On November 13, 2024 ImmuneOnco Biopharma reported that Company has initiated the Phase II clinical trial of IMM27M for estrogen receptor positive (ER+) advanced breast cancer that failed after endocrine therapy or recurred and has enrolled the first patient (Press release, ImmuneOnco Biopharma, NOV 13, 2024, View Source [SID1234655705]). In addition, the Phase I dose-escalation study of IMM27M was completed in late 2023, demonstrating the following results (as of August 6, 2024): • In the Phase I trial, a total of eight evaluable ER+ advanced or metastatic breast cancer patients were enrolled. Among them, two achieved partial response (PR) and four patients had stable disease (SD), resulting in an overall response rate (ORR) of 25.0% and a disease control rate (DCR) of 75.0%; • Positive preliminary efficacy signals were demonstrated; and • IMM27M was found to be safe and well-tolerated, with no dose-limiting toxicity observed at the highest explored dose level of 7.5 mg/kg in Phase I.

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The recommended Phase II dose (RP2D) for monotherapy has been determined to be 5.0 mg/kg administered once every three weeks (Q3W).

ABOUT IMM27M
IMM27M is a new generation cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity. It caninduce potent immune responses targeting CTLA-4 overexpressed immune-suppressive Tregulatory (Treg) cells and promote Treg depletion from the tumor microenvironment (TME),thus enhancing T-cell antitumor response.

On November 13, 2024 TAE Life Sciences (TLS), TAE Life Sciences, in collaboration with Kyoto University and Principal Investigator Dr. Fuyuhiko Tamanoi, reported groundbreaking preclinical results in Boron Neutron Capture Therapy (BNCT). Utilizing TAE Life Science’s novel boron-10 drugs and Kyoto University Research Reactor (KURR) neutron source has generated significant pre-clinical data that may redefine the potential of BNCT in cancer treatment (Press release, TAE Life Sciences, NOV 13, 2024, View Source [SID1234649553]).

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Recently published in the Journal of Medicinal Chemistry (J. Med. Chem. 2023, 66, 13809−13820) and complemented by a newly submitted manuscript to ACS Central Science, our
research highlights a remarkable phenomenon known as the abscopal effect. This effect, where localized radiation treatment results in the shrinkage of tumors at untreated sites, holds profound implications for treating metastatic and micro-metastatic cancer.

In a key study using immune-competent balb/c mice, BNCT treatment of subcutaneous tumors on one leg completely inhibited tumor growth when the same tumor cells were reintroduced to the opposite leg two weeks post-treatment. These results, some of the most impressive preclinical data seen to date, suggest that BNCT can stimulate an immune response capable of generating memory cells to prevent tumor recurrence at distant sites.

"In one experiment, a mouse colon tumor was grown in the leg of a mouse and a second tumor was grown in its shoulder. BNCT was applied to the tumor in the leg, while the shoulder tumor was shielded from treatment. Remarkably, the untreated shoulder tumor exhibited a 34% reduction and slower growth rate compared to the control group, highlighting a potential systemic effect of BNCT."

"While the abscopal effect is not new in radiation oncology, these results with BNCT represent a significant step forward", said Dr. Sunil Krishnan, Radiation Oncologist and Professor at the Center for Translational Cancer Research at UT Health Houston. "What’s particularly exciting is that this level of immune response and tumor control has not traditionally been observed with standard x-ray-based radiation therapy. It underscores the potential for BNCT to not only address
primary tumors but also impact metastatic disease in a way we haven’t seen before."

Further investigations are underway to explore the mechanisms behind these results, focusing on the role of dendritic cells, T-cells, and macrophages in immune memory. Additionally, TAE Life Sciences is evaluating the combination of BNCT with immune checkpoint inhibitors, such as anti-CTLA4, anti-PD1, and anti-PDL1, to enhance outcomes in tumors with both "hot" (active immune profile) and "cold" (inactive immune profile) immune phenotypes.

"We are excited to demonstrate both the vaccine effect and the abscopal effect in preclinical BNCT experiments," said Kendall Morrison, Chief Scientific Officer at TAE Life Sciences.
"This research reinforces BNCT’s potential not only as a localized therapy but also as a treatment capable of addressing metastatic cancer. Combining BNCT with immunotherapy agents could significantly transform cancer treatment outcomes."

If these preclinical results can be translated to clinical applications, it could pave the way for improved responses to immune checkpoint blockade therapies, particularly for challenging "cold" tumors.

On November 13, 2024 PhotoCure reported its quarterly results (Presentation, PhotoCure, NOV 13, 2024, View Source [SID1234649494]).

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On 13 November 2024 Photocure ASA (OSE:PHO) reported Hexvix/Cysview revenues of NOK 120.1 million in the third quarter of 2024 (Q3 2023: NOK 107.3 million), and EBITDA of NOK 5.0 million (NOK 3.3 million) for the Company (Press release, PhotoCure, NOV 13, 2024, View Source [SID1234649493]). Photocure reiterates its 2024 financial guidance and continues to expect consolidated product revenue growth of 6% to 9% in constant currency and positive EBITDA excluding business development expenses.

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"We delivered solid performance in the third quarter, generating 12% Hexvix/Cysview revenue growth and NOK 5.0 million in EBITDA. Year-to-date, we have reported 9% growth in product revenues. Our business segments in North American and Europe both generated positive contributions during the quarter, and we made progress on key initiatives that we are pursuing to accelerate our growth going forward," says Dan Schneider, President & Chief Executive Officer of Photocure.

Photocure reported total group revenues of NOK 120.2 million in the third quarter of 2024 (NOK 107.5 million), and EBITDA* of NOK 5.0 million (NOK 3.3 million), driven by revenue growth in North America and Europe. Hexvix/Cysview revenues ended at NOK 120.1 million in the quarter (Q3 2023: NOK 107.3 million). The EBIT was NOK -2.2 million (NOK -3.9 million) and the cash balance at the end of the period was NOK 291.1 million.

At the end of the third quarter of 2024, the installed base of rigid BLC systems in the U.S. was 387, up 13% since Q3 2023. This includes 18 mobile towers owned by ForTec Medical. Photocure estimates that 25 flexible BLC towers remain in the U.S. market. Photocure also entered into a strategic agreement with Richard Wolf GmbH to develop and commercialize a next-generation flexible blue light cystoscope based on Richard Wolf’s system blue technology with the goal to reintroduce and grow the use of BLC with Cysview/Hexvix in the surveillance setting.

"We are also positioning for the future with our Richard Wolf partnership to develop and commercialize a state-of-the-art flexible high-definition blue light system. This partnership is focused on ensuring that physicians and patients have reliable access to high quality BLC equipment in the surveillance setting. The development project is well underway, with the goal to bring a new flexible BLC system to patients globally as soon as possible. Additionally, the Karl Storz’ Citizen’s Petition to have BLC equipment reclassified in the U.S. from Class 3 to Class 2 is another significant opportunity that we continue to monitor and pro-actively support," Schneider adds.

Photocure believes that the benefits of Blue Light Cystoscopy with Hexvix/Cysview offering superior detection and management of bladder cancer will continue to be adopted and become the standard of care. Photocure reiterates its 2024 guidance and continues to expect consolidated product revenue growth of 6% to 9% in constant currency, positive EBITDA excluding business development expenses, and new and upgraded Saphira installations in the U.S. in the range of 55 to 70 towers.

"With our business continuing to show steady growth, industry trends in our favor, and a number of initiatives underway that can enable Hexvix/Cysview to grow faster, I believe that Photocure is well-positioned to deliver value to patients and our shareholders in the coming quarters," Schneider concludes.

On November 13, 2024, Syros Pharmaceuticals, Inc. (the "Company") reported to have gave notice to QIAGEN Manchester Limited ("QIAGEN") of its election to terminate the Master Collaboration Agreement dated March 7, 2022 (the "Agreement") relating to the development and commercialization of an assay as a companion diagnostic test for use with tamibarotene as a result of the failure of the Company’s SELECT-MDS-1 Phase 3 trial evaluating tamibarotene to meet its primary endpoint of complete response rate, which was previously disclosed on the Company’s Current Report on Form 8-K filed with the U.S. Securities and Exchange Commission (the "SEC") on November 13, 2024 (Filing, 8-K, Syros Pharmaceuticals, NOV 18, 2024, View Source [SID1234648478]). The termination will be effective 90 days following such notice.

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Under the terms of the Agreement, QIAGEN was responsible for developing, and obtaining and maintaining regulatory approvals for the companion diagnostic test in the United States and, at the request of the Company and subject to the negotiation of mutually agreed payments, in certain additional markets. In addition, QIAGEN had agreed to use commercially reasonable efforts to manufacture the companion diagnostic test and, upon negotiation of mutually agreed terms, to make the companion diagnostic test commercially available in the United States, the additional markets, and such other countries as the parties may mutually agree. In connection with the termination of the Agreement, the Company will be obligated to pay QIAGEN certain wind-down and other costs and other final payments.

The foregoing description of the material terms of the Agreement is qualified in its entirety by reference to the complete text of the Agreement, which the Company has filed, with confidential terms redacted, with the SEC as Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2022.

Item 2.04.
Triggering Events That Accelerate or Increase a Direct Financial Obligation or an Obligation under an Off-Balance Sheet Arrangement.

As previously disclosed in the Company’s Current Report on Form 8-K filed with the SEC on November 13, 2024, an event of default occurred on November 12, 2024 under the Loan and Security Agreement dated February 12, 2020 (as subsequently amended, the "Loan Agreement") between the Company and Oxford Finance LLC ("Oxford"), as a result of the failure of the Company’s SELECT-MDS-1 Phase 3 trial evaluating tamibarotene to meet its primary endpoint of complete response rate (the "Trial Results Default").

The Loan Agreement provides Oxford, as collateral agent, with the right, upon such an event of default, to exercise remedies against the Company and the collateral securing the loans under the Loan Agreement, including the right to declare all obligations of the Company under the Loan Agreement immediately due and payable and the right to foreclose against the Company’s cash and other property securing the Loan Agreement obligations. Pursuant to the Loan Agreement, a $20.0 million term loan was funded to the Company on February 12, 2020 and another $20.0 million term loan was funded to the Company on December 23, 2020. The floating annual rate for each term loan is equal to the greater of (i) 7.75% and (ii) the sum of (a) the 1-month CME Term SOFR reference rate, (b) 0.10%, and (c) 5.98%. Pursuant to the terms of an amendment dated May 9, 2024 (the "Fourth Loan Amendment"), Oxford agreed to extend the interest-only period from September 1, 2024 to November 1, 2025, and to provide for the repayment of the aggregate outstanding principal balance of the term loan in monthly installments starting on November 1, 2025 through February 1, 2028 (the "Maturity Date"). In connection with a prior extension of the interest-only period, the Company agreed to pay fees of $300,000 upon the first to occur of the Maturity Date or the acceleration or prepayment of any term loan. In connection with the Fourth Loan Amendment, the Company agreed to pay an additional fee of $1,050,000 upon the first to occur of the Maturity Date or the acceleration or prepayment of any term loan. The Company is also required to make a final payment equal to 5.00% of the amount of the term loan drawn upon the first to occur of the Maturity Date or the acceleration or prepayment of any term loan. If the term loans are accelerated following the occurrence of an event of default, the Company must also pay a prepayment fee equal to 0.50% of the amount of the outstanding term loans. The foregoing description of the Loan Agreement is qualified in its entirety by reference to the full text of the Loan Agreement which is filed as Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and incorporated herein by reference.

On November 14, 2024, the Company received written notice from Oxford of the Trial Results Default, which notice declared all of the Loan Agreement obligations immediately due and payable and demanded the immediate repayment of approximately $43.7 million in satisfaction of all obligations under the Loan Agreement (the "Default Notice").

On November 15, 2024, the Company paid $33.5 million to Oxford in partial satisfaction of its obligations under the Loan Agreement. The Company intends to negotiate and enter into a forbearance agreement with Oxford that will further address the Trial Results Default and the Default Notice.