On July 10, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported an update on the on-going OPTIMIZE-1 clinical Phase 2 trial with the company’s lead asset, mitazalimab (Press release, Alligator Bioscience, JUL 10, 2024, View Source [SID1234644766]). All patients in the 450 µg/kg back-fill cohort have been enrolled.

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The additional cohort was enrolled in order to provide further dose characterization following advice from the FDA, to ensure mitazalimab Phase 3 readiness.

"We are pleased to see the recruitment completed in a very swift manner, a testament to the committed work by the Alligator team and the great engagement of the study investigators and their research staff involved in the OPTIMIZE-1 trial", said Søren Bregenholt, CEO of Alligator Bioscience. "We are committed to bringing mitazalimab to patients as soon as possible, and this back-fill cohort is an important step to complete the dose-characterization and ensure mitazalimab’s Phase 3-readiness in accordance with the guidance from FDA."
OPTIMIZE-1, an open-label, single-arm, multicenter, Phase 1b/2 study, assessed the safety and efficacy of mitazalimab (CD40 mAb agonist) in combination with standard of care chemotherapy mFOLFIRINOX in 1st line pancreatic cancer. On June 26, the 18-month follow-up analysis was reported, demonstrating robust data with substantial survival benefits compared to standard of care chemotherapy.

About pancreatic cancer

Pancreatic cancer is the 12th largest cancer by number of patients. It is expected to become the second leading cause of cancer death in the western world by 2030. There are about 200,000 annual cases in the U.S. and the EU, with very poor prognosis: five-year survival is about 10% and median survival about 6 months. For 80% of patients, the only option is chemotherapy that offers only marginal benefit. FOLFIRINOX is expected to be the preferred first line regimen in the U.S. and the EU for patients with good performance status.

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]).

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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]).

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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%.

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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.

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"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.