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.

On January 24, 2022 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported the presentation of results of two trials evaluating eryaspase in advanced pancreatic cancer at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) on January 21, 2022 (Press release, ERYtech Pharma, JAN 24, 2022, View Source [SID1234606729]).

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Abstract # 581 – rESPECT: A Phase I dose-escalation study of eryaspase in combination with modified FOLFIRINOX in locally advanced and metastatic pancreatic ductal adenocarcinoma: Interim update (NCT04292743).

Dr Marcus Noel, MD, medical oncologist at Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, USA, and principal investigator of the rESPECT trial, presented an interim update of this Phase 1 trial evaluating eryaspase in combination with mFOLFIRINOX, a fluoropyrimidine- and irinotecan-based chemotherapy regimen, as first-line treatment for advanced pancreatic cancer.

To date, eleven patients have been enrolled with a mean age of 68. Three patients were enrolled at a dose level of 75 U/kg and eight at a dose level of 100 U/kg. The novel combination of mFOLFIRINOX plus eryaspase was well tolerated and no dose limiting toxicity (DLT) was observed. The maximum tolerated dose (MTD) has been declared with 5-FU 2400 mg/m2, Oxaliplatin 85 mg/m2, Irinotecan 150 mg/m2 and eryaspase 100 units/kg.

Among ten patients with imaging available to evaluate response, 5 (50%) had partial response (PR) and 5 (50%) had stable disease (SD), corresponding to a disease control rate (PR + SD) of 100%. One patient with locally advanced disease became eligible for resection after receiving therapy.

Dr Marcus Noel, MD, Principal Investigator of the rESPECT IST, commented: "The early results from the rESPECT study are highly encouraging for the combination of eryaspase and modified FOLFIRINOX in first-line pancreatic cancer, with the MTD now established and initial signs of clinical activity demonstrated. We plan to expand enrolment on rESPECT to further evaluate efficacy. Alongside a group of international experts, we are now in the process of potentially considering a larger study in light of both our experience with rESPECT to date and the results observed in patients treated with the combination of eryaspase and FOLFIRI in TRYbeCA-1."

Abstract # 518 – TRYbeCA-1: A randomized, Phase 3 study of eryaspase in combination with chemotherapy versus chemotherapy alone as second-line treatment in patients with advanced pancreatic adenocarcinoma (NCT03665441).

Prof. Pascal Hammel, MD, PhD, medical oncologist at University Paris-Saclay, Hôpital Paul Brousse (APHP), France, and co-principal investigator of the TRYbeCA-1 trial, presented the final results of this Phase 3 trial. The top-line results had been reported in October 2021.

As reported before, the trial did not meet primary efficacy endpoint of overall survival (OS). The median OS for patients treated with eryaspase plus chemotherapy was 7.5 months (95% CI, 6.5-8.3), compared to 6.7 months (95% CI, 5.4-7.5) for chemotherapy alone.

The prespecified subgroup of patients treated with eryaspase and FOLFIRI, a fluoropyrimidine- and irinotecan-based chemotherapy regimen, demonstrated a nominal increase in median OS of 2.3 months versus FOLFIRI alone, from 5.7 to 8 months (HR = 0.81; 95% CI, 0.6-1.1). The FOLFIRI treated patients represented approximately 42% of the patients in this trial.

The treatment was well tolerated, and the addition of eryaspase did not enhance the cytotoxicity of chemotherapy.

Following Prof. Hammel’s presentation, the discussant, Dr Nilofer Saba Azad, MD, Department of Oncology, Johns Hopkins Sidney Kimmel Cancer Center, concluded that TRYbeCA-1 was well designed with appropriate power and stratification factors. Furthermore, the study findings open the possibility for additional study of eryaspase in combination with FOLFIRI in neo-adjuvant, adjuvant and first-line settings.

"While it was initially disappointing to be unable to demonstrate an improvement in survival across the entire population in one of the largest prospective second-line pancreatic cancer studies conducted to date, TRYbeCA-1 has improved our understanding of pancreatic cancer in this setting, and importantly, has also identified a potential utility of the combination of eryaspase with fluoropyrimide- and irinotecan-containing regimens in this difficult to treat cancer. I look forward to furthering discussions with the pancreatic cancer community on future potential clinical trials with eryaspase," said Prof. Pascal Hammel, MD, PhD, Co-principal Investigator of the TRYbeCA-1 trial.

Dr Iman El-Hariry, MD, PhD, Chief Medical Officer at ERYTECH, added: "I would like to thank all investigators and patients who are participating and have participated in the rESPECT and the TRYbeCA-1 studies. Pancreatic cancer remains very difficult to treat with few treatment options, but we have been encouraged by the clinical activity observed with eryaspase in both trials. We continue to evaluate the path forward for potential further clinical development focused on evaluating eryaspase in combination with fluoropyrimidine-and irinotecan-based chemotherapy. Meanwhile, the company is currently preparing a BLA to seek approval for eryaspase for the treatment of ALL patients who developed hypersensitivity to E. coli-derived asparaginase, based on the results of a Phase 2 clinical trial sponsored by the NOPHO group1. The Company intends to submit the BLA in the first quarter of 2022, subject to completion of remaining data requested by the FDA."

On January 24, 2022 RhoVac AB ("RhoVac") reported that the Canadian Intellectual Property Office ("CIPO") has issued a "Notice of Allowance", which means that it intends to grant RhoVac’s patent application for RV001 (onilcamotide) cancer vaccine (Press release, RhoVac, JAN 24, 2022, View Source [SID1234606747]). The company has previously been granted patents relating to onilcamotide in USA, Europe and Japan. The Canadian patent will provide RhoVac’s onilcamotide vaccine with broad protection in a key market and significantly strengthens the company’s patent portfolio.

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The Canadian Intellectual Property Office ("CIPO") has communicated its intention to grant RhoVac’s Patent Application No. 2,710,061. The patent covers RhoVac’s onilcamotide cancer vaccine, possible variants of the vaccine and the use of such vaccines in the treatment or prevention of metastatic cancer where RhoC is expressed. Once the issue fee is paid by RhoVac and necessary formalities have been completed by CIPO, the patent will be granted. The patent term will then extend to December 2028, potentially longer if an application for a Certificate of Supplementary Protection is filed and granted in Canada.

Patents from this first patent family have previously been granted in USA, Europe and Japan for treatment with onilcamotide of metastatic cancer expressing the RhoC protein. The Canadian patent, when granted, will complement these granted patents and another pending US application in this family

CEO Anders Månsson comments:"This patent provides very important protection for our cancer vaccine in Canada, which is an important territory for innovative therapies such as onilcamotide. This patent, when granted, will give product protection for our vaccine, along with additional protection for its use in the treatment and prevention of metastatic cancer [where RhoC is expressed], and in combination therapies".

On January 24, 2022 AIM ImmunoTech Inc. (NYSE: American AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders, and viral diseases, including COVID-19, the disease caused by the SARS-CoV-2 virus, reported the publication of positive data from a Phase 1/2 study of intraperitoneal chemo-immunotherapy in advanced recurrent ovarian cancer (Press release, AIM ImmunoTech, JAN 24, 2022, View Source [SID1234606713]). The manuscript titled, "Phase I trial combining chemokine-targeting with loco-regional chemo-immunotherapy for recurrent, platinum-sensitive ovarian cancer shows induction of CXCR3 ligands and markers of type 1 immunity1" was published in the American Association for Cancer Research (AACR) (Free AACR Whitepaper) publication, Clinical Cancer Research.

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The Phase 1/2 study being conducted by the University of Pittsburgh School of Medicine is designed to evaluate the immunologic and potential clinical effectiveness of intensive locoregional sequential intraperitoneal (IP) cisplatin (IPC) with intravenous (iv) paclitaxel followed by peritoneal infusion of a chemokine modulatory (CKM) regimen composed of a cocktail of IP rintatolimod and interferon-alpha (IFNα) for patients with advanced stage ovarian cancer (III-IV) at primary neoadjuvant setting. AIM ImmunoTech provided rintatolimod (Ampligen, a dsRNA acting as TLR3 agonist), for the Phase 1/2 study.

"These results represent an important extension of prior studies using human tumor explants that showed Ampligen’s potentially important role as a TLR3 agonist acting synergistically with high-dose IFNα and celecoxib to selectively enhance Teff cell-attractants while suppressing Treg-attractants in the tumor microenvironment with a concomitant increase in the Teff/Treg ratio. This current study shows that similar findings are seen combining Ampligen with chemokine-targeting and chemo-immunotherapy in patients being treated for recurrent ovarian cancer. The importance of boosting the Teff/Treg ratio in the tumor microenvironment is that it is associated with the conversion of ‘cold’ tumors into ‘hot’ tumors, which have an increased sensitivity to chemo-immunotherapy and an improved chance of showing tumor regression. This, of course, creates the potential for a positive survival advantage," stated David Strayer, MD, Chief Medical Officer, Chief Scientific Officer of the Company and Board Certified in Medical Oncology.

1 Clin Cancer Res January 19 2022 DOI: 10.1158/1078-0432.CCR-21-3659

Thomas Equels, Chief Executive Officer of AIM commented, "We are very pleased with these results. Ampligen has demonstrated broad immunological effects and we believe has the potential to be a key component in the treatment of ovarian cancer. We are grateful to the University of Pittsburg School of Medicine and are excited to provide support for a larger Phase 2 study which we believe has the potential to provide hope for patients and their families, as well as drive significant shareholder value."

Twelve patients were enrolled in Phase 1 portion of the trial and were treated with IP cisplatin, IP Ampligen, and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3 and 4 also received IP IFNα at 2, 6 and 18 million units, respectively. The primary objectives of the study were to evaluate safety, identify Phase 2 recommended dose and characterize changes in the immune TME. Peritoneal resident cells and IP wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, respectively.

Of the 12 patients enrolled in this Phase 1 trial, 9 (75%) were evaluable for safety, toxicity, and other endpoints. The 3 non-evaluable patients did not complete at least 3 cycles, due to platinum hypersensitivity reactions or port complications. Overall, the regimen was well tolerated, apart from the highest dose of IFNα. Most common toxicities for all grades were anemia (58%), hypomagnesemia (50%), hyponatremia (41.7%), arthralgia (41.7%), and fatigue (41.7%). There was one grade 4 hypomagnesemia (8.3%). Dose limiting toxicities of abdominal pain of grade 3 or more were noted in two patients who received 18MU IFNα (cohort 4).

The Phase 2 recommended dose of IFNα was 6 million units every 3 weeks. Median PFS was 8.4 (3-16.4) months. Median overall survival was 30 (8-66) months. The Company believes these survival outcome data provide an encouraging early signal. Overall response rate was 55.6% and the disease control rate (DCR) was 77.8%, consistent with the expected platinum-sensitive response. Among responders, median duration of response was 11.7 (6-16.4) months.

Key Results Highlights

●Determination of the safety profile and identification of Phase 2 recommended dose for the combination of local cisplatin, Ampligen and IFNα, with oral celecoxib;
●Chemo-immunotherapy combination triggers robust transcriptomic changes in peritoneal resident cells obtained in lonitudinal sampling via IP washes;
●Protein content of IP wash fluid captures treatment-induced increases of IFN-induced immune effector molecules; and
●Tumor immune profile at interval debulking shows partial overlap with IP wash, and points to upregulation of genes encoding for perforin and granzyme B.

Longitudinal sampling of the peritoneal cavity via IP washes demonstrated local upregulation of interferon-stimulated genes, including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin and granzymes. These changes were present two days post chemokine modulation and subsided within one week.

"Epithelial ovarian cancer, the most common form of ovarian cancer, is the most aggressive gynecologic cancer and despite aggressive surgery and chemotherapy treatment options, the 5-year survival rate for patients with advanced high grade serous ovarian cancer remains low. I am very encouraged by the results from this study. With our growing body of positive data, I look forward to further advancing development of this important program with the hope of addressing the significant unmet medical need," added Robert P. Edwards MD, Milton McCall Professor and Chairman, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Director of Women’s Health for UPMC.

Based on these encouraging results, the Company plans on supporting a follow-up Phase 2 trial that will specifically define the immunologic and clinical efficacy of tumor loaded αDC1 vaccine in conjunction with the cisplatin/chemokine modulatory combination regimen will be conducted.