On November 14, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported the presentation of new data from EFTISARC-NEO, a Phase II investigator-initiated trial of eftilagimod alpha (efti) in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS), at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting (Press release, Immutep, NOV 14, 2024, View Source [SID1234648305]). Based on preliminary analysis among 21 patients available for primary endpoint assessment, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS.

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Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO (Warsaw) and the trial’s principal investigators, stated: "Our belief in efti’s unique mechanism of action to complement radiotherapy and pembrolizumab in order drive better outcomes for patients with this rare aggressive disease was the foundation of the EFTISARC-NEO trial. These very encouraging results we are presenting today build our confidence in the synergistic effects of this new therapeutic approach and its potential to treat these patients in dire need of more effective therapies. In particular, the high level of hyalinization/fibrosis achieved with this novel combination therapy, three-times above historical results from standard radiotherapy, demonstrates remarkable efficacy in patients with resectable soft tissue sarcomas."

In the neoadjuvant setting for patients with resectable STS, the combination achieved a greater than threefold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgical resection as compared to a historical median 15% from standard radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosisrate has also been identified as an important predictor of overall survival for STS patients.

The EFTISARC-NEO trial, with a data cut-off of 20 October 2024, also showed 71.4% of patients achieved a pathologic response defined as ≥35% of hyalinization/fibrosis and 9.5% of patients achieved a complete pathologic response. The triple combination therapy is safe with no grade ≥3 toxicities related to efti and pembrolizumab.

Dr. Frédéric Triebel, CSO of Immutep, said: "We are pleased with the strength of these preliminary results in this difficult-to-treat cancer. To see 71.4% of soft tissue sarcoma patients achieving a pathologic response defined as ≥35% of hyalinization/fibrosis combined with low viable tumour cells at 8% is very promising, especially as strong efficacy has been observed in different STS subtypes. We look forward to further evaluation of efti’s potential as neoadjuvant immunotherapy to help drive improved clinical outcomes.

The ongoing open-label EFTISARC-NEO Phase II study, conducted by the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, is expected to reach the planned enrolment of 40 patients in Q1 CY2025. The trial is primarily funded with an approved grant from the Polish government awarded by the Polish Medical Research Agency program. For more information, visit clinicaltrials.gov (NCT06128863)

On November 13, 2024 GSK plc (LSE/NYSE: GSK) reported positive headline results from a planned interim analysis of the DREAMM-7 head-to-head phase III trial evaluating Blenrep (belantamab mafodotin) in combination with bortezomib plus dexamethasone (BorDex) as a second-line or later treatment for relapsed or refractory multiple myeloma (Press release, GlaxoSmithKline, NOV 14, 2024, View Source [SID1234648299]). The trial met the key secondary endpoint of overall survival (OS), showing that belantamab mafodotin when combined with BorDex significantly reduced the risk of death versus standard of care daratumumab plus BorDex.

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "The overall survival results from the DREAMM-7 trial underscore the potential for this Blenrep combination to extend the lives of patients with relapsed/refractory multiple myeloma. This is a statistically significant and clinically meaningful advancement for patients and potentially transformative for treatment. We look forward to sharing these data with health authorities and presenting the full results at next month’s American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting."

Results from the interim analysis, including safety data, will be presented at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on 9 December 2024 at 11:15 a.m. PT.

The DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development programme continues to evaluate the potential of belantamab mafodotin in early lines of treatment and in combination with novel therapies and standard of care treatments. In addition to DREAMM-7, this includes the ongoing head-to-head phase III DREAMM-8 trial evaluating belantamab mafodotin in combination with pomalidomide and dexamethasone versus bortezomib in combination with pomalidomide and dexamethasone.

A phase III study in newly diagnosed transplant ineligible multiple myeloma is expected to be initiated by the end of 2024 as part of the DREAMM programme.

In 2024, belantamab mafodotin combinations have been filed in the US, European Union1, Japan2, United Kingdom, Canada and Switzerland for the treatment of relapsed or refractory multiple myeloma based on the results of the DREAMM-7 and DREAMM-8 trials. In China3, the National Medical Products Administration has granted Breakthrough Therapy Designation for belantamab mafodotin in combination with BorDex, as well as priority review for the regulatory application based on the results of DREAMM-7.

About DREAMM-7
The DREAMM-7 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with BorDex compared to a combination of daratumumab and BorDex in patients with relapsed/refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy.

A total of 494 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin in combination with BorDex or a combination of daratumumab and BorDex. Belantamab mafodotin was scheduled to be dosed at 2.5mg/kg intravenously every three weeks.

The primary endpoint is PFS as per an independent review committee. The key secondary endpoints include OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

Results from DREAMM-7 were first presented4 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024, shared in an encore presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and published in the New England Journal of Medicine.

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.5,6 There are approximately more than 180,000 new cases of multiple myeloma diagnosed globally each year.7 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.8

About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Blenrep is approved as monotherapy in Hong Kong, Israel and Singapore. Refer to the local Summary of Product Characteristics for a full list of adverse events and complete important safety information.

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.

On November 13, 2024 TAE Life Sciences (TLS), a leader in developing boron neutron capture therapy (BNCT) technology and associated innovative boron target drugs, and Stella Pharma, the pioneering developer of boronophenylalanine (BPA) under the product name, Steboronine, for BNCT, are pleased to announce a strategic collaboration focused on the development, commercialization and expansion of BNCT using BPA in the United States and European markets (Press release, TAE Life Sciences, NOV 13, 2024, View Source [SID1234648415]).

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Stella Pharma’s BPA drug is the world’s first and only clinically approved boron drug for BNCT, marking a breakthrough in cancer treatment. Japan became the first country to approve BNCT for the treatment of head and neck cancers, using Stella Pharma’s pioneering BPA drug. Now, Stella Pharma, as the leading producer and supplier of BPA, has joined forces with TAE Life Sciences to expand the adoption of BNCT worldwide.

Supporting the Future of BNCT Therapy

The collaboration objectives include extensive international cooperation in the development and commercialization of BNCT and BPA across the USA and Europe with clinical trials anticipated to begin in 2026. TLS will serve as the exclusive commercial partner for Stella Pharma’s BPA in these regions, representing a significant expansion of BNCT accessibility outside of Asia.

"Our partnership with Stella Pharma combines our shared commitment to advancing BNCT as a viable cancer treatment for patients worldwide," said Rob Hill, CEO of TAE Life Sciences. "We are excited to bring the proven benefits of BPA to U.S. and European healthcare institutions and to support BNCT globally with this powerful therapeutic solution."

Both companies have also committed to supporting BNCT equipment vendors across all markets in implementing BPA-based BNCT treatments. By fostering partnerships within the BNCT ecosystem, TLS and Stella Pharma aim to enhance the clinical reach of BNCT in treating recurrent head and neck cancers and advancing clinical studies for other cancers, including brain, skin, breast, esophagus, and lung cancers.

"Our alliance with TAE Life Sciences marks a significant step in expanding the reach of BPA-based BNCT treatments beyond Asia," said Koki Uehara, President and Chief Operating Officer of Stella Pharma. "We look forward to collaborating internationally to develop and commercialize BNCT and aim to deliver this advancing cancer treatments to patients and their families worldwide."

Exploring Future Opportunities Together

Stella Pharma and TAE Life Sciences share a vision of advancing BNCT treatment for hard-to-treat cancers and pledge to explore additional areas for collaboration. Through this alliance, they seek to accelerate innovation, expand treatment options, and ultimately improve outcomes for cancer patients worldwide.

For more information about TAE Life Sciences, Alphabeam, and the company’s proprietary boronated BNCT drugs, please visit taelifesciences.com.

On November 13, 2024 Reverb Therapeutics, a leader harnessing the body’s immune system and cytokine signaling to treat life-threatening diseases, reported it has launched a collaboration with Royalmount Laboratories, based in Montreal, as Reverb works towards lead selection and pre-IND enabling work on its first drug candidate (Press release, Royalmount Laboratories, NOV 13, 2024, View Source [SID1234648314]).

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Royalmount Laboratories is one of Canada’s premier CRO organizations, supporting biopharma and pharma companies with their bioanalytical needs to advance their discovery, preclinical and clinical programs. It is rapidly becoming the leading niche small and large molecule bioanalytical CRO in Canada.

"As we move towards the start of clinical trials in about 18 months’ time, we needed a scientific partner that could assist with toxicity studies, scale-up of manufacturing, and a variety of CMC tasks to ensure that our drug candidate moves swiftly from the lab to the clinic," said David de Graaf, Ph.D., CEO of Reverb Therapeutics. "We are impressed with Royalmount Laboratories’ capabilities and the quality of their staff."

Adrien Musuku, Senior Director of biopharmaceutics for Royalmount Laboratories, said, "At Royalmount Laboratories, we provide both small and large molecule bioanalytical support needed to bring life-changing therapies to those in need. Our proven track record of strong science, unmatched quality and consistent on-time delivery facilitates quick advancement in the development of new therapeutic entities. We are proud to support companies like Reverb Therapeutics, an early-stage firm with novel science and a unique approach to harnessing the power of cytokines to treat disease. Reverb Therapeutics is a perfect example of the kind of dynamic company we want to help advance to the clinic and beyond."

Terms of the collaboration were not disclosed. Development work for Reverb begins immediately.

Reverb’s novel Amplify•R platform combines bispecific antibody engineering with data-driven modelling of antibody-tissue interaction to amplify endogenous cytokines and redirect them to tissues of interest. This approach avoids the hurdles that have blocked other attempts to enlist cytokines to treat disease, which include systemic toxicity, immunogenicity, and manufacturing issues. Reverb Therapeutics is developing its precision medicine for the immune system with a focus on the treatment of cancer and auto-immune diseases.

The Amplify•R platform is designed to expand the therapeutic window of cytokines by harnessing the body’s own endogenous cytokines and amplifying their activity in a tissue-specific manner, leading to profound disease-modifying effects. The Amplify•R platform is a modular, plug-and-play, IgG-based platform, enabling rapid pre-clinical testing and ease of manufacturing for scale-up and clinical utility.