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.

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]).

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"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).

On July 9, 2024 Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumorally injected cancer therapies intended to kill tumors directly and increase immune system recognition of cancers, reported that the first U.S. patient has been dosed in the Company’s Phase 3 study to treat metastatic sarcoma (NCT06263231) (Press release, Intensity Therapeutics, JUL 9, 2024, View Source [SID1234644761]). The trial is a superiority study testing INT230-6 as monotherapy compared to the investigator’s choice of three current standard-of-care systemic chemotherapy drugs in second or third-line metastatic, recurrent, or inoperable soft tissue sarcomas ("STS").

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The global Phase 3 study is expected to enroll approximately 333 patients. The primary endpoint is overall survival. For every three patients treated, two will receive INT230-6, and one will receive the standard of care. STS subtypes being enrolled are leiomyosarcoma, liposarcoma, and undifferentiated pleomorphic sarcoma. The Phase 3 initiation follows reported data from the Company’s Phase 1/2 trial, where INT230-6 showed tumor-killing and immune-activating properties with increased survival in metastatic disease.

"We have now dosed our first patient in the U.S. and have filed regulatory documents to initiate this trial in Canada and Europe. Over the next several months, we anticipate initiating sites in eight countries. Sarcoma is a deadly cancer with a median overall survival following second and third-line drug treatments of between 10 and 15 months," said Intensity Therapeutics’ Founder, Chairman, and CEO, Lewis H. Bender. "During our phase 1/2 metastatic dose escalation study, in a sarcoma population that had progressed following a median of 3 lines of therapy, we reported a median overall survival of 21.3 months with our drug alone. Patients, their caregivers, and physicians worldwide desperately need improved treatment options and we are excited to have finally begun testing our new approach in Phase 3. I want to take this opportunity to thank our dedicated team for getting us to this tremendous milestone."

About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug comprises two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct killing of the tumor, INT230-6 releases a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy.

About Sarcoma

Soft tissue sarcoma is a rare type of cancer that starts with the growth of cells in the body’s soft tissue, such as muscle, fat, blood vessels, nerves, tendons, and linings of the joints. The disease mostly occurs in the arms, legs and belly. There are 197,000 patients in the US living with sarcoma and more than 50 types of soft tissue sarcoma, the treatment of which first involves surgery. Other treatments might include radiation therapy and then chemotherapy. Using the U.S. SEER database, the Company estimated that 14,337 patients have regional or distal (metastatic) leiomyosarcoma, liposarcoma, and undifferentiated pleomorphic sarcoma.