastat trials. As an integral member of the diligence team, Dr. Kuriakose played a key role in the company’s recent successful acquisition of sapanisertib and mivavotinib from Takeda Pharmaceuticals, and he led formulation of the clinical development plan for the newly acquired assets. Prior to Calithera, Dr. Kuriakose led global clinical development programs, most recently with Novartis. Dr. Kuriakose completed his clinical training in hematology/oncology at Weill Cornell Medical College, including a research fellowship at Memorial Sloan Kettering Cancer Center, and he completed his residency training in internal medicine at UT Southwestern Medical Center in Dallas, TX. Dr. Kuriakose received his medical degree from Stony Brook University School of Medicine and his Bachelor of Science in neuroscience from New York University.

"I have great confidence in our new strategic focus to develop targeted therapies for biomarker-specific patient populations," said Dr. Kuriakose. "I have had the privilege of working alongside Keith for the last four years and look forward to continuing our partnership as he joins the board."

Dr. Orford will assume the seat being vacated by current board member Jean M. George. Ms. George, a biotech investment and business development industry veteran, has served on the Calithera Board of Directors since 2012.

On November 5, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a company applying innovative diagnostics to inform disease management and improve patient outcomes, reported the publication of a study validating performance of a novel algorithm designed to integrate the DecisionDx-Melanoma gene expression profile (GEP) test with clinicopathologic features (i31-GEP SLNB) to determine sentinel lymph node biopsy (SLNB) positivity risk in patients with cutaneous melanoma (Press release, Castle Biosciences, NOV 5, 2021, View Source [SID1234594614]).

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DecisionDx-Melanoma is Castle’s risk-stratification GEP test that is designed to predict 5-year risk of metastasis as well as metastasis to the SLN. The test’s Integrated Test Result (ITR) includes the traditional class designation of lowest risk (Class 1A), increased risk (Class 1B/2A) or highest risk (Class 2B), as well as a more precise risk prediction for both SLNB positivity and risk of recurrence, distant metastasis and melanoma survival in patients with stage I, II or III melanoma through the i31- GEP algorithms (SLNB and Risk of Recurrence). The i31-GEP SLNB and ROR are distinct independently validated algorithms that integrate clinicopathologic features with the DecisionDx-Melanoma score.

"The majority of patients who undergo the SLNB surgical procedure receive a negative result," said Robert Cook, Ph.D., senior vice president of research and development of Castle Biosciences and study author. "The i31-GEP SLNB clinical validation data showed that integrating clinicopathologic risk factors with the DecisionDx-Melanoma test provided very high correlation between the predicted and the actual, or observed, rates and a high sensitivity in identifying patients at low risk for SLN metastasis who may be able to safely avoid the SLNB procedure. Importantly, the study demonstrated that the DecisionDx-Melanoma test result was the most important variable in predicting SLN positivity."

The article, titled "Integrating 31-Gene Expression Profiling with Clinicopathologic Features to Optimize Cutaneous Melanoma Sentinel Lymph Node Metastasis Prediction," was published in the peer-reviewed journal JCO Precision Oncology and can be accessed here. The study highlights the development and validation of the i31-GEP SLNB algorithm.

Study background:

National guidelines recommend that an SLNB be offered to patients with >10% likelihood of SLN positivity (typically thought to encompass T2-T4 tumors), but do not recommend SLNB for patients who are thought to have <5% likelihood of a positive SLN (typically thought to encompass T1a tumors without high-risk features).
The decision to perform SLNB is less certain for patients with higher-risk T1 melanomas (T1a tumors with high-risk features or T1b tumors) in which a positive node is expected 5%-10% of the time.
The integrated DecisionDx-Melanoma test result for SLNB (i31-GEP SLNB) was designed to combine DecisionDx-Melanoma’s output, a risk assignment based on GEP analysis, with clinicopathologic risk factors.
The study describes the development and validation of the i31-GEP SLNB, which utilizes a neural network algorithm to integrate the continuous DecisionDx-Melanoma result with patient histologic and clinical features.
The i31-GEP SLNB algorithm was developed in a cohort of 1,398 patients and independently validated on a cohort of 1,674 patients.
Study findings:

In comparison to all clinicopathologic features considered, the DecisionDx-Melanoma continuous score was the most important variable for prediction of a positive SLN, with a P value of less than 0.001.
The i31-GEP SLNB algorithm demonstrated a very high correlation comparing predicted versus observed SLN positivity rates of 0.999 (1.0 is complete correlation).
The i31-GEP SLNB algorithm demonstrated a highly sensitive prediction of SLN positivity rates (95.1%) compared to observed rates.
In patients with T1-T4 tumors, the i31-GEP SLNB increased the percentage of patients predicted to have <5% SLN positivity risk from 8.5%, using current staging guidelines, to 27.7%.
Specifically, for patients predicted to have 5%-10% risk by current guidelines, the i31-GEP SLNB restratified 63% of cases to an SLN positivity risk of <5% or >10%.
The i31-GEP SLNB identified patients with <5% SLN positivity risk, who might forego SLNB, or those with >10% SLN positivity risk, who might be offered SLNB, according to current guidelines.
These data demonstrated that the i31-GEP SLNB could provide personalized risk estimates for SLN positivity, potentially reducing the number of SLNBs and provide additional information to appropriately identify patients at the highest risk of having a positive SLN.
This personalized information may help clinicians and their patients make more informed decisions about the SLNB surgical procedure.
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an integrated DecisionDx-Melanoma test result. Through June 30, 2021, DecisionDx-Melanoma has been ordered 78,277 times for use in patients with cutaneous melanoma.

More information about the test and disease can be found at www.CastleTestInfo.com.

On November 5, 2021 bluebird bio, Inc. (NASDAQ: BLUE) reported financial results and business highlights for the third quarter ended September 30, 2021 (Press release, bluebird bio, NOV 5, 2021, View Source [SID1234594585]).

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"This quarter was about preparing for the completion of the separation of bluebird bio and 2seventy bio and realizing the value of two independent companies," said Andrew Obenshain, chief executive officer, bluebird bio. "Notably this quarter, we secured additional capital through the close of a private financing and completion of the sale of our manufacturing facility in North Carolina and continued to make meaningful progress with our product pipeline, including filing the US biologics licensing application for beti-cel for beta-thalassemia. I am excited for what lies ahead for both bluebird and 2seventy bio, and the impact that both companies will have for patients and their families."

BUSINESS SEPARATION RECENT HIGHLIGHTS

COMPLETION OF SEPARATION – On November 4, 2021, bluebird bio completed the tax-free spin-off of its oncology business, 2seventy bio, Inc. bluebird bio will continue its work focused on severe genetic diseases, with three near-term opportunities to bring transformative gene therapies to patients and their families in the U.S. 2seventy began regular-way trading on the NASDAQ under the stock ticker symbol "TSVT" on November 5, 2021. bluebird bio will continue to trade under the stock ticker symbol "BLUE".
PRIVATE FINANCING – Prior to the separation on September 8, 2021, bluebird bio announced that it has entered into an agreement for a $75 million private placement of common stock and common stock equivalents with a healthcare investment fund selected as part of a competitive process.
STARTING CASH POSITION – As of completion of the separation, bluebird’s restricted cash, cash and cash equivalents and marketable securities balance is approximately $518.5M. Increased fiscal discipline, including through projected real estate savings with the move of the Company’s headquarters to Assembly Row in Somerville, Massachusetts, and the wind down of European operations, together with the potential sale of priority review vouchers that would be issued with anticipated U.S. regulatory approvals of biologics licensing applications for beti-cel and eli-cel will be sufficient to fund operations for bluebird bio into 2023 under current business plans.
RECENT HIGHLIGHTS

β-THALASSEMIA

BETI-CEL SUBMISSION – On September 21, 2021, bluebird bio announced it completed the rolling submission of its Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for betibeglogene autotemcel (beti-cel) gene therapy in adult, adolescent and pediatric patients with β-thalassemia who require regular red blood cell transfusions, across all genotypes. If approved, beti-cel will be the first hematopoietic (blood) stem cell (HSC) ex-vivo gene therapy for patients in the United States.
COMPANY

NEW HEADQUARTERS – Today, bluebird bio announced its new headquarters in Assembly Row, designed to reflect modern ways of working and estimated to result in more than $120 million in cost savings over the next six years for the company. bluebird signed a long-term lease with Federal Realty Investment Trust (FRIT) for the 61,000 square foot facility located at 455 Grand Union in Somerville, MA.
BOARD OF DIRECTORS – This quarter, bluebird bio announced the appointment of Najoh Tita-Reid (Logitech) and Lis Leiderman, M.D. (Decibel Therapeutics) to its board of directors. They are joined on the bluebird bio board of directors by Mark Vachon (chairman – formerly of GE), John Agwunobi, M.D. (Herbalife Nutrition), Wendy Dixon, Ph.D. (formerly of Bristol-Myers Squibb), Nick Leschly (2seventy bio) and Andrew Obenshain (bluebird bio).
EUROPE WIND DOWN – Following the August 9, 2021 announcement that it intended to wind down operations in Europe, on October 21, bluebird bio announced that it will withdraw its regulatory marketing authorization for SKYSONA from the European Union, and its marketing application for SKYSONA from the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom (UK). bluebird bio, Inc. also anticipates withdrawing marketing authorizations for ZYNTEGLO from both the EU and the UK by early 2022. The company expects to continue activities for the long-term follow-up of patients previously enrolled within the European clinical trial programs as planned, but does not intend to initiate any new clinical trials in Europe for the beta-thalassemia, cerebral adrenoleukodystrophy or sickle cell disease programs.
MANAGEMENT APPOINTMENT – On November 4, 2021, bluebird bio announced the appointment of Gina Consylman as Chief Financial Officer, effective upon the completion of the spin-off transaction of 2seventy bio.
UPCOMING ANTICIPATED MILESTONES

beti-cel: Acceptance of the BLA to the US Food and Drug Administration for beti-cel for beta-thalassemia expected this month.
eli-cel: The BLA filing for elivaldogene autotemcel (eli-cel, Lenti-D) for patients with cerebral adrenoleukodystrophy (CALD) is on track for the end of 2021.
eli-cel: The company is in active communication with the FDA to resolve the clinical hold.
bb1111: The company plans to host an investor event on November 18th, 2021, to share further detail on its sickle cell disease program and path to regulatory approval.
American Society of Hematology Annual Meeting: bluebird will present new data on beti-cel and bb1111 at ASH (Free ASH Whitepaper) 2021, including long-term results for beti-cel in adult and pediatric patients with beta-thalassemia, new analyses from Groups A&C of the ongoing Phase 1/2 HGB 206 study of bb1111 for sickle cell disease, and sustained improvements in patient reported quality of life in Group C.
THIRD QUARTER 2021 FINANCIAL RESULTS

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2021, and December 31, 2020, were $970.7 million and $1.27 billion, respectively. The decrease in cash, cash equivalents and marketable securities is primarily related to cash used in support of ordinary course operating activities.
Revenues: Total revenues were $22.7 million for the three months ended September 30, 2021, compared to $19.3 million for the three months ended September 30, 2020. Total revenues were $42.9 million for the nine months ended September 30, 2021, compared to $240.0 million for the nine months ended September 30, 2020. The increase for the three-month period was primarily driven by our collaborative arrangement revenue recognized under our collaboration arrangement with BMS. The decrease for the nine-month period was primarily driven by a cumulative catch-up adjustment to revenue recorded in connection with the May 2020 BMS contract modification in the second quarter of 2020.
ABECMA Revenue: This quarter Bristol-Myers Squibb (BMS) reported total U.S. revenues of $67 million for ABECMA (idecabtagene vicleucel; ide-cel). bluebird bio reported a net collaboration revenue of $14.8 million for 3Q, which includes the company’s share of revenue and costs associated with the commercialization of ABECMA in the U.S.
R&D Expenses: Research and development expenses were $131.4 million for the three months ended September 30, 2021, compared to $140.4 million for the three months ended September 30, 2020. Research and development expenses were $429.6 million for the nine months ended September 30, 2021, compared to $450.9 million for the nine months ended September 30, 2020. The decrease for the three-month period was primarily driven by decreased collaboration research funding costs resulting from a decrease in expense recognized under our collaboration arrangement with BMS. The decrease for the nine-month period was primarily driven by decreased manufacturing expenses.
SG&A Expenses: Selling, general and administrative expenses were $68.3 million for the three months ended September 30, 2021, compared to $68.0 million for the three months ended September 30, 2020. Selling, general and administrative expenses were $229.7 million for the nine months ended September 30, 2021, compared to $210.0 million for the nine months ended September 30, 2020. The increase for both periods was primarily driven by an increase in fees associated with the spinoff of 2seventy bio as well as increased employee compensation, benefit, and other headcount related expenses.
Restructuring Expenses: Restructuring expenses were $20.2 million and $24.8 million for the three months and nine months ended September 30, 2021, respectively. These costs are related to a reduction in the workforce, primarily driven by the wind down of operations in Europe.
Net Loss: Net loss was $216.8 million for the three months ended September 30, 2021, compared to $194.7 million for the three months ended September 30, 2020. Net loss was $664.3 million for the nine months ended September 30, 2021, compared to $418.8 million for the nine months ended September 30, 2020.

On November 5, 2021 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that abstracts on three clinical trials of the company’s novel drug candidate, olverembatinib (HQP1351), have been selected for poster presentations and one oral presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Ascentage Pharma, NOV 5, 2021, View Source;ascentage-pharma-to-present-three-studies-of-olverembatinib-hqp1351-a-novel-drug-candidate-for-the-treatment-of-drug-resistant-leukemia-in-abstracts-including-one-oral-report-at-ash-annual-meeting-301417333.html [SID1234594615]). Presenter, Qian Jiang, MD, and Xiaojun Huang, MD, from the Hematology Department of Peking University People’s Hospital are the principal investigators of the study selected for oral presentation. This is the fourth consecutive year in which studies of olverembatinib were selected for oral presentation by the ASH (Free ASH Whitepaper) Annual Meeting, demonstrating strong recognition of the drug candidate’s promising efficacy and safety by the international hematology community.

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Olverembatinib is a novel third-generation BCR-ABL tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma for the treatment of patients with chronic myeloid leukemia (CML) resistant to first- and second-generation TKIs, including those with the T315I mutation, which confers resistance against these agents. The New Drug Application (NDA) submitted by Ascentage Pharma for olverembatinib for the treatment of patients with T315I-mutated CML in chronic-phase (CML-CP) or accelerated-phase (CML-AP) is currently under review in China and has already been granted the Priority Review status. Moreover, olverembatinib was granted a Breakthrough Therapy designation by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) for the treatment of patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs.

The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology field, bringing together the latest and most cutting-edge research and other scientific and clinical developments in hematology. The 63rd ASH (Free ASH Whitepaper) Annual Meeting will take place on December 11-14, 2021, both virtually and in-person in Atlanta, Georgia, United States. This year, six abstracts on three of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax [APG-2575], and pelcitoclax [APG-1252]) have been selected by the ASH (Free ASH Whitepaper) Annual Meeting for poster or oral presentations (information on those abstracts about lisaftoclax [APG-2575] and pelcitoclax [APG-1252] are available in a separate press release published in parallel).

Drug Candidate

Abstract Title

Abstract#

Format

Olverembatinib

(HQP1351)

Updated Safety and Efficacy Results of Phase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML)

311

Presentation

Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL1T315I-Mutated Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP)

3598

Poster Presentation

Trial in Progress: Phase 1b Bridging Study of the Pharmacokinetic (PK), Safety, and Efficacy of Orally Administered Olverembatinib (HQP1351) in Patients with Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

2551

Poster Presentation

Lisaftoclax (APG-2575)

A Phase 1 Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor (BCL-2i), in Patients (pts) with Certain Relapsed or Refractory (R/R) Hematologic Malignancies (HMs)

3730

Poster Presentation

Trial in Progress: Phase 1b Study of Lisaftoclax (APG-2575) As a Single Agent or Combined with Other Therapeutic Agents in Patients with Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (R/R CLL/SLL)

1554

Poster Presentation

Pelcitoclax (APG-1252)

Antitumor Activity of Dual BCL-2/BCL-xl Inhibitor Pelcitoclax (APG-1252) in Natural Killer/T-Cell Lymphoma (NK/TCL)

2062

Poster Presentation

"These data to be reported at the 2021 ASH (Free ASH Whitepaper) Annual Meeting are very encouraging as they demonstrated olverembatinib’s promising efficacy and tolerability profiles. This is the fourth year in which the clinical progress of this drug candidate has been selected for oral presentation at the ASH (Free ASH Whitepaper) Annual Meeting, a strong indication of the international hematology community’s recognition of olverembatinib’s potential as a new treatment option for patients with CML," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "As China’s first and the world’s second third-generation BCR-ABL inhibitor, olverembatinib offers patients with CML a potential new treatment with clear efficacy and potentially enhanced safety. We hope that olverembatinib will soon be granted market authorization so that patients with CML in China and around the world can start benefiting from this novel therapeutic."

These abstracts selected for presentations at 2021 ASH (Free ASH Whitepaper) Annual Meeting are as follows:

Updated Safety and Efficacy Results of Phase 1 Study of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML)

Format: Oral Presentation
Abstract: 311
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Mechanisms of resistance and expanded therapies
Time: Saturday, December 11, 2021; 5:00 PM EDT
Highlights
– This Chinese, open-label, multicenter, Phase I trial evaluated the safety and efficacy of olverembatinib in adults with CML-CP or CML-AP. Eligible patients had CML-CP or CML-AP resistant or intolerant to first- and second-generation TKIs. Olverembatinib was orally administered once every other day (QOD) in 28-day cycles and at 11 dose cohorts ranging from 1 to 60 mg. This study reports data on patients with long-term follow-up.

– From October 26, 2016, through February 2, 2021 (data cut-off date), 101 patients with CML-CP (n=86) or CML-AP (n=15) were enrolled and treated with olverembatinib. A total of 71 (70.3%) patients were male, the median age was 40 (range, 20-64) years, and the median (range) interval from diagnosis to initial olverembatinib treatment was 6.0 (0.3-15.2) years. In all, 84 (83.2%) patients received ≥ 2 prior lines of TKI-therapies, and 63 (62.4%) harbored the T315I mutation. At baseline, compound mutations were detected in 11 (10.9%) patients, of whom 7 (63.6%) had the BCR-ABL1T315I genotype. A total of 20 (19.8%) patients had 2 (n=13) or ≥ 3 (n=7) mutations. The median follow-up was 30.8 (1.2-51.8) months. As of the data cutoff date, 81 (80.2%) of 101 patients continued on the treatment, 18 (17.8%) were treated for > 3 years, and 5 (5%) for > 4 years.

– Of evaluable patients without baseline responses, 97.0% had complete hematologic responses (CHR), 62.1% had complete cytogenetic responses (CCyR), and 51.0% had major molecular responses (MMR).

– Among patients in CML-CP, most evaluable patients with T315I mutations experienced CHR (100%), MCyR (83.7%), or MMR (71.2%).

– Among patients in CML-AP, 80.0% experienced CHR and 54.5% each MCyR or MMR.

At 36 months, the progression-free survival (PFS) rate was 96.3% (89.1%-98.8%) in patients with CML-CP and 71.4% (40.6%‒88.2%) in those with CML-AP.

Treatment responses were durable and unaffected by baseline BCR-ABL1 mutational status. Corresponding values in patients with> 4 years of treatment were 100% (CHR), 80% (CCyR), and 60% (MMR). The mean PFS rate was 100% at 36 or 48 months and not reached (NR-NR) at 60 months.

– Most treatment-related adverse events (TRAEs) were grade 1 or 2.

– The most frequent nonhematologic adverse event (AE) was (mostly grade 1 or 2) skin hyperpigmentation (86.1%). Grade ≥ 3 nonhematologic AEs included hypertriglyceridemia (10.9%), pyrexia (6.9%), and proteinuria (5.0%).

– The most common hematologic TRAE was thrombocytopenia in 78 (77.2%) patients, including 52 (51.5% of total population) with grade ≥ 3. Leukopenia was grade ≥ 3 in 21 (20.8%) patients but not serious, while anemia was grade ≥ 3 in 16 (15.8%) patients.

– Conclusions: In patients with TKI-resistant CML-CP or CML-AP and long-term treatment, olverembatinib was efficacious and well tolerated.

Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL1T315I-Mutated Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP)

Format: Poster Presentation
Abstract: 3598
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster III
Time: Monday, December 13, 2021; 6:00 PM – 8:00 PM EDT
Highlights:
– HQP1351-CC201 and HQP1351-CC202 are Chinese open, single-arm, multicenter pivotal Phase II trials evaluating the safety and efficacy of olverembatinib in adults with TKI-resistant (BCR-ABL1T315I-mutated) CML-CP and CML-CP, respectively. Olverembatinib was administered at 40 mg orally QOD for 28-day cycles.

– As of the data cutoff of August 25, 2020, HQP1351-CC201 had enrolled 41 patients with CML-CP, of whom 32 (78%) completed ≥ 12 cycles. The median follow-up was 13 (3.1-16.3) months. After ≥ 12 treatment cycles in patients without responses at baseline, all 31 (100%) experienced CHR (10 other patients had CHR at baseline); 31/41 (75.6%) MCyR; 28/41 (68.3%) CCyR; and 23/41 (56.1%) MMR. At 12 months, the PFS rate was 89.3%, and overall survival (OS) 100%.

– As of the data cutoff of July 27, 2020, HQP1351-CC202 had enrolled 23 patients with CML-CP, of whom 14 (61%) had completed≥ 12 cycles. The median (range) follow-up was 13.5 (1.4-15.2) months. After ≥ 12 treatment cycles in patients without responses at baseline, 17/23 (73.9%) experienced MaHR; 12/23 (52.2%) MCyR; 11/23 (47.8%) CCyR; and 9/23 (39.1%) MMR. At 12 months, the PFS rate was 74.1%, and the OS 91.3%.

– In HQP1351-CC201, the most frequent grade 3-4 TRAE was thrombocytopenia (48.8%), and no treatment-related deaths occurred.

– In HQP1351-CC202, the most frequent grade 3-4 TRAE was thrombocytopenia (56.5%).

– Conclusions: Olverembatinib was efficacious and well tolerated when administered as monotherapy in patients with TKI-resistant CML-CP or CML-AP and the BCR-ABL1T315I mutation.

Trial in Progress: Phase 1b Bridging Study of the Pharmacokinetic (PK), Safety, and Efficacy of Orally Administered Olverembatinib (HQP1351) in Patients with Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Format: Poster Presentation
Abstract: 2551
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster II
Time: Sunday, December 12, 2021; 6:00 PM – 8:00 PM EDT
Highlights:
– This open-label bridging trial in the US is evaluating the PK, efficacy, and safety of olverembatinib administered orally QOD in adults who have CML-CP, CML-AP or blast-phase CML (CML-BP) and Ph+ ALL.

– This study is currently recruiting patients, with enrolled individuals being allocated to three dose cohorts: 30, 40, or 50 mg QOD orally. Endpoints of this study include PK, antitumor activity, and safety.

On November 5, 2021 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported the presentation of data from its ex vivo research and development efforts in two poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place in Atlanta, GA and virtually from December 11-14, 2021 (Press release, Intellia Therapeutics, NOV 5, 2021, View Source [SID1234594586]).

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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

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"As we continue to advance our full-spectrum strategy, we look forward to sharing preclinical data from our ex vivo platform with the research community at this year’s ASH (Free ASH Whitepaper) Annual Meeting," said Intellia Chief Scientific Officer Laura Sepp-Lorenzino, Ph.D. "The data will feature our novel allogeneic technology designed to overcome rejection by host T and NK cells without the need for host immune suppression, as well as highlight our clinical-scale manufacturing process developed for NTLA-5001, our TCR-based T cell therapeutic candidate for the treatment of acute myeloid leukemia. Together, the data support our progress toward developing engineered cell therapies with the potential to transform the lives of people living with life-threatening diseases."

ASH Annual Meeting Poster Presentations

Title: A Novel Strategy for Off-the-shelf T Cell Therapies Evading Host T Cell and NK Cell Rejection
Abstract number: 1711
Date/Time: Saturday, December 11, 2021, 5:30 p.m. – 7:30 p.m. ET
Location: Georgia World Congress Center, Hall B5
Presenting Author: Yong Zhang, Ph.D., associate director, Cell Therapy

Title: Clinical-scale Production and Characterization of NTLA-5001 – a Novel Approach to Manufacturing CRISPR/Cas9 Engineered T cell Therapies
Abstract number: 3881
Date/Time: Monday, December 13, 2021, 6:00 p.m. – 8:00 p.m. ET
Location: Georgia World Congress Center, Hall B5

Presenting Author: Daniel Cosette, senior scientist, Process Development

Additional data collected will be included in final meeting presentations. All abstracts for the ASH (Free ASH Whitepaper) Annual Meeting will be available on ASH (Free ASH Whitepaper)’s website here.