On July 10, 2024 Imugene Limited (ASX:IMU), a clinical stage immune-oncology company, reported that the first patient has been dosed in its trial for bile tract cancer (cholangiocarcinoma) patients (Press release, Imugene, JUL 10, 2024, View Source [SID1234644754]).

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!

This is an expansion of the MAST (Metastatic Advanced Solid Tumours) Phase 1 trial after early responses were observed in gastrointestinal cancers, and particularly cholangiocarcinoma, using Imugene’s cancer-killing virus CF33 (VAXINIA).

The first patient in the trial was treated at St. Vincent’s Hospital, with a total of 10 patients to be enrolled.

Imugene Managing Director & CEO Leslie Chong said: "Given the results we’ve seen to date we are eager to see the potential of VAXINIA in bile tract cancer. We look forward to now advancing to the higher doses in the trial to gather further key data and make a genuine difference to patients in need of innovative treatment options."

In November 2023, the FDA granted the VAXINIA MAST clinical program Fast Track Designation for the treatment of bile tract cancer, which allows Imugene closer cooperation with the FDA to expedite the program and potential approval process.

Bile tract cancer is a rare disease in which malignant cancer cells form in the bile ducts. It is difficult to treat and generally responds poorly to immunotherapy drugs.

One patient with bile tract cancer who had failed three prior lines of therapy received a mid-dose of IT-administered monotherapy VAXINIA achieved a complete response, meaning the disappearance of all signs of cancer in response to treatment, and the patient has been on the study for over 620 days. A second patient with cholangiocarcinoma, who has also progressed on prior drug therapies, achieved stable disease for more than four months upon receiving IV-administered VAXINIA.

The Cohort Review Committee has now cleared the fifth cohort for both arms, intratumoral (IT) and intravenous (IV), of the monotherapy dose escalation portion of the MAST trial, with no safety signals observed thus far. Consequently, the sixth cohort of each arm of the dose escalation trial are now open and enrolling.

*Further dose escalation to continue as long as no safety issues are observed

The multicenter, Phase 1, MAST trial commenced by delivering a low dose of VAXINIA to patients with metastatic or advanced solid tumours who have had at least two prior lines of standard of care treatment. With no safety signals identified to date, the trial has since progressed through the monotherapy dose escalation cohorts as well as the combination study, whereby VAXINIA is administered with well-known checkpoint inhibitor pembrolizumab. CF33 oncolytic virus, developed by City of Hope, has been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumours in preclinical laboratory and animal models¹.

On July 9, 2024, bluebird bio, Inc. (the "Company") reported to have entered into an amendment (the "Second Amendment") to its Loan and Security Agreement (the "LSA"), dated as of March 15, 2024, as amended on April 30, 2024, by and among the Company, the several banks and other financial institutions or entities party thereto, as lenders (collectively, the "Lenders"), and Hercules Capital, Inc., as administrative agent and collateral agent (the "Agent") (Filing, 8-K, bluebird bio, JUL 9, 2024, View Source [SID1234644788]).

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!

Pursuant to the Second Amendment, the Company, the Agent and the Lenders agreed to, among other things: (i) extension of the period during which the Company will provide revised monthly financial reporting metrics to the Lenders; and (ii) extension of the deadlines by which the Company must provide to the Lenders financial statements for the year ended December 31, 2023 and for each of the quarters ended March 31, 2024 and June 30, 2024. Further, the Second Amendment provides that the Company’s late delivery and filing of its Form 10-K for the year ended December 31, 2023 and Forms 10-Q for the quarters ended March 31, 2024 and June 30, 2024 shall not be deemed a violation of the Company’s covenant to maintain compliance with applicable law, so long as such documents are filed by the extended deadlines.

The foregoing description of the Second Amendment does not purport to be complete and is qualified in its entirety by the full text of the Second Amendment, a copy of which is filed as Exhibit 10.1 to this Current Report on Form 8-K and incorporated herein by reference.

On July 9, 2024, Bicycle Therapeutics plc (the "Company") reported that it has repaid in its entirety and voluntarily terminated its loan and security agreement, dated September 30, 2020 (as amended from time to time, the "Loan Agreement"), by and among the Company, certain of its subsidiaries and Hercules Capital, Inc. ("Hercules") (Filing, 8-K, Bicycle Therapeutics, JUL 9, 2024, View Source [SID1234644767]). The Loan Agreement provided for term loans in an aggregate principal amount of up to $75.0 million (the "Term Loans"), of which $30.0 million was outstanding and which bore interest at an annual rate equal to the prime rate as reported in the Wall Street Journal plus 4.55%, with a minimum annual rate of at least 8.05%, capped at a rate no greater than 9.05%.

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 Term Loans were scheduled to mature on July 1, 2025. The Company elected to repay all amounts outstanding, including accrued and unpaid interest, an end-of-term charge of $1.5 million and a prepayment charge of $0.3 million, for a total aggregate payment of $31.9 million, using cash on hand. As collateral for the obligations under the Loan Agreement, the Company granted to Hercules a senior security interest in all of Company’s right, title and interest in, to and under substantially all of Company’s personal property and other assets, other than its intellectual property, and, upon the termination of the Loan Agreement, all security interests granted to the secured parties thereunder were terminated and released.

The Loan Agreement also included customary affirmative and restrictive covenants, representations and warranties and events of default, as more fully set forth in the Loan Agreement.

On July 9, 2024 Factor Bioscience Inc., a Cambridge-based biotechnology company focused on developing mRNA and cell-engineering technologies, reported its participation in the International Society for Stem Cell Research (ISSCR) 2024 Annual Meeting to be held in Hamburg, Germany from July 10-13, 2024 (Press release, Factor Bioscience, JUL 9, 2024, View Source [SID1234644763]). Factor will deliver six presentations covering the latest preclinical data from Factor’s cell engineering platforms.

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!

"We are excited to showcase our recent progress on developing next-generation therapies based on cutting-edge stem cell science at ISSCR 2024," said Dr. Matt Angel, Co-Founder, Chairman and CEO of Factor. "The work that we will be presenting this week represents more than a decade of focused effort. We are committed to developing these new medicines to enable a brighter future for patients and their families."

Dr. Kyle Garland, Factor’s Director of Translational Science, added, "Our six presentations at ISSCR 2024 will cover several novel and unique stem cell technologies, including iPSC-derived macrophages engineered with mRNA to enhance T cell cytotoxicity to solid tumor cells. We are excited to share these and other advances in Hamburg over the next few days."

Details of the presentations are below:

"Engineered iPSC-Derived Macrophages Evade Host-Versus-Graft Alloreactivity and Enhance T Cell Cytotoxicity to Triple Negative Breast and Ovarian Cancer Cells In Vitro." -to be presented by Ian Hay on July 12 from 1:30-3:00 pm CEST, PSC-Based Cell Therapies Session (Oral Presentation), Hall 3 – Entrance Level.

"B2M-KO iMSCs Better Suppress T Cell Proliferation by Upregulating IDO1 in Response to Proinflammatory Signals." -to be presented by Raven Dance Hinkel on July 10 from 5:45-6:45 pm CEST, Clinical Applications (CA) Session I: (Poster Presentation #165), Hall H – Entrance Level.

"Donor-Sequence Optimization Enables Targeted Insertion of Complex Stealthing Constructs in mRNA-Reprogrammed Induced Pluripotent Stem Cells." -to be presented by Elizabeth Belcher on July 10 from 6:45-7:45 pm CEST, Clinical Applications (CA) Session I: (Poster Presentation #228), Hall H – Entrance Level.

"Novel Polyvalent Ionizable Lipids Enable Targeted Delivery of mRNA to Immune Cells and iPSC-derived MSCs." -to be presented by Ariadna Lubinus on July 11 from 3:45-4:45 pm CEST, New Technologies (NT) Session II: (Poster Presentation #509), Hall H – Entrance Level.

"Novel Regulatory Sequences Drive Persistent Transgene Expression During Directed Differentiation of iPSCs to Lymphocytes and Macrophages." -to be presented by Claire Aibel on July 11 from 4:45-5:45 pm CEST, New Technologies (NT) Session II: (Poster Presentation #368), Hall H – Entrance Level.

"Reporter-Free Generation of iPSC-derived Tissue-Specific Cells Engineered for the Stable Expression of Immunomodulatory Proteins." -to be presented by Taeyun Kim on July 11 from 4:45-5:45 pm CEST, New Technologies (NT) Session II: (Poster Presentation #394), Hall H – Entrance Level.
For more information about the International Society for Stem Cell Research (ISSCR) 2024 Annual Meeting, visit www.isscr2024.org.

On July 9, 2024 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to OBX-115, a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15), for the treatment of patients with metastatic or locally advanced melanoma that is refractory to or has relapsed after PD-1/PD-L1–based immune checkpoint inhibitors (ICI) (Press release, Obsidian Therapeutics, JUL 9, 2024, View Source [SID1234644762]).

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!

"FDA Fast Track Designation underscores the ongoing unmet need for patients with melanoma that has progressed on or after ICI therapy, agnostic of mutational status, and that OBX-115 may have the potential to address that unmet need," said Madan Jagasia, M.D., Chief Executive Officer of Obsidian. "OBX-115 is poised to be a transformative treatment option due to its patient-centric focus, including compatibility with core needle biopsy tumor tissue procurement and positively differentiated safety and tolerability profile relative to non-engineered TIL cell therapy. We are highly encouraged by the most recent safety and efficacy data presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Meeting. With this designation, we look forward to continued collaborative interaction with the FDA as we advance OBX-115 clinical development in the broad post-ICI setting."

Fast Track Designation is intended to facilitate development and expedite the review of new drug candidates that address serious and life-threatening conditions so that an approved product can reach the market expeditiously. Features of Fast Track Designation include frequent interactions with the FDA review team, and if relevant criteria are met, eligibility for Priority Review and Rolling Review.

OBX-115 is being investigated in a multicenter trial in advanced or metastatic melanoma and non-small cell lung cancer (NSCLC) (NCT06060613). Enrollment has been completed for the first-in-human, single-center study of OBX-115 (NCT05470283).

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. OBX-115 is being investigated in two ongoing clinical trials in advanced or metastatic melanoma and non-small cell lung cancer (NSCLC) (NCT05470283 and NCT06060613).