On January 24, 2022 SQZ Biotechnologies Company (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, reported that the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for SQZ-eAPC-HPV, authorizing the company to proceed with initiating a Phase 1/2 clinical trial of the novel cell therapy candidate (Press release, SQZ Biotech, JAN 24, 2022, View Source [SID1234606709]). The company plans to initiate its COMMANDER-001 Phase 1/2 clinical trial of SQZ-eAPC-HPV in patients who have HPV16+ solid tumors, including head and neck, cervical, and anal cancers, and have progressed following standard therapies.

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SQZ-eAPC-HPV is created by delivering five different mRNAs into a patient’s monocytes, B cells, T cells, and NK cells – engineering four cell types with five functions in a single step. In preclinical models, SQZ eAPCs have been shown to generate robust CD8 T cell responses against multiple antigens, including HPV16 proteins, through simultaneous expression of antigens, CD86, membrane bound IL-2, and membrane bound IL-12.

"We believe SQZ eAPCs represent a major advance in cell therapy with the largest number of multiplexed components ever advanced into clinical testing. We are incredibly excited to explore its potential for patient impact," said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. "SQZ eAPCs build upon the promising preliminary monotherapy clinical activity shown by our first SQZ APC platform. Through multiplexed engineering of a patient’s monocytes, B cells, T cells, and NK cells, we are able to integrate antigen presentation and enhanced immunological functions into a single clinical candidate that could become a powerful weapon against solid tumors."

By focusing on engineering physiological mechanisms, SQZ cell therapies do not require patient pre-conditioning and have thus far been well tolerated in clinical study. Similar to our other clinical programs, SQZ eAPCs can be manufactured in under 24 hours and have the potential for future implementation on our point-of-care platform.

The SQZ eAPC trial is the third FDA IND clearance for a clinical candidate based on the company’s Cell Squeeze technology.

About SQZ-eAPC-HPV

SQZ Enhanced Antigen Presenting Cells (eAPC) are derived from peripheral blood mononuclear cells (PBMCs), which are primarily composed of monocytes, T cells, B cells, and

img61662729_0.jpgEmpowering Cells to Change Lives

NK cells, and engineered with various mRNA encoding for multiple target antigens and immuno-stimulatory signals, including CD86 and membrane bound IL-2 and IL-12. The company presented preclinical findings in November 2021 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) showing that SQZ eAPCs generated robust T cell responses in human in-vitro models. Additionally, it was demonstrated that HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting eAPC clinical development in broad HPV16+ patient populations.

COMMANDER-001 Trial Design

SQZ-eAPC-HPV is being evaluated in a Phase 1/2 clinical trial (COMMANDER-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with pembrolizumab, an immune checkpoint inhibitor. The study consists of two parts. The first part is designed to assess safety and tolerability of multiple doses of SQZ-eAPC-HPV in treatment-experienced patients, following a dose escalation scheme for monotherapy, and a dose de-escalation for the combination with pembrolizumab. The second part of the study will assess clinical response in less treatment-experienced patient populations.

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 January 24, 2022 TScan Therapeutics, Inc. (Nasdaq: TCRX), a biopharmaceutical company focused on the development of T-cell receptor (TCR) engineered T cell therapies (TCR-T) for the treatment of patients with cancer, reported that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application to evaluate TSC-100 for the treatment of patients with hematologic malignancies who are undergoing allogeneic hematopoietic cell transplantation (HCT) (Press release, TScan Therapeutics, JAN 24, 2022, View Source [SID1234606728]). The target of TSC-100 is the minor histocompatibility antigen HA-1, which is a lineage-specific antigen found on blood cells. The Company will now submit the clinical protocol to Institutional Review Boards (IRB) for the initial study sites and expects to begin dosing patients in the first half of 2022.

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TSC-101 is targeted to the lineage-specific blood cell antigen HA-2, which is a novel target for cell therapy. The Company received a brief communication from the FDA indicating that the TSC-101 IND has been placed on hold pending additional assessment of the risk of off-tumor reactivity for TSC-101. The Company expects to receive further written communication from the FDA in the near future and plans to work with the agency to resolve its questions as quickly as possible.

"FDA clearance of our IND application for TSC-100 is an important milestone for our lead liquid tumor program as it marks the first clinical-stage product candidate to advance from our pipeline of therapies geared to treat unmet needs in major cancer indications," said David Southwell, President and Chief Executive Officer. "We are excited about the potential of both TSC-100 and TSC-101 to prevent relapse in leukemia patients following HCT. We are looking forward to initiating our Phase 1 multi-arm clinical trial in the first half of this year, with preliminary data expected in the second half of 2022. We will be opening the TSC-101 arm upon FDA clearance of the TSC-101 IND."

"FDA clearance of our TSC-100 IND is significant as it allows us to move forward with the umbrella clinical protocol for our hematologic cancer study," said Gavin MacBeath, Chief Scientific Officer. "This is a great accomplishment for our organization and validation of our TCR discovery platform. Importantly, the INDs for TSC-100 and TSC-101 were based on our proprietary T-Integrate cell engineering platform, which includes our advanced non-viral vector and our in-house GMP manufacturing capabilities. We intend to use this same platform to develop enhanced TCR-T cell therapies for our solid tumor program."

With the acceptance of the IND for TSC-100 in hematologic malignancies, TScan plans to initiate a multi-arm Phase 1 umbrella trial designed to evaluate TSC-100 compared to standard-of-care in patients who are undergoing allogeneic HCT. Pending acceptance from the FDA regarding the IND for TSC-101, the Company will then initiate the TSC-101 arm of this trial in the same patient population. Primary endpoints include safety and dose-finding, and secondary and exploratory endpoints include relapse rate versus standard-of-care as well as qualitative biological readouts including minimal residual disease and kinetics of donor chimerism. Once the recommended Phase 2 dose has been identified, the study will transition to Phase 2 to assess relapse rates of treated patients versus the standard-of-care arm

On January 24, 2022 Illumina, Inc. (NASDAQ: ILMN) and the National Cancer Center Japan reported an international joint research project that will use Illumina’s high-throughput DNA sequencing to analyse the blood-based genomic profile and clinical information of patients living with Nasopharyngeal Carcinoma (Press release, Illumina, JAN 24, 2022, View Source [SID1234606746]). The study will be known as a part of the Asian Multicenter Prospective Study of Circulating Tumor DNA Sequencing (A-TRAIN).

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We are immensely proud to contribute to this international collaboration and prospective study. Through our joint efforts, we will fuel initiatives that improve health outcomes for people living with nasopharynx cancer and progress the development of personalized treatment, especially those in the Asian community where this carcinoma is most prevalent.

We are immensely proud to contribute to this international collaboration and prospective study. Through our joint efforts, we will fuel initiatives that improve health outcomes for people living with nasopharynx cancer and progress the development of personalized treatment, especially those in the Asian community where this carcinoma is most prevalent.
One of the main research areas of the project is nasopharyngeal carcinoma, a rare tumor of the head and neck which originates in the nasopharynx and has a higher incidence rate in Asian countries. More than 80 percent of new cases occur in Asia, with Southeast Asian countries accounting for 67 percent of the global burden of all cancer. Nasopharyngeal cancer ranked ninth among incident cancers and eighth among cancer deaths in Southeast Asia.

"We are immensely proud to contribute to this international collaboration and prospective study," said Gretchen Weightman, Head of Global Commercial Strategy and General Manager of Asia Pacific and Japan at Illumina. "Through our joint efforts, we will fuel initiatives that improve health outcomes for people living with nasopharynx cancer and progress the development of personalized treatment, especially those in the Asian community where this carcinoma is most prevalent."

"As nasopharyngeal carcinoma occurs more frequently in Asia and is more difficult to treat, there is a strong need to develop new treatments," said Dr. Kan Yonemori, Principal Investigator at A-TRAIN. "A comprehensive genome profiling panel is a powerful tool to help solve this problem by using blood for genetic analysis. We are grateful for Illumina’s support in enabling this important research in numerous Asian countries."

The A-TRAIN study led by the National Cancer Center Hospital Japan is an international joint research project in a number of Asian countries to develop novel treatments based on genomic abnormalities for cancers that are common in Asia. The overall project includes research involving patients with cervical cancer, ovarian cancer, ovarian clear cell carcinoma, nasopharyngeal carcinoma, endometrial cancer and breast cancer, the database will be constructed and analysed by examining genomic abnormalities comprehensively by liquid biopsy, together with clinical information such as treatment details and prognosis.

The study will be conducted as part of an international collaborative study under the Asian clinical TriaLs network for cAncerS (ATLAS) project, which aims to accelerate the implementation of clinical research and to develop personalized treatments. In this study, genomic analysis of blood samples of up to 96 patients with nasopharynx cancer will be analyzed using Illumina’s TruSight Oncology 500 ctDNA.

Over the next year, the resulting data will be used by the Japan-led initiative to establish a platform for international collaborative trials with Malaysia, Thailand, the Philippines, Indonesia and Vietnam, which are actively promoting cancer treatment development in the Asian region.

About TruSight Oncology 500
TSO 500 is a Research Use Only comprehensive pan-cancer assay designed to identify 523 known and emerging tumor biomarkers. TSO 500 utilizes both DNA and RNA from tumor samples to identify key variants critical for cancer development and progression, such as small DNA variants, fusions, and splice variants. Based on the content of TSO 500, Illumina will be adding an in vitro diagnostic test to the TruSight Oncology product family. This comprehensive tumor profiling assay will have similar chemistry and analytics to TSO 500. To learn more about TSO 500, click here.

On January 24, 2022 Lyell Immunopharma, Inc., (Nasdaq: LYEL), a T-cell reprogramming company dedicated to the mastery of T cells to cure patients with solid tumors, announced today that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for LYL132, an investigational T-cell receptor (TCR) therapy for patients with solid tumors expressing New York esophageal squamous cell carcinoma 1 (NY-ESO-1) that the company is developing in collaboration with GSK (Press release, GlaxoSmithKline, JAN 24, 2022, View Source [SID1234608902]). LYL132 incorporates Epi-R, Lyell’s epigenetic reprogramming technology and is under investigation as a potential next-generation enhancement to letetresgene autoleucel (lete-cel), a GSK TCR therapy targeting NY-ESO-1 currently in pivotal clinical development . The cell surface antigen NY-ESO-1 is a clinically validated target present on many aggressive solid tumors. Lyell’s Epi-R technology is designed to address a major barrier to successful Adoptive Cell Therapy (ACT) by creating populations of T cells with properties of durable stemness. T cells with properties of durable stemness are able to proliferate, persist, and self-renew with anti-tumor functionality.

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"Clearance of the second IND incorporating Lyell’s novel reprogramming technologies is another important milestone for Lyell, especially coming within a month of FDA clearance of an IND for LYL797, our lead CAR program," said Liz Homans, Chief Executive Officer of Lyell. "We are eager to start multiple clinical trials that utilize our technologies to assess the potential benefits for patients with solid tumor cancers and also remain on track for two additional INDs by the end of this year."

"Clinically assessing, in a validated target, the potential benefit of reprogrammed T cells designed to have properties of durable stemness is a profoundly important and exciting milestone for Lyell and cancer drug development," stated Rick Klausner, MD, Chair of Lyell’s Board of Directors. "We believe lack of durable stemness is a major barrier to successful ACT in solid tumors and expect our Epi-R technology platform will offer a path forward to better outcomes for patients."

The planned Phase 1 trial will assess LYL132 in patients with NY-ESO-1+ advanced synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS). Lyell will manufacture LYL132 in its LyFE Manufacturing Center and GSK will conduct the Phase 1 trial.

About NY-ESO-1, Synovial Sarcoma (SS) and Myxoid/Round Cell Liposarcoma (MRCLS)

NY-ESO-1 is a member of the cancer testis-antigen (CTA) family of tumor-associated antigens and has been previously validated as a therapeutic target in clinical trials. NY-ESO-1 has low or no expression in healthy adult tissues but is detectable in multiple solid tumor cancer types including non-small cell lung cancer, bladder cancer, melanoma, liver cancer, SS and MRCLS. SS is a rare yet highly malignant tumor occurring in soft tissue and accounts for approximately 5-10% of all soft tissue sarcomas, with approximately 650 to 1,300 cases per year. It is more common in adolescents and young adults than in older individuals. Patients often develop metastases, particularly to the lungs, resulting in 10-year survival rates of <50%. MRCLS is a type of liposarcoma, a rare soft connective tissue tumor that grows in cells that store fat in the body, typically in the arms and legs. MRCLS is one of the most common types of liposarcoma and makes up approximately 30% of all cases, with 2,000 diagnosed occurrences in the United States each year. When this type of cancer metastasizes, the 5-year survival rate is approximately 40%.

About LYL132 and the GSK Collaboration

LYL132 is a novel, NY-ESO-1-targeted TCR product that incorporates Epi-R, Lyell’s proprietary epigenetic reprogramming technology designed to create populations of T cells which have the properties of durable stemness – the quality that enables T cells to proliferate, persist, and self-renew with anti-tumor functionality.

Preclinical in vitro and in vivo experiments of LYL132 have demonstrated that LYL132 has T cells with qualities consistent with T cell stemness, including enhanced metabolic fitness and proliferation. We believe these qualities could be associated with improved clinical responses that could further improve first generation approaches.

In 2019 Lyell and GSK entered into a collaboration agreement to research and develop potential T-cell therapies that apply Lyell’s platform technologies and cell therapy innovations to TCRs or chimeric antigen receptor (CAR) therapies under distinct programs for a specified number of targets. Lyell received $250 million in the form of a combined upfront payment and equity investment and is eligible for technology validation payments totaling approximately $200 million and up to approximately $400 million in additional aggregate development and sales milestones for LYL132. In addition to LYL132, a separate GSK-sponsored program evaluating an NY-ESO-1-targeted TCR that incorporates Lyell’s Gen-R genetic reprogramming technology is planned. These programs could represent a single future product opportunity for GSK utilizing one or both of Lyell’s platform technologies.

On January 24, 2022 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported that Brian M. Culley, Lineage’s Chief Executive Officer, will present at the B. Riley Securities 2022 Virtual Oncology Conference, in a fireside chat hosted by Mayank Mamtani, Managing Director, Senior Biotech Research Analyst and Group Head of Healthcare Research at B. Riley Securities (Press release, Lineage Cell Therapeutics, JAN 24, 2022, View Source [SID1234606712]).

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Mr. Culley will provide an update on Lineage’s cell therapy pipeline, including an outline of the clinical development plans for its OPC1 program for the treatment of spinal cord injury and VAC2 for the treatment of solid tumors. Lineage recently received a $50 million upfront payment from Genentech, a member of the Roche Group, under the Company’s exclusive worldwide collaboration for the development and commercialization of OpRegen, an RPE cell therapy for the treatment of ocular disorders. Lineage plans to use a portion of the payment to help support the advancement of its OPC1 and VAC programs noted above, as well as the expansion of its regenerative medicine platform into new disease settings which are yet to be disclosed.

Interested parties can register to view both the live event and replay on the Events and Presentations section of Lineage’s website. Additional videos are available on the Media page of the Lineage website.