On October 26, 2021 SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported that the independent Data and Safety Monitoring Board (DSMB) for the Phase 1/2 clinical trial SQZ-PBMC-HPV-101 has recommended that the trial advance into the combination stage with checkpoint inhibitors. In June, the company presented initial results from the first three monotherapy cohorts at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting demonstrating that the investigational cell therapy is safe and well-tolerated and can stimulate immune responses in certain patients with advanced or metastatic human papillomavirus positive (HPV16+) tumors (Press release, SQZ Biotech, OCT 26, 2021, View Source [SID1234591976]). Data from the highest dose monotherapy cohort has been accepted for oral presentation at the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress being held December 8-11, 2021.

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"We are encouraged by our initial SQZ-PBMC-HPV-101 Phase 1/2 trial data and pleased to advance the highest dose of our SQZ APC clinical candidate into the combination stage of the trial," said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. "Based on our preclinical studies and available clinical trial data, we believe SQZ APCs could work synergistically with checkpoint inhibitors to provide additional clinical benefit to patients. Our clinical team and trial sites are ready to begin this important phase of the study."

The combination stage of the trial is now open for enrollment and will include checkpoint inhibitors targeting the PD-(L)1 and CTLA-4 pathways. In parallel, the company plans to continue to enroll in the highest dose monotherapy cohort.

The DSMB recommendation and initiation of the combination cohorts will trigger a Roche collaboration agreement milestone payment. The company’s most recently reported cash runway projections anticipated these proceeds.

New data from the monotherapy portion of the SQZ-PBMC-HPV-101 trial will be part of an oral presentation at ESMO (Free ESMO Whitepaper)-IO on December 9 in Geneva, Switzerland. Full presentation details can be found below.

ESMO-IO Presentation Details

Oral Presentation: Thursday, December 9 at 12:10 pm CET
Presentation Number: 48MO
Abstract Title: SQZ-PBMC-HPV-101: Preliminary results of a first-in-human, dose-escalation study of a cell-based vaccine in HLA-A*02+ patients with recurrent, locally advanced, or metastatic HPV16+ solid tumors

Lead Author: Jong Chul Park, MD, Massachusetts General Hospital; Developmental Therapeutics Member, Dana-Farber/Harvard Cancer Center

ESMO-IO will publish full abstracts on their website on Thursday, December 2 at 12:00 pm CET. SQZ will post its oral presentation on the company website on December 9 at 11:00 am CET.

SQZ-PBMC-HPV-101 Trial Design

SQZ-PBMC-HPV is being evaluated in a Phase 1/2 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination stages of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a dose-limiting toxicity (DLT) window of 28 days and the definition of a recommended phase 2 dose. The planned combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors. DLT will be measured over 42 days.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

On October 26, 2021 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported the first project to be developed within beLAB2122, a collaboration between Evotec and Bristol Myers Squibb (Press release, Evotec, OCT 26, 2021, View Source;announcements/press-releases/p/evotec-se-translational-bridge-belab2122-in-collaboration-with-bristol-myers-squibb-identifies-first-project-6110 [SID1234591992]). beLAB2122 aims to bring together leading academic institutions from the Rhine-Main-Neckar region of Germany with the goal of efficiently advancing first-in-class therapeutic options across all therapeutic areas and formats into investable drug discovery and early development projects. After signing the beLAB2122 collaboration agreement in April 2021, the first project to be developed within this academic BRIDGE collaboration has now been nominated.

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Originating in the laboratory of Dr Darjus Tschaharganeh, Group Leader at the German Cancer Research Center ("DKFZ"), Heidelberg, and Professor at Heidelberg University, the project is based on the observation of synthetic lethal interactions in certain cancer types and aims at the development of small molecule inhibitors of a nutrient transporter essential for the survival of these cancer cells.

beLAB2122 will now leverage Evotec’s integrated discovery and development platform to validate and develop the project further. The goal of beLAB2122 is to develop academic projects to value inflection points that allow the formation of new jointly owned spin-off companies.

Dr Thomas Hanke, EVP & Head of Academic Partnerships at Evotec, commented: "We are pleased to further explore the promising approach from the DKFZ and Heidelberg University as the first funded project of beLAB2122. Evotec’s BRIDGE collaborations aim at seamlessly integrating academic innovations into the pharmaceutical value chain and accelerating them to new company formations. We look forward to progressing this and many more interesting academic projects using Evotec’s highly efficient integrated drug discovery & development infrastructure called the ‘Data-driven R&D Autobahn to Cures’. At the same time, we are pleased to receive additional promising applications from scientists working within the beLAB2122 member institutions at the EMBL, the German Cancer Research Center, the Goethe University Frankfurt, Heidelberg University and Tübingen University, and are looking forward to expanding the scope of the project portfolio further."

Dr Darjus Tschaharganeh, Group Leader at the German Cancer Research Center (DKFZ) and Professor at Heidelberg University, added: "We are excited to be chosen as the first beLAB2122 project and to be part of the collaboration bridge. Our project evolved from fundamental basic research and we are now at a point that our results clearly illustrate that pharmacological inhibitors for this target could be very successful for cancer treatment. The beLAB2122 initiative with strong pharmaceutical partners is ideally suited to pursue this project. We are looking forward to a close interaction with Evotec and Bristol Myers Squibb and hope that we can find potent inhibitors for our target in order to get to the next step and hopefully will be able to bring this in the future to the clinics for the benefit of patients."

beLAB2122 is backed by Evotec in collaboration with Bristol Myers Squibb. The total volume of US$ 20 m will allow for several more funding rounds. For more information on beLAB2122, visit www.belab2122.org.

On October 26, 2021 Alkermes plc (Nasdaq: ALKS) reported the initiation of ARTISTRY-7, a global phase 3, open-label, randomized trial evaluating the anti-tumor activity and safety of intravenously administered (IV) nemvaleukin alfa (nemvaleukin), in combination with pembrolizumab, compared to investigator’s choice chemotherapy, in patients with platinum-resistant ovarian cancer. Nemvaleukin, Alkermes’ lead immuno-oncology candidate, is a novel, investigational, engineered interleukin-2 (IL-2) variant immunotherapy (Press release, Alkermes, OCT 26, 2021, View Source [SID1234591943]). As previously announced, ARTISTRY-7 is being conducted in collaboration with MSD (a tradename of Merck & Co., Inc. Kenilworth, NJ, USA), which is providing KEYTRUDA (pembrolizumab) for the study. In addition, Alkermes is working with The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) to conduct the study. The U.S. Food and Drug Administration recently granted Fast Track designation to nemvaleukin in combination with pembrolizumab for the treatment of platinum-resistant ovarian cancer.

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"The initiation of our phase 3 study of nemvaleukin in platinum-resistant ovarian cancer is an important milestone for the nemvaleukin clinical development program and reflects our commitment to focusing on the high unmet need of patients living with difficult-to-treat cancers such as platinum-resistant ovarian cancer," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President of Research & Development at Alkermes. "ARTISTRY-7 is designed to build upon the durable and deepening responses observed in heavily pre-treated patients with platinum-resistant ovarian cancer in the ongoing ARTISTRY-1 study. We look forward to sharing updates from ARTISTRY-7 as the study progresses and as we advance toward potential registration."

ARTISTRY-7 is a global phase 3, open-label, randomized study designed to evaluate the anti-tumor activity and safety of IV nemvaleukin in combination with pembrolizumab compared to investigator’s choice chemotherapy, with additional nemvaleukin and pembrolizumab monotherapy arms, in patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. The primary endpoint of ARTISTRY-7 is progression-free survival as assessed by the investigator, based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Additional endpoints include objective response rate, overall survival, disease control rate, duration of response, time to response, cancer antigen-125 response, pharmacokinetics (PK)/ pharmacodynamics (PD) and safety. The study is expected to enroll approximately 376 patients. Patients will be randomized to one of four treatment arms to receive nemvaleukin and pembrolizumab combination therapy, pembrolizumab monotherapy, nemvaleukin monotherapy, or investigator’s choice chemotherapy.

More information can be found at www.clinicaltrials.gov (NCT05092360, GOG-3063, ENGOT-ov68)

About Nemvaleukin Alfa (nemvaleukin)
Nemvaleukin is an investigational, novel, engineered fusion protein comprised of modified interleukin-2 (IL-2) and the high affinity IL-2 alpha receptor chain, designed to preferentially expand tumor-killing immune cells while avoiding the activation of immunosuppressive cells by selectively binding to the intermediate-affinity IL-2 receptor complex. The selectivity of nemvaleukin is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About the ARTISTRY Clinical Development Program
ARTISTRY is an Alkermes-sponsored clinical development program evaluating nemvaleukin as a potential immunotherapy for cancer. The ARTISTRY program is comprised of multiple clinical trials evaluating intravenous and subcutaneous dosing of nemvaleukin, both as a monotherapy and in combination with the anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with advanced solid tumors. Ongoing trials in the ARTISTRY program include: ARTISTRY-1, ARTISTRY-2, ARTISTRY-3, ARTISTRY-6 and ARTISTRY-7.

On October 26, 2021 Purple Biotech Ltd. ("Purple Biotech", or the "Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies by overcoming tumor immune evasion and drug resistance, reported the expansion of an existing research agreement, led by Menashe Bar-Eli, Ph.D., Professor, Department of Cancer Biology, at The University of Texas MD Anderson Cancer Center, and will evaluate the potential efficacy of the combination of NT219, a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3, and immuno-oncology drugs, such as anti-CTLA4 or anti-PD1/PDL1 antibodies (Press release, Purple Biotech, OCT 26, 2021, View Source [SID1234591959]).

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"Previously completed preclinical studies have shown that NT219 is able to overcome resistance to certain treatment approaches, with results demonstrating sensitization of various tumor types to the approved therapies," said Hadas Reuveni, Ph.D., VP Research and Development of Purple Biotech. "This new research leverages preclinical data depicting the interface of the lymphoid and myeloid systems within the biology, as well as a target in human cancer. It provides an opportunity to address the alterations of metabolism of both the tumor and the responsive human immune system, altering a "cold" tumor unresponsive to immune oncology approaches into a responsive "hot" one. This collaboration will also provide an opportunity to assess potential synergies mitigating anti-apoptotic mechanisms associated with TGFbeta and the canonical WNT pathway."

"Our prior preclinical studies with NT219 demonstrated its effect on the STAT3 and IRS pathways and the encouraging clinical data presented at ASCO (Free ASCO Whitepaper) 2021 supports the further evaluation of potentially combining NT219 with immunotherapy agents," said Dr. Reuveni. "We look forward to understanding the potential impact of such combinations through this expanded research collaboration. Based on the profile of NT219 and the data generated to date, we believe there are multiple potential benefits that can be derived by combining NT219 with certain immuno-oncology drugs."

"We are thrilled to expand this collaboration, and we believe that combining NT219 with immune-oncology backbone therapies is an important path forward for our NT219 clinical program," said Isaac Israel, Chief Executive Officer of Purple Biotech. "The collaboration is an important step in the translational work that could support the advancement of this potential treatment into the clinic. We recently presented promising initial clinical data for NT219 as a monotherapy treatment for advanced solid tumors and look forward to the availability of additional top-line data from the first part of this ongoing Phase 1/2 clinical trial."

Previous research conducted by Dr. Bar-Eli demonstrated that treatment of mice-bearing melanoma with early generation compounds of NT219 inhibited tumor growth and metastasis by blocking STAT3 and IGF1R/IRS signaling. The inhibition of downstream pro-angiogenic and pro-invasion factors in-vivo, such as VEGF, MMP-2 and IL-8, was shown, as well as the suppression of macrophage recruitment to the tumor microenvironment.

On October 26, 2021 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for cancer and other serious diseases, reported that it will be hosting a virtual R&D Day event detailing the company’s proprietary NAM-enabled natural killer (NK) cell therapy pipeline today, Tuesday, October 26, at 8:00 a.m. ET (Press release, Gamida Cell, OCT 26, 2021, View Source [SID1234591977]). During the event, the company will highlight Gamida Cell’s new programs leveraging next-generation, NAM-enabled, genetically modified NK cells in development for solid tumors and hematological cancers, as well as provide an update on the clinical development of GDA-201, its lead cryopreserved, off-the-shelf cell therapy candidate for the treatment of patients with follicular and diffuse large B cell lymphomas, including an update on the status of its Phase 1/2 Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA).

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Update Regarding IND Application for GDA-201:

The company recently submitted an IND application to FDA for a Phase 1/2 trial with a cryopreserved formulation of GDA-201 in patients with diffuse large B cell lymphoma and follicular lymphoma and was notified that the IND application has been placed on Clinical Hold prior to the initiation of patient dosing. The FDA has requested modifications in donor eligibility procedures and sterility assay qualification. Gamida Cell is in active communication with the FDA with the objective to promptly address these requests to potentially enable the requirements for IND acceptance and study initiation. The initiation of the planned Phase 1/2 trial of GDA-201 may be delayed beyond the end of 2021, pending the outcome of FDA interactions.

"While we work to resolve outstanding issues with our IND, we are pleased to be able to share updates regarding our NAM-enabled NK cell programs," said Julian Adams, Ph.D., Chief Executive Officer of Gamida Cell. "We believe that the issues raised by FDA are addressable and can hopefully be resolved in an expeditious manner. In the meantime, we are pleased to elaborate on the power of NAM combined with the genomic tools that we have harnessed to enable us to create potentially transformative immuno-oncological therapies that may move beyond what is currently possible with existing approaches. These advances in our NK cell pipeline will help to further our mission to bring cancer patients potentially curative cell therapies."

Update Regarding NK Cell Therapy Programs:

During today’s virtual event, Gamida Cell management and partners will provide an overview of the company’s NK cell programs, including:

Objective to improve treatment of both hematological cancers and solid tumors in which genetic modifications to allogeneic NK cells may overcome immunosuppressive microenvironments.
Review of Gamida Cell’s proprietary NAM expansion process, which enhances the potency, function and persistence of NK cells while improving homing to and retention in lymphoid tissues.
Descriptions of Gamida Cell’s genetically modified NK cell immunotherapy programs (GDA-301, GDA-401, GDA-501 and GDA-601), which utilize CAR- and CRISPR-mediated strategies to increase targeting, potency and persistence against hematologic malignancies and solid-tumors.
Discuss a research collaboration with the Dana-Farber Cancer Institute studying the in vitro natural killer (NK) cell killing activity of GDA-601, Gamida Cell’s nicotinamide (NAM)-enabled genetically modified NK cell therapy in multiple myeloma. GDA-601 is a CD38 CRISPR knockout combined with a CD38 CAR NK cell construct that has demonstrated promising preclinical results, including reduced fratricide and increased cytotoxicity against a multiple myeloma cell line.
Phase 1 data on the safety and efficacy of GDA-201, a NAM-enabled, unmodified allogeneic NK cell therapy that has produced positive clinical results in the treatment of diffuse large B cell lymphoma and follicular lymphoma, both of which have significant unmet need.
"This is an exciting time for Gamida Cell as we have expanded R&D activities to augment our NK cell pipeline," said Ronit Simantov, M.D., Chief Medical Officer of Gamida Cell. "During today’s event, we will share our plans to advance the clinical development of GDA-201 based on highly encouraging clinical data in patients with lymphoma that have arisen from a physician sponsored study. We also plan to illustrate how our proprietary NAM expansion process, combined with our advanced genetic modifications, differentiate our NK cell programs as may meaningfully help patients with solid tumors and hematologic malignancies."

A replay of the webcast will be available on the "Investors & Media" section of Gamida Cell’s website at www.gamida-cell.com, and will be available for at least 14 days following the event.

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, as reported at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition1. 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.