On December 13, 2021 PharmaMar (MSE:PHM) and partner Jazz Pharmaceuticals plc (Nasdaq:JAZZ) reported the initiation of a confirmatory Phase III clinical trial, LAGOON, evaluating Zepzelca (lurbinectedin) for the treatment of patients with relapsed Small Cell Lung Cancer (SCLC) (Press release, PharmaMar, DEC 13, 2021, View Source [SID1234596896]). The trial will measure Overall Survival (OS) as primary endpoint and Progression-Free Survival (PFS) as one of the secondary endpoints of lurbinectedin monotherapy or lurbinectedin in combination with irinotecan, compared with investigator’s choice of topotecan or irinotecan, in patients with SCLC whose disease has progressed following prior platinum-containing chemotherapy with or without anti-PD-1 or anti-PD-L1 agents.

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"We are very excited about this trial, which is designed to reinforce lurbinectedin as a second-line treatment of choice in the U.S. and has the potential to bring our treatment to European patients,"

Said Ali Zeaiter, M.D., director of Clinical Development, PharmaMar Oncology Business Unit.

"There has been a strong clinical demand for lurbinectedin following the FDA’s accelerated approval, which demonstrates that this important therapy is filling a significant unmet need for the metastatic small cell lung cancer community,"

Said Rob Iannone, M.D., M.S.C.E., executive vice president, research and development and chief medical officer at Jazz Pharmaceuticals.

"We are committed to working with PharmaMar and the FDA to further demonstrate the clinical benefit of lurbinectedin and support conversion to full regulatory approval in the U.S."

LAGOON is a Phase III, randomized (1:1:1), multicenter, open-label clinical trial with three arms: one arm to receive lurbinectedin 3.2 mg/m2 as monotherapy (the approved dose in the U.S.), the second arm to receive lurbinectedin 2.0 mg/m2 in combination with irinotecan 75 mg/m2 and the third arm to receive topotecan or irinotecan based on the investigators’ choice. The trial will be conducted in patients with SCLC, whose disease has progressed following prior platinum-containing chemotherapy with or without anti-PD-1 or anti-PD-L1 agents. LAGOON is expected to enroll 705 patients from more than 100 sites mainly in North America and Europe.

The FDA approved lurbinectedin under accelerated approval in June 2020 for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The approval is based on Overall Response Rate (ORR) and Duration of Response (DoR) demonstrated in an open-label, monotherapy clinical study. If successful, LAGOON will serve as the confirmatory trial for lurbinectedin to secure full approval in the U.S. LAGOON will also be used as a registrational trial with the European Medicines Agency (EMA) to obtain marketing authorization in Europe. Jazz Pharmaceuticals holds the commercial rights for lurbinectedin in North America.

In 2021, lurbinectedin received marketing authorization in the United Arab Emirates, Canada, Australia and Singapore. Additional marketing authorizations are expected in 2022 and beyond.

On December 13, 2021 GlycoMimetics, Inc. (Nasdaq: GLYC) reported this week at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta presented two posters providing support for targeting both CXCR4 and E-selectin with GMI-1359, the Company’s dual antagonist of CXCR4 and E-selectin, as a novel treatment strategy for patients with AML (Press release, GlycoMimetics, DEC 13, 2021, View Source [SID1234596922]).

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"Both posters demonstrate the potential value of blocking extrinsic factors of AML drug resistance in the bone marrow microenvironment with our dual-function antagonist GMI-1359. The work done at MD Anderson specifically demonstrates that by disrupting tumor-stromal interactions within the bone marrow, as measured by increased in vivo cell motility, GMI-1359 significantly enhances/restores the antileukemic activity of venetoclax/HMA and FLT3 inhibitors. Importantly, GMI-1359 also protects the normal hematopoietic stem cells and the bone marrow compartment from detrimental toxic side effects from chemotherapy as experienced with venetoclax/HMA treatments. These data support our belief that targeting extrinsic factors of chemoresistance with GMI-1359 can increase not only the efficacy but also the safety of conventional AML therapy," said John Magnani, PhD, GlycoMimetics’ Chief Scientific Officer.

The first poster (#1171) — presented December 11 — describes the unexpected activities of FLT-3 inhibitors such as quizartinib and sorafenib in upregulating the expression of E-selectin ligands (sialyl Lex) and CXCR4, thereby increasing adhesion to protective niches in the bone marrow microenvironment and inducing chemoresistance. Using cells from a relapsed patient treated with a FLT-3 inhibitor in a murine model, the addition of GMI-1359, a dual antagonist of E-selectin and CXCR4, to quizartinib broke chemoresistance, led to a dramatic reduction in leukemic burden and a doubling of median survival time from 79 to 158 days (p<0.0001).

The second poster (#3348), presented today contains data demonstrating that in a patient derived xenograft model, both uproleselan and GMI-1359 increased the efficacy and extended median survival time in engrafted mice treated with venetoclax/HMA from 74 days to 90 and 91 days, respectively. In these studies, the inclusion of uproleselan or GMI-1359 in combination with venetoclax/HMA further significantly decreased both the leukemic blast and leukemic stem cell burden beyond that obtained with venetoclax/HMA alone. Coincident with these studies data in the poster also demonstrate through intravital microscopy that GMI-1359 reduced adhesion and stimulated mobility of leukemic stem cells within the bone marrow microenvironment suggesting the disruption of both the E-selectin/E-selectin ligand and the CXCR4/CXCL12 axes. In addition, the poster includes evidence that uproleselan and GMI-1359 preserve the nontumor bone marrow component cells from venetoclax/HMA detrimental effects through the upregulation of survival signaling cascades, while protecting the hematopoietic stem cells and the bone marrow components from this treatment.

The accepted abstracts are available online through the ASH (Free ASH Whitepaper) meeting website. Both posters are available on the Company’s website, www.glycomimetics.com under the PUBLICATIONS tab.

About GMI-1359

GMI-1359 is designed to simultaneously inhibit both E-selectin and CXCR4 — both adhesion molecules involved in tumor trafficking and metastatic spread. Preclinical studies indicate that targeting both E-selectin and CXCR4 with a single compound could improve efficacy in the treatment of cancers that involve the bone marrow such as AML and multiple myeloma or in solid tumors that metastasize to the bone, such as prostate cancer and breast cancer, as well as in osteosarcoma, a rare pediatric tumor. GMI-1359 has received Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA for the treatment of osteosarcoma, a rare cancer affecting about 900 adolescents a year in the United States.

About Uproleselan

Discovered and developed by GlycoMimetics, uproleselan is an investigational, first-in-class, targeted inhibitor of E-selectin. Uproleselan (yoo’ pro le’ sel an), currently in a comprehensive Phase 3 development program in AML, has received Breakthrough Therapy Designation from the U.S. FDA and from the Chinese National Medical Products Administration for the treatment of adult AML patients with relapsed or refractory disease. Uproleselan is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment.

On December 13, 2021 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for cancer and other serious diseases, reported that two-year follow-up data for GDA-201, the company’s lead candidate in its NAM-enabled NK cell therapy pipeline, will be presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, being held in Atlanta, Georgia (Press release, Gamida Cell, DEC 13, 2021, View Source [SID1234596970]). Additionally, for patients who participated in the phase 3 trial of omidubicel, the company will be presenting a poster of an analysis of resource utilization data from the first 100 days after bone marrow transplant.

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The poster titled "GDA-201, A Novel Metabolically Enhanced Allogeneic Natural Killer (NK) Cell Product Yields High Remission Rates in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma (NHL): 2-year survival and correlation with cytokine IL7" includes longer term follow-up from the phase 1, investigator-led study of GDA-201 in combination with rituximab (NCT03019666) in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and reports on 2-year outcomes and cytokine biomarkers associated with survival. The data demonstrated a median duration of response of 16 months (range 5- 36 months), an overall survival at 2 years of 78% (95% CI, 51%–91%) and a safety profile similar to that reported previously.

"We are excited to share this compelling two-year data from our investigator-led study of GDA-201 which demonstrate an extended duration of response in patients with NHL," said Julian Adams, Ph.D., Chief Executive Officer, of Gamida Cell. "The durable response in this patient group provides strong support as we work to progress GDA-201 through the development process for patients in need."

Gamida Cell will also present a poster related to its omidubicel program titled "Hospitalization and Healthcare Resource Use of Omidubicel Vs Cord Blood Transplantation for Hematological Malignancies in a Global Randomized Phase III Clinical Trial," which includes an analysis of resource utilization data from the first 100 days after transplant for 108 patients in the phase 3 trial showing that the omidubicel-treated patients had significantly shorter durations of hospitalization, intensive care unit stays, consultant visits, procedures, and transfusions than the control arm. These data provide further evidence of the clinical benefit associated with the more rapid hematopoietic recovery in patients treated with omidubicel and the corresponding reduction in healthcare resource utilization.

"This analysis clearly demonstrates the potential of omidubicel to significantly shorten a patient’s hospital length of stay, reduce time in ICU settings and decrease usage of healthcare resources, likely resulting in lower overall costs to the healthcare system," said Ronit Simantov, M.D., Chief Medical Officer of Gamida Cell. "These findings are particularly important as they demonstrate the impact of omidubicel on the experience for patients during the critical post-transplant period."

Both posters will be available today, Monday, December 13, 2021, 6:00-8:00 p.m. ET, during the ASH (Free ASH Whitepaper) Annual Meeting and Exposition.

About GDA-201

Gamida Cell applied the capabilities of its nicotinamide (NAM)-enabled cell expansion technology to develop GDA-201, an innate NK cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard of care antibody therapies. GDA-201, the lead candidate in the NAM-enabled NK cell pipeline, has demonstrated promising initial clinical trial results. GDA-201 addresses key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs. Furthermore, GDA-201 improves antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. For more information about GDA-201, please visit View Source

GDA-201 is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

About Omidubicel

Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with blood cancers. Omidubicel is the first bone marrow transplant graft to receive Breakthrough Therapy Designation from the U.S. FDA and has also received Orphan Drug Designation in the U.S. and EU. For more information about omidubicel, please visit View Source

Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.

On December 13, 2021 Novartis reported the introduction of T-Charge, the company’s next-generation CAR-T platform that will serve as the foundation for various new investigational CAR-T cell therapies in the Novartis pipeline (Press release, Novartis, DEC 13, 2021, View Source [SID1234596991]). At the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) 2021, Novartis will present early clinical data from ongoing Phase I clinical trials with YTB323 (anti-CD19) and PHE885 (anti-BCMA), the first Novartis CAR-T cell therapies developed using this platform. Notably, initial efficacy data show a complete response rate of 73% (95% CI: 44.9, 92.2) at month three for the 15 patients with diffuse large B-cell lymphoma (DLBCL) who received dose level two of YTB3231. For the 11 patients with multiple myeloma who received the two highest doses of PHE885, the best overall response was 100%2.

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The T-Charge platform preserves T cell stemness, the ability to self-renew and mature, which results in a product containing greater proliferative potential and fewer exhausted T cells3,4. With T-Charge, CAR-T cell expansion occurs primarily within a patient’s body (in-vivo), eliminating the need for an extended culture time outside of the body (ex-vivo)3,4. These unique characteristics of the T-Charge platform may lead to better and more durable responses, improved long-term outcomes and a reduced risk of severe adverse events1-4.

"With T-Charge, we aim to build on the vast knowledge gleaned from early investment in CAR-T research and trials. Our ambition now is to go beyond incremental advances, to further reimagine CAR-T cell therapy and give patients a higher likelihood of durable responses with the ultimate potential for a cure," said Jay Bradner, President of the Novartis Institutes for BioMedical Research. "We are encouraged by these promising early clinical data from the first CAR-T cell therapies produced using the T-Charge platform as we look to accelerate their development and delivery to patients."

Phase I YTB323 clinical study1
YTB323, an investigational, autologous CD19-directed CAR-T cell therapy developed using the T-Charge platform, showed promising results in the diffuse large B-cell lymphoma arm of a first-in-human, multicenter, Phase I dose-escalation study. Patients received a single treatment of YTB323 at two dose levels (DL). The median administered doses were 2.5×106 CAR+ cells (DL1; n=4) and 12.5×106 CAR+ cells (DL2; n=16). Of the 15 patients who received YTB323 treatment at DL2 at least three months prior to the data cut-off, the complete response (CR) rate was 73% (95% CI: 44.9, 92.2), including two patients who were in CR prior to treatment with YTB323.

For the 20 patients evaluable for safety, there were no new safety signals beyond those previously known to be related to CD19-directed CAR-T cell therapy. All AEs were reported regardless of the study drug relationship. Six patients experienced CRS including five of grade 1/2 and one of grade 4. Five patients had neurological adverse reactions (AR), of which two events were considered serious (both at DL2; one experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and the other experienced grade 2 seizure that resulted in a grade 3 ICANS). Recruitment for this trial is ongoing. These data will be presented in an oral session at the ASH (Free ASH Whitepaper) annual meeting (Abstract #740; Monday, December 13, 3:00 PM EST).

"The introduction of CAR-T cell therapy led to unprecedented efficacy results for patients facing limited treatment options and a poor prognosis. Unfortunately, some patients with late-stage B-cell malignancies relapse or do not respond after initial response when treated with traditional CAR-T cell therapies," said principal investigator Ian W. Flinn, MD, PhD, Director of the Lymphoma Research Program at Sarah Cannon Research Institute in Nashville. "As part of a community of researchers, physicians and patient advocates, I am hopeful about the promise of novel and next-generation CAR-T cell therapies."

Phase I PHE885 clinical study2
PHE885, an investigational, autologous BCMA-directed CAR-T cell therapy developed using the T-Charge platform, demonstrated promising results in patients with relapsed or refractory multiple myeloma in a first-in-human Phase I, multicenter, dose-escalation study. Fifteen patients were evaluated for efficacy and safety and the fixed doses received were 2.5×106 (n=4), 5×106 (n=10) and 14.3×106 CAR-T cells (n=1). Although the follow-up period was brief, PHE885 shows encouraging initial clinical activity with a best overall response of 100% for patients receiving the 5×106 or 14.3×106 CAR-T cell dose, with responses deepening over time. With a median follow-up of 3.5 months, eight of 15 patients had ongoing responses at the time of data cutoff. Of the evaluable patients at three months post administration, 34% (2/6) were MRD-negative by next-generation sequencing (NGS) at 10-6; 43% (3/7) were MRD-negative at 10-5.

All patients experienced CRS with two patients experiencing grade ≥3 CRS. No patients experienced grade 4 or 5 CRS. All neurotoxicity events (n=4) were nonserious, grade 1-2, reversible, and temporally associated with CRS. Recruitment for this trial is ongoing. These data will be presented in a poster presentation session at the ASH (Free ASH Whitepaper) annual meeting (Abstract #3864; Monday, December 13, 6:00 PM EST).

Results from pre-clinical studies of YTB323 and PHE885 that served as the scientific rationale to initiate these Phase I clinical trials will also be presented at the meeting (Abstracts #2848 and #2770).

About T-Charge1-4
T-Charge is a next-generation CAR-T platform, innovated at the Novartis Institutes for BioMedical Research (NIBR), that will serve as the foundation for various new investigational CAR-T cell therapies in the Novartis pipeline. By implementing the T-Charge platform, we aim to revolutionize CAR-T cell therapy with new products that have the potential to offer patients a higher likelihood of better and more durable responses, improved long-term outcomes and a reduced risk of severe adverse events. The T-Charge platform preserves T cell stemness (T cell ability to self-renew and mature), an important T cell characteristic closely tied to its therapeutic potential, which results in a product containing greater proliferative potential and fewer exhausted T cells. With T-Charge, CAR-T cell expansion occurs primarily within the patient’s body (in-vivo), eliminating the need for an extended culture time outside of the body (ex-vivo). The T-Charge platform, which implements important process efficiencies, will be rapid, compared with traditional CAR-T, and reliable, through simplified processes and streamlined quality control. Multiple CAR-T therapies, including YTB323 and PHE885, are being developed using the Novartis T-Charge platform.

About Novartis commitment to Oncology Cell Therapy
Novartis has a mission to reimagine medicine by bringing curative cell therapies to patients worldwide. Novartis has a deep CAR-T pipeline and ongoing investment in manufacturing and supply chain process improvements. With active research underway to broaden the impact of cell and gene therapy in oncology, Novartis is going deeper in hematological malignancies, reaching patients with other cancer types and evaluating next-generation CAR-T cell therapies that focus on new targets and utilize new platforms.

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials.

On December 13, 2021 Akoya Biosciences, Inc., (Nasdaq: AKYA), The Spatial Biology Company, and PathAI, a global leader in artificial intelligence (AI)-powered technology for pathology, reported a collaboration to advance the discovery and validation of novel predictive biomarkers for immunotherapies (Press release, Akoya Biosciences, DEC 13, 2021, View Source [SID1234596906]). The partners will leverage their industry leading capabilities in spatial biology and deep data mining using Phenoptics, Akoya’s high throughput spatial phenotyping platform, and PathAI’s artificial intelligence tools and algorithms to enhance their shared biopharmaceutical partners’ ability to identify patients most likely to respond to drugs in clinical trials.

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Akoya will work with PathAI to create a seamless interface between the Advanced Biopharma Solutions (ABS) service offerings and PathAI’s analytical capabilities to provide a powerful and complete solution for biopharma partners. This partnership and ABS’ recent CLIA certification represent significant milestones in advancing Akoya’s ability to serve the growing demand for spatial biomarkers in clinical trials.

"The combined power of spatial phenotyping and high throughput data sets from Akoya and PathAI’s algorithms can accelerate the discovery of spatial phenotypic signatures in the tumor microenvironment," said Dr. Andy Beck, CEO of PathAI. "This could streamline drug development to identify patients with a high likelihood of responding to immunotherapies."

Discovery and validation of novel biomarkers could have particularly important near-term implications for improving the efficacy rates of immuno-oncology treatments, an area of medicine that is revolutionizing cancer treatment. Spatial biology is a rapidly emerging scientific discipline that enables deeper understanding of cancer immunology by analyzing the spatial architecture of tumor tissue sections and mapping the complex organization and interactions of tumor and immune cells within the tumor microenvironment. These insights streamline drug development, clinical trials, and biomarker discovery, and are currently being applied to immunotherapy research.

"This collaboration takes Akoya’s ABS offering to the next level by providing biopharma partners with a comprehensive offering that integrates the most advanced technologies and know how in the field of spatial biomarkers and digital pathology," said Brian McKelligon, Chief Executive Officer of Akoya Biosciences. "The combination of our Phenoptics platform and PathAI’s AI-powered technology has the potential to transform biomarker use in clinical trials and ultimately impact cancer care."

Dr. Michael Montalto, Chief Scientific Officer of PathAI, will discuss the role of AI in spatial biomarker development at Akoya’s Spatial Day Event on December 15, 2021. Register at this link.