On November 5, 2021 Servier, a growing leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported new data in acute myeloid leukemia (AML) to be presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 11 – 14, 2021 (Press release, Servier, NOV 5, 2021, View Source [SID1234594616]).

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"Our growing oncology portfolio is designed to tackle hard-to-treat cancers and deliver new therapies for patients in need," said David K. Lee, Chief Executive Officer of Servier Pharmaceuticals. "At this year’s ASH (Free ASH Whitepaper) meeting, we are proud to present new data demonstrating significant clinical outcomes for patients living with AML."

"We look forward to sharing our findings with the medical community around the world, leveraging our leadership in oncology to strengthen our commitment to patients with hematological malignancies," said Claude Bertrand, Executive Vice President, R&D, Servier Group.

Servier abstracts being presented at ASH (Free ASH Whitepaper) include:

Abstract Title

Lead Author

Presentation Type/#

Session Title

Session Date/Time

Acute Myeloid Leukemia

AGILE: A Global, Randomized, Double-Blind, Phase 3 Study
of Ivosidenib + Azacitidine Versus Placebo + Azacitidine in
Patients with Newly Diagnosed Acute Myeloid Leukemia

Pau Montesinos, M.D., Ph.D., et. al.

Oral

Abstract #697

616. Acute Myeloid Leukemias:
Investigational Therapies, Excluding
Transplantation and Cellular
Immunotherapies: Targeted Therapies
and Novel Therapies

Monday, December 13 at 2:45 pm ET

Updated Survival and Response Analyses from a Phase 1
Study of Ivosidenib or Enasidenib Combined with Induction
and Consolidation Chemotherapy in Patients with Newly
Diagnosed AML with an IDH1 or IDH2 Mutation

Eytan M. Stein, M.D, et. al.

Poster

Abstract #1276

616. Acute Myeloid Leukemias:
Investigational Therapies,
Excluding Transplantation and Cellular
Immunotherapies: Poster I

Saturday, December 11 at 5:30 pm ET

Acute Lymphoblastic Leukemia

Safety and Pharmacokinetics of Calaspargase Pegol in
Adults with Newly Diagnosed Philadelphia-Negative ALL: A Phase
2/3 Study

Wendy Stock, M.D., et. al.

Abstract Only

N/A

N/A

About NCT03173248 AGILE Phase 3 AML Trial
The AGILE trial is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of TIBSOVO in combination with azacitidine compared with placebo in combination with azacitidine, in patients with newly diagnosed IDH1 mutant AML who are not candidates for intensive chemotherapy. The study’s primary endpoint is EFS, defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure is defined as failure to achieve complete remission (CR) by Week 24.

Other key secondary endpoints included complete remission rate (CR rate), defined as the proportion of participants who achieve a CR; overall survival (OS), defined as the time from date of randomization to the date of death due to any cause; CR and complete remission with partial hematologic recovery (CRh) rate, defined as the proportion of participants who achieve a CR or CRh; and objective response rate (ORR), defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS).

About NCT02632708 Phase 1 AML Trial
The NCT02632708 is a U.S., Phase 1 multicenter, clinical trial designed to evaluate the safety of ivosidenib (AG-120) or enasidenib (AG-221) when given in combination with standard AML induction and consolidation therapy. The study plans to evaluate up to 2 dose levels of AG-120 in participants with an isocitrate dehydrogenase protein 1 (IDH1) mutation and up to 2 dose levels of AG-221 in participants with an isocitrate dehydrogenase protein 2 (IDH2) mutation. AG-120 or AG-221 will be administered with 2 types of AML induction therapies (cytarabine with either daunorubicin or idarubicin) and 2 types of AML consolidation therapies (mitoxantrone with etoposide [ME] or cytarabine). After consolidation therapy, participants may continue on to maintenance therapy and receive daily treatment with single-agent AG-120 or AG-221 until relapse, development of an unacceptable toxicity, or hematopoietic stem cell transplant (HSCT). The study will end when all participants have discontinued study treatment. The primary endpoints are the percentage of participants with adverse events (AEs).

Other key secondary endpoints include recommended phase 2 dose when administered with induction and consolidation therapy; pharmacokinetics of AG-120 and AG-221 in plasma when administered with induction and consolidation therapy; 2-hydroxyglutarate (2-HG) Levels in Plasma; and Clinical Activity of AG-120 and AG-221 According to the 2003 Revised International Working Group (IWG) Criteria for AML.

About NCT04817761 Phase 2/3 ALL Trial
The NCT04817761 is a U.S., Phase 2/3 multi-center, open-label, single-arm clinical trial to confirm the recommended doses and to evaluate the safety and pharmacokinetics of calaspargase pegol for treatment of adults aged 22 to >65 years with newly-diagnosed Philadelphia-negative acute lymphoblastic leukemia (ALL). The study’s primary endpoint is adverse events (AEs) (Part 1) 30 days after administration at days 4, 5 and 6 in the remission induction phase, AEs (Part 2) 30 days after the last dose of the study drug in delayed intensification phase, plasma asparaginase activity (PAA) (Part 1) days 4, 5 and 6 for PAA samples, and nadir plasma asparaginase activity (NPAA) (Part 2).

Other key secondary endpoints include PAA level ≥0.1 U/mL at any time during remission induction phase and post-remission induction phase; PAA level ≥0.025, ≥0.1, ≥0.2, or ≥0.4 U/mL at predefined time points during remission induction phase and post-remission induction phase; PAA-derived maximum concentration (Cmax) after the remission induction phase day 4 dose; PAA-derived area under the PAA-time curve from time 0 to day 21 (AUC 0-21) after the remission induction phase day 4 dose (Part 1 and 2); minimal residual disease (MRD); complete remission (CR); survival, event-free survival (EFS),disease-free survival (DFS) and overall survival (OS), 2-year EFS, DFS, OS, 3-year EFS, DFS, OS; anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2).

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases in the U.S., and 43,000 cases in Europe each year. The majority of patients with AML eventually relapse. Relapsed or refractory AML has a poor prognosis. The five-year survival rate is approximately 27%. For 6% to 10% of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia.

About Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is the most common form of childhood acute leukemia. It is a rapidly progressing cancer that starts in the bone marrow and spreads into the blood, where it can cause problems elsewhere in the body, such as in the spleen, thymus, lymph nodes, liver, testicles, and the central nervous system. ALL represents approximately 12% of all leukemia cases worldwide, and about 80% of childhood leukemia cases. The five-year survival rate for children with ALL is now about 90%.

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 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 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, reported two abstracts pertaining to the potential use of lenzilumab in CAR-T will be presented at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 11-14, 2021 (Press release, Humanigen, NOV 5, 2021, View Source [SID1234594613]). The society counts more than 18,000 hematologists among its membership from more than 100 countries, and its annual meeting attracts over 30,000 professional attendees.

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"After completing a Phase 3 trial of lenzilumab, in 2021, for the treatment of patients hospitalized with COVID-19 pneumonia, we look forward to advancing our efforts to develop lenzilumab as a complementary therapy to potentially reduce CAR-T associated toxicities and to potentially improve outcomes for non-Hodgkin lymphoma patients," said Adrian Kilcoyne, Chief Medical Officer, Humanigen. "My experience working in the development of CAR-T therapies, which are now currently commercially available, suggests preventing toxicity and optimizing durable response rates remain challenges. Our plans include initiating the Phase 3 SHIELD study of lenzilumab in the first half of 2022 and we may be able to announce interim data at ASH (Free ASH Whitepaper) 2022."

Abstract #2777

Optimized Inhibition of GM-CSF in Preclinical Models of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy

Summary: The abstract describes the evaluation of differential targeting of the GM-CSF ligand using lenzilumab compared to targeting the GM-CSFα receptor using a different antibody in pre-clinical models. The research demonstrated significant differences on CAR-T cell functions and CAR-T cell-monocyte interactions when GM-CSF is neutralized with lenzilumab compared to blocking its receptor with other agents. A key finding is that lenzilumab neutralization of GM-CSF improved CAR-T cell proliferation, but the GM-CSFRα receptor blocking antibody may significantly inhibit CAR-T cell proliferation in a dose-dependent manner. This may have efficacy implications.

Presenter: Evandro Bezerra, MD, Mayo Clinic in Rochester, MN.
Session: 703. Cellular Immunotherapies: Basic and Translational: Poster II
Date: December 12, 2021; 6:00-8:00 PM EST

Abstract #175

A Phase 3 Randomized, Placebo-Controlled, Open-Label, Multi-Center Trial of Lenzilumab to Improve the Safety and Efficacy of CAR-T Cell Therapy in Adults with Relapsed or Refractory Large B-Cell Lymphoma* (The SHIELD Study)

Summary: The abstract describes a planned Phase 3 study of prophylactic lenzilumab administration in sequenced therapy with commercially available CAR-Ts to treat non-Hodgkin lymphoma. The study aim is to determine if lenzilumab can break the efficacy/toxicity linkage associated with CAR-T therapy thereby improving the toxicity and tolerance of CAR-T while maintaining or improving efficacy by neutralizing GM-CSF.

Presenter: Saad Kenderian, MD, principal investigator in the T Cell Engineering Lab at Mayo Clinic in Rochester, MN.
Session: 704. Cellular Immunotherapies: Clinical: Poster I
Date: December 11, 2021; 5:30 PM-7:30 PM EST

* The SHIELD study protocol has been adapted since submission of the abstract to include a broader patient population

On November 5, 2021 Calidi Biotherapeutics, Inc., a clinical-stage biotechnology company at the forefront of stem cell-based delivery of oncolytic viruses, reported that its physician advisor, Maciej S. Lesniak, MD, Department Chair of Neurological Surgery, Feinberg School of Medicine, Northwestern University, will present at the upcoming International Oncolytic Virotherapy Conference (IOVC), which will be held in hybrid format November 5 through November 7, 2021, as both a virtual event and an in-person meeting in Sedona, AZ (Press release, Calidi Biotherapeutics, NOV 5, 2021, View Source [SID1234594612]).

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Dr. Lesniak’s presentation: "Neural Stem Cell Delivery of Oncolytic Virotherapy for Glioma," will focus on the use of stem cells for virotherapy of cancer, featuring clinical findings from a first-in-human, open-label, Phase 1, dose-escalation trial demonstrating strong safety and efficacy signals for the NSC-CRAd-S-pk7 product, which Calidi refers to as NeuroNova (NNV), in patients with newly diagnosed high-grade glioma. Results from the clinical trial are published in The Lancet Oncology (June 29, 2021).

"Malignant glioma has been historically associated with dismal survival rates due to a lack of effective treatment," said Maciej S. Lesniak, MD, Department Chair of Neurological Surgery, Feinberg School of Medicine, Northwestern University. "I’m eager to share the promising results of our recently completed Phase 1 trial examining the safety and activity of NeuroNova in patients with advanced glioma."

In June 2021, Calidi reached an exclusive license agreement with Dr. Lesniak’s team at Feinberg School of Medicine, Northwestern University—designating exclusive commercialization rights to Northwestern’s investigational new drug (IND) application and data generated from the clinical trial, as well as commercial development rights for stem-cell based products loaded with adenovirus. NNV is composed of an immortalized neural stem cell (NSC) line loaded with an engineered oncolytic adenovirus.

"Calidi’s continued collaboration with Dr. Lesniak has been critical to the development and clinical success of our NeuroNova platform," said Allan J. Camaisa, Chairman and CEO of Calidi Biotherapeutics.

Scheduled for Sunday, November 7, Dr. Lesniak’s presentation will occur during Scientific Session 9: Clinical Trials 3 of the IOVC. Hosted by the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper), the conference spans three days, with presentations from credentialed professionals in the following categories: Novel Payloads and Mechanisms of Action, Novel Combinations and Mechanisms of Action, Novel Platforms, and Clinical Trials. A full program schedule and complete list of invited speakers are available at asgct.org/events/iovc.