1stOncology™: Cancer Intelligence Service – Page 11655 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Vedanta Biosciences Announces Initiation of First-in-Patient Study of Immuno-Oncology Candidate VE800 In Combination with Bristol-Myers Squibb’s Opdivo® (Nivolumab)

On December 10, 2019 Vedanta Biosciences, Inc. (Vedanta Biosciences, Vedanta or the Company), a clinical-stage biopharmaceutical company developing a new category of therapies for immune-mediated diseases based on defined bacterial consortia, reported the initiation of a first-in-patient clinical study of VE800 in combination with Bristol-Myers Squibb’s programmed death-1 (PD-1) immune checkpoint inhibitor Opdivo (nivolumab) in patients with select types of advanced or metastatic cancer (Press release, Vedanta Biosciences, DEC 10, 2019, View Source [SID1234552202]). Vedanta also announced the formation of its Immuno-Oncology Scientific Advisory Board (SAB), which is comprised of experts in immunology, immuno-oncology and the microbiome, to support the planned clinical development of VE800.

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 study, which is being conducted at clinical centers in the United States, will evaluate the safety and tolerability and clinical activity of VE800 in combination with Opdivo, as measured by the confirmed overall response rate, in addition to other parameters. The open-label, non-randomized study will target enrollment of over 100 patients diagnosed with advanced or metastatic melanoma, gastric/gastroesophageal junction adenocarcinoma, or microsatellite-stable colorectal cancer. Eligible patients will receive daily VE800 dosing in combination with Opdivo. Topline results are anticipated in 2021.

"Despite unprecedented global investment in checkpoint inhibitors, there is still a major need for differentiated approaches to further enhance and expand responses in cancer," said Bernat Olle, Ph.D., co-founder and chief executive officer of Vedanta Biosciences. "The role the gut microbiota plays in influencing responses to immunotherapies has been ignored by previous approaches, so we are excited about the potential of microbiome modulation to open up an entirely new approach to cancer therapy."

VE800 is made up of 11 commensal bacterial strains that act in concert to activate cytotoxic CD8+ T cells, which are the vanguard of the immune system’s response to tumors and thus a key driver of effective immunotherapies. In preclinical studies, VE800 has been shown to enhance the ability of these T cells to infiltrate tumors, thereby promoting suppression of tumor growth and potentially enhancing survival. Preclinical data also suggest that VE800 may enhance the effects of checkpoint inhibitors.

Foundational work demonstrating VE800’s novel anti-tumor activity and cooperatively potentiated responses to checkpoint inhibitor therapies and various immune challenges was published in Nature by Vedanta and its scientific co-founder Kenya Honda, M.D., Ph.D., of Keio University School of Medicine. The research also showed that mice colonized with VE800 demonstrated enhanced therapeutic efficacy in a range of tumor models when VE800 was administered in conjunction with PD-1 or CTLA4 immune checkpoint inhibitors.

"The ability of bacterial consortia to mediate immune activity, including potential anti-cancer activity, is an exciting area for investigation in indications with some of the highest unmet medical need," said Hassane M. Zarour, M.D., co-leader of the Cancer Immunology and Immunotherapy Program of the Hillman Cancer Center, University of Pittsburgh, and a member of Vedanta’s newly formed Immuno-Oncology SAB. "We see enormous potential for this class of drugs to improve cancer patients’ outcomes."

Vedanta’s newly announced Immuno-Oncology SAB will work closely with the Company’s scientific co-founders and leadership to further support the clinical development of VE800. The SAB includes:

Antoni Ribas, M.D., Ph.D.is a leading translational and clinical researcher in immuno-oncology with a focus on malignant melanoma. He is a professor of medicine, surgery and molecular and medical pharmacology at the University of California Los Angeles (UCLA), director of the tumor immunology program at the Jonsson Comprehensive Cancer Center, director of the Parker Institute for Cancer Immunotherapy Center at UCLA, chair of the Melanoma Committee at SWOG and president-elect 2019-2020 of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).
Josep Tabernero, M.D., Ph.D. is a researcher focused on gastrointestinal cancers and cancer genetics. At Vall D’Hebron Institute of Oncology (VHIO), he is director of clinical research, co-director of the research unit for molecular therapy of cancer, head of the gastrointestinal and endocrine tumors group, and head of the medical oncology department of Vall d’Hebron University Hospital. He is also president of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper).
Hassane Zarour, M.D. is a researcher with expertise in melanoma and skin lesions, immunotherapy and cancer vaccines. At the University of Pittsburgh Medical Center, he is a professor of medicine, immunology and dermatology, co-leader of the melanoma program and the James W. and Frances G. McGlothlin chair in melanoma immunotherapy research.
Diwakar Davar, MBBS, M.Sc. is a leader in microbiome science and using the microbiome to treat melanoma. He is an assistant professor of medicine at the University of Pittsburgh Medical Center.
Bertrand Routy, M.D., Ph.D. is recognized as one of the first researchers to demonstrate the negative impact of antibiotics and the microbiome on the efficacy of checkpoint inhibitor therapy. He is an assistant professor of hematology-oncology and director of the laboratory of immunotherapy / oncomicrobiome at the Centre hospitalier de l’Université de Montréal (CHUM).
Dan Littman, M.D., Ph.D. is a scientific co-founder of Vedanta and a leader in T cell biology, including differentiation and lineage specification. He is the Helen L. and Martin S. Kimmel professor of molecular immunology and pathology and professor in the department of microbiology at the Skirball Institute of Biomolecular Medicine at New York University Langone School of Medicine.
Sasha Rudensky, Ph.D. is a scientific co-founder of Vedanta and a leader in molecular mechanisms of CD4 T cell differentiation, particularly regulatory T cells. He is chair of the immunology program at Sloan Kettering Institute (SKI) and director of the Ludwig Center at Memorial Sloan Kettering (MSK).
About VE800

VE800 is Vedanta Biosciences’ proprietary, orally administered immuno-oncology product candidate. It is produced from pure, non-pathogenic clonal bacterial cell banks, which yield a standardized drug product in powdered form. VE800 consists of a rationally-defined bacterial consortium of 11 commensal strains that, acting in concert, activate cytotoxic CD8+ T cells, a type of white blood cell that is the predominant effector in cancer immunotherapy. In preclinical studies, VE800 has been shown to enhance the ability of these T cells to infiltrate tumors, thereby promoting suppression of tumor growth and enhancing survival. Preclinical data also suggest that VE800 may enhance the effects of checkpoint inhibitors. Vedanta is evaluating VE800 as a potential treatment for patients with advanced or metastatic cancers.

Geron Reports Two Poster Presentations at American Society of Hematology Annual Meeting

On December 10, 2019 Geron Corporation (Nasdaq: GERN) reported that two posters related to imetelstat, the Company’s first-in-class telomerase inhibitor, were presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida on December 8 and 9 (Press release, Geron, DEC 10, 2019, View Source [SID1234552199]). Both posters are available on Geron’s website at www.geron.com/r-d/publications.

Trials in Progress Poster Presentation

Title: IMerge: A Study to Evaluate Imetelstat (GRN163L) in Transfusion-Dependent Subjects with IPSS Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) That Is Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment (Abstract #4248)

The poster described key aspects of the IMerge Phase 2/3 clinical trial, including: the trial design; patient eligibility criteria; primary, secondary and exploratory endpoints; and the status of the trial. The poster also included a summary of previously presented data from the Phase 2 portion of the IMerge trial.

IMerge is an ongoing global two-part Phase 2/3 clinical trial of imetelstat in red blood cell (RBC) transfusion dependent patients with Low or Intermediate-1 risk, or lower risk myelodysplastic syndromes (MDS), who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint for the IMerge Phase 2/3 clinical trial is 8-week RBC transfusion independence (TI), which is defined as the proportion of patients achieving transfusion independence during any consecutive eight weeks since entry into the trial. Key secondary endpoints include the rate of transfusion independence lasting at least 24 weeks, or 24-week TI rate, durability of transfusion independence and the amount and relative change in transfusions.

IMerge Phase 3 Trial Now Enrolling

The IMerge Phase 3 is planned to enroll approximately 170 patients in a randomized, double-blind, placebo-controlled clinical trial. The trial will enroll non-del(5q) lower risk MDS patients who are naïve to treatment with hypomethylating agents (HMAs) and lenalidomide. The primary and secondary endpoints remain the same as the Phase 2 portion of the trial. Approximately 90 sites are planned to participate in 12 countries across North America, Europe, Middle East and Asia. Enrollment opened in August 2019, and the first patient was dosed in October 2019.

To learn more about the IMerge Phase 3 clinical trial and whether the study is enrolling patients in your area, please visit www.clinicaltrials.gov (NCT02598661).

IMerge Phase 2 Data Summary

Imetelstat treatment showed meaningful and durable transfusion independence in 38 non-del(5q) lower risk MDS patients who were naïve to HMAs and lenalidomide.
42% (16/38) of patients achieved ≥8-week RBC-TI
29% (11/38) of patients achieved ≥24-week RBC-TI
Median duration of TI was 85.9 weeks (range: 8.0-140.9)
68% (26/38) of patients achieved HI-E, or improvement in red blood cell count, as measured by either transfusion reduction or a rise in hemoglobin:
All 26 patients had a reduction of at least four RBC units over eight weeks compared with prior transfusion burden
12 patients had a hemoglobin increase of at least 1.5 g/dL lasting at least eight weeks
Mean relative reduction in transfusion burden from baseline was 68%
Transfusion independence was observed across different MDS patient subgroups.
Biomarker data suggested potential impact on malignant clone and disease modification by imetelstat treatment.
No new safety signals were identified. Reversible cytopenias were the most frequent adverse events.
Non-Clinical Data Poster Presentation

Title: Combination Treatment with Imetelstat, a Telomerase Inhibitor, and Ruxolitinib Depletes Myelofibrosis Hematopoietic Stem Cells and Progenitor Cells (Abstract #2963)

This poster presentation described results from early, nonclinical experiments on the potential effect of combining imetelstat and ruxolitinib on malignant myelofibrosis (MF) cells. The experiments explored the hypothesis that, due to different mechanisms of action, a combination of imetelstat and ruxolitinib might create a treatment regimen for MF that could be more efficacious than using either drug alone in reducing both malignant progenitor and stem cells. Ruxolitinib is a janus kinase (JAK) inhibitor that inhibits proliferation of malignant progenitor cells without eliminating malignant stem cells. Imetelstat is a telomerase inhibitor that selectively depletes malignant progenitor and stem cells.

In the experiments, the sequential treatment of ruxolitinib followed by imetelstat had additive inhibitory activity resulting in greater reductions in both malignant progenitor and stem cells when compared to simultaneous treatment or either drug alone. Furthermore, the sequential treatment regimen did not affect normal hematopoietic progenitor and stem cells. As stated in the poster, these non-clinical findings suggest that sequential treatment of ruxolitinib followed by imetelstat represents a potentially effective treatment that may eliminate both malignant MF progenitor and stem cells.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat consist of IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMbark, a Phase 2 trial in Intermediate-2 or High-risk myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

OMEROS TO PRESENT GPR174 DATA AT THE EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY 2019 IMMUNO-ONCOLOGY CONGRESS IN GENEVA

On December 10, 2019 Omeros Corporation (Nasdaq: OMER) reported an upcoming presentation directed to its novel cancer immunotherapy target GPR174 at the European Society for Medical Oncology 2019 Immuno-Oncology Congress, which is being held December 11-14, 2019 in Geneva, Switzerland (Press release, Omeros, DEC 10, 2019, View Source [SID1234552198]).

In addition to previously presented ex vivo human and in vivo animal studies, the presentation will include new findings from human T-cells demonstrating that GPR174 inhibition results in downregulation of checkpoint and tumor promoting factors.

The poster (#108P) will be presented on December 12, 2019, at 12:15 PM local time by Marc Gavin, Ph.D., Omeros’ Director of Immunology.

SCYNEXIS Announces Pricing of $35 Million Public Offering of Common Stock and Warrants

On December 10, 2019 SCYNEXIS, Inc. (NASDAQ: SCYX) reported the pricing of its previously announced underwritten public offering of 38,888,889 shares of common stock and warrants to purchase up to 38,888,889 shares of common stock (Press release, Scynexis, DEC 10, 2019, View Source [SID1234552197]). Each share of common stock and warrant to purchase one share of common stock are being sold at a combined public offering price of $0.90 per share and accompanying warrant. The gross proceeds to SCYNEXIS from this offering are expected to be approximately $35 million, before deducting underwriting discounts and commissions and other estimated offering expenses, and excluding the exercise of any warrants. All of the shares of common stock and warrants are being offered by SCYNEXIS.

H.C. Wainwright & Co. is acting as sole book-running manager for the offering.

The warrants will have an exercise price of $1.10 per share and exercise period commencing immediately upon issuance and an expiration date of the earlier of (i) such date that is six months after SCYNEXIS publicly announces the approval from the U.S. Food and Drug Administration for ibrexafungerp for the treatment of vulvovaginal candidiasis and (ii) June 12, 2023. There is no established public trading market for the warrants, and SCYNEXIS does not expect a market to develop.

In addition, SCYNEXIS has granted the underwriters a 30-day option to purchase up to an additional 5,833,333 shares of common stock and/or warrants to purchase up to 5,833,333 shares of common stock, at the public offering price, less the underwriting discounts and commissions. The offering is expected to close on or about December 12, 2019, subject to customary closing conditions. A shelf registration statement relating to the securities being sold in this offering was filed with the U.S. Securities and Exchange Commission (SEC) on August 31, 2018, and was declared effective on September 14, 2018. The offering is being made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to the offering were filed with the SEC and a final prospectus supplement and accompanying prospectus will be filed with the SEC and will be available for free on the SEC’s website located at View Source When available, electronic copies of the final prospectus supplement and accompanying prospectus relating to the public offering may be obtained by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, or by telephone at (646) 975-6996, or by email to [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Celyad Presents Update on r/r AML and MDS Program at 61st ASH Annual Meeting

On December 10, 2019 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell therapies, reported updates to the company’s autologous NKG2D-based CAR-T development program for the treatment of relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the American Society of Hematology (ASH) (Free ASH Whitepaper) 61st Annual Meeting, which is being held from December 7-10, 2019 in Orlando, Florida (Press release, Celyad, DEC 10, 2019, View Source [SID1234552196]).

Filippo Petti, CEO of Celyad, commented, "Over the past few months we have worked diligently to transition our proprietary OptimAb manufacturing process to become the cornerstone of our autologous CAR-T program for the treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes. We are encouraged by the body of data generated to date by our lead autologous candidate CYAD-01 for the treatment of AML and MDS, especially given its tolerability profile and anti-leukemic activity."

"We are excited to further evaluate our NKG2D-based CAR-T approach using our OptimAb manufacturing process, which generates a higher frequency of less differentiated CAR-T cells that exhibit enhanced anti-tumor activity in preclinical studies. Overall, we believe the process gives us the best opportunity for success across both autologous product candidates, CYAD-01 and CYAD-02. Along with our ongoing DEPLETHINK trial, the key next steps for our broad r/r AML and MDS program include the expansion of the THINK trial and initiation of the CYCLE-1 trial as we look to establish NKG2D as an important target for the treatment of difficult-to-treat malignancies", continued Mr. Petti.

CYAD-01 THINK Phase 1 Trial

Sixteen patients have been enrolled to date in the trial evaluating CYAD-01 administered as a multiple injection with a biweekly schedule and an additional nine patients have been enrolled in the dose dense (weekly) schedule in the dose escalation segment of the trial
CYAD-01 without preconditioning chemotherapy was generally reported to be well-tolerated, with 11 out of 25 patients experiencing grade 3/4 treatment-related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 13 patients, with four grade 3 and two grade 4 events, which showed rapid resolution following the appropriate treatment, including tocilizumab. Two dose-limiting toxicities were reported at dose level 3 (3 billion cells per infusion), including one CRS grade 4 (biweekly) and one CRS grade 3 (dose dense schedule). No treatment-related neurotoxicity AEs were reported
Overall, eight patients out of 15 evaluable patients treated with CYAD-01 produced with the prior manufacturing process demonstrated anti-leukemic activity. Five out of the eight patients exhibited an objective response. In addition, one patient is exhibiting disease stabilization of over three months
Patients treated within the CYAD-01 dose-dense (weekly) schedule cohorts of the trial did not demonstrate an improvement in clinical outcome as compared to patients treated with the biweekly dosing schedule. However, patients enrolled in the dose-dense schedule cohorts appeared to have greater bone marrow blasts infiltration and to be more pancytopenic at baseline compared to patients enrolled in the biweekly dose escalation segment of the trial
Most of the anti-leukemic activity observed in the trial, except for the two patients who bridged to an allogeneic human stem cell transplant, experienced a short durability of response
To date, anti-leukemic activity appears predominantly observed in patients initially diagnosed with non-adverse (ELN 2017, AML) or non-very high (IPSS-R, MDS) risk stratification categories. Additional patients are needed in the trial to better assess the observation
Company plans to progress to the expansion segment of the THINK trial to further evaluate CYAD-01 produced with the OptimAb manufacturing process. Enrollment in the expansion segment of the trial is expected to begin in first quarter 2020 with preliminary data anticipated by the end of first half 2020
CYAD-01 DEPLETHINK Phase 1 Trial

Nine patients have been enrolled in the trial evaluating CYAD-01 produced with the prior mAb manufacturing process following preconditioning chemotherapy cyclophosphamide and fludarabine, or CyFlu, at the first two dose levels of the dose escalation segment of the trial
CYAD-01 produced with the mAb manufacturing process was generally reported to be well-tolerated following preconditioning chemotherapy. At the first CYAD-01 infusion of the consolidation cycle (3 billion cells per infusion), one patient experienced both grade 4 cytokine release syndrome (CRS) and grade 3 CAR-T cell-related encephalopathy and another patient experienced grade 3 CRS. Both patients recovered following the appropriate treatment, including tocilizumab
Preconditioning chemotherapy led to improved, dose-dependent engraftment of CYAD-01 cells as compared to cells infused with no preconditioning
To date, no objective response has been observed at the first two dose levels of the trial in patients treated with CYAD-01 produced with the mAb manufacturing process
In September 2019, the company announced the successful administration of CYAD-01 produced with the OptimAb manufacturing process to a patient enrolled in cohort 3 (300 million cells per infusion) of the trial
Enrollment in the trial is ongoing with plans to dose escalate up to one billion cells per infusion in cohort 4. Preliminary data evaluating CYAD-01 produced with the OptimAb manufacturing process from cohorts 3 and 4 are expected by the end of first half 2020
CYAD-02 CYCLE-1 Phase 1 Trial

In November 2019, the company initiated the dose-escalation Phase 1 CYCLE-1 trial (NCT04167696), which will evaluate the safety and clinical activity of the next-generation, autologous NKG2D-based CAR-T candidate CYAD-02, produced with the OptimAb manufacturing process following preconditioning chemotherapy CyFlu in patients with r/r AML and MDS
CYAD-02 incorporates shRNA SMARTvector technology licensed from Horizon Discovery to target the NKG2D ligands MICA and MICB. shRNA-mediated knockdown of MICA and MICB expression on NKG2D CAR-T cells has been shown to enhance in vitro expansion of the CAR-T cells and enhanced engraftment and persistence in preclinical models as compared to CYAD-01 produced with the mAb process
Enrollment in the CYCLE-1 trial is expected to begin in early 2020 with preliminary data anticipated during second half 2020
About THINK Phase 1 Trial

The THINK trial (NCT03018405) is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of multiple CYAD-01 administrations without prior preconditioning. The dose escalation segment of the trial evaluated three dose levels (300 million, 1 billion and 3 billion cells per infusion) of one cycle of three CYAD-01 administrations with two-week intervals. In 2018, the THINK trial was amended to add two cohorts to assess a more frequent dosing schedule of CYAD-01 for the treatment of r/r AML. The cohorts will evaluate six injections of CYAD-01 without preconditioning over two months of administration. The first cycle includes three infusions of CYAD-01 separated by one-week intervals. The second cycle includes three infusions of CYAD-01 separated by two-week intervals. Patients will either receive 1 billion cells per infusion (Cohort 10) or 3 billion cells per infusion (Cohort 11). The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

About DEPLETHINK Phase 1 Trial

In October 2018, Celyad initiated the DEPLETHINK Phase 1 trial (NCT03466320). The open-label, dose-escalation trial is designed to evaluate a single infusion of CYAD-01 following treatment with the standard preconditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu. The trial includes two different intervals between lymphodepletion and administration of CYAD-01. In addition, the trial is evaluating three dose levels of CYAD-01 including 100 million, 300 million and 1 billion cells per infusion, respectively. The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

About OptimAb Manufacturing Process

Celyad’s proprietary OptimAb manufacturing process utilizes a shortened cell culture and incorporates a selective PI3K inhibitor. This results in a product that is enriched for T cells with a memory-like phenotype. Preclinical data demonstrate that NKG2D-based CAR-T cell therapies produced using the OptimAb manufacturing process drive improved anti-tumor activity in an aggressive AML model compared to alternative manufacturing process.