On June 27, 2023 Mestag Therapeutics (‘Mestag’), an immunotherapy company focusing on fibroblast-immune interactions, and VIB, the leading life science research institute in Flanders, reported entering into an agreement under which Mestag obtains the exclusive worldwide rights to research, develop and commercialize a panel of single domain antibodies, also known as Nanobodies, to an undisclosed target that plays a central role in anti-cancer immunity (Press release, Mestag Therapeutics, JUN 27, 2023, View Source [SID1234632943]).

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Under the terms of the agreement, Mestag will be responsible for the research, development and commercialization of the antibodies, which are the outcome of many years of leading-edge research within VIB. In return, VIB will receive an upfront payment, future success-based milestones and royalty payments.

Susan Hill, PhD, Chief Executive Officer of Mestag Therapeutics, said, "We are delighted to partner with VIB, one of the premier research institutes in Europe and a leader in nanobody technology and cancer biology. This agreement further strengthens Mestag’s first-in-class pipeline and targets an exciting new area of fibroblast-immune cancer biology."

"We are thrilled to work with Mestag. Mestag brings together a unique expertise set in fibroblast-immune biology and a deep understanding of antibody engineering and development. The company is perfectly positioned to take this promising program forward," said Jérôme Van Biervliet, PhD, Managing Director of VIB.

On June 27, 2023 ImmunoGenesis, a clinical-stage biotechnology company developing science-driven immune therapies, and Cancer Focus Fund, LP, a unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center to provide funding and clinical expertise to advance promising cancer therapies, reported that Cancer Focus Fund plans to invest $4.5 million to support the Phase 1a/1b clinical trial of ImmunoGenesis’ lead candidate, IMGS-001 (Press release, ImmunoGenesis, JUN 27, 2023, View Source [SID1234632942]). IMGS-001 is a dual-specific PD-L1/PD-L2 antibody designed to treat immune-excluded tumors, which are resistant to existing immunotherapy. The investment will support the portion of the IMGS-001 Phase 1a/1b multi-site clinical trial being conducted at MD Anderson. It coincides with ImmunoGenesis’ Series A financing, which is expected to close in the third quarter.

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"Overcoming the widespread resistance to immunotherapy in immune-excluded tumors requires re-envisioning the starting point for treatment," said Dr. Michael A. Curran, Founder of ImmunoGenesis. "We are addressing this challenge by developing a novel, dual–specific PD–L1/PD–L2 inhibitor engineered to include tumor-killing effector function – essentially addressing tumor pathology at the roots. Based on the results of preclinical studies, we believe that IMGS–001 has the potential to significantly improve clinical response over currently approved checkpoint inhibitors for patients with immune-excluded tumors."

IMGS-001 is based on discoveries made by the laboratory of Dr. Curran, Associate Professor of Immunology at MD Anderson, and by the Oncology Research for Biologics & Immunotherapy Translation (ORBIT) platform, part of MD Anderson’s Therapeutics Discovery division. The technology was licensed to ImmunoGenesis in 2019.

"The Cancer Focus Fund Scientific Advisory Board is made up of expert scientists and clinicians and to be recommended for an investment by this group is an honor that we believe provides validation of the clinical potential for IMGS-001," said James Barlow, ImmunoGenesis President and CEO. "We believe that IMGS-001 has the potential to become the foundational treatment for immune-excluded tumors where there is both significant unmet need and tremendous market opportunity. This funding, combined with our upcoming Series A financing, will provide the opportunity to establish the initial proof of concept for this groundbreaking approach and bring hope, and potentially life-saving treatments, to the patients battling these difficult tumors."

"Cancer Focus Fund was founded with the goal of assuring that innovative early-stage cancer therapies had the opportunity to undergo the rigorous clinical testing needed for advancement," said Ross Barrett, a founder and Managing Partner of Cancer Focus Fund. "We are thrilled at the opportunity to invest in the exciting new approach to cancer immunotherapy pioneered by Dr. Curran – our first investment in a discovery made at MD Anderson and developed by a biotechnology company located here in Houston. Immune-excluded tumors are thought to represent more than half of all cancers and contribute to the high failure rates that limit the potential of cancer immunotherapy for too many patients. We welcome the opportunity to support ImmunoGenesis by investing in this promising candidate and look forward to the results of this important clinical trial."

About the IMGS-001 Phase 1a/1b Clinical Trial
This funding will support a Phase 1a/1b, first-in-human, open-label, dose-escalation and dose–expansion study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of IMGS-001. Phase 1a is a dose-escalation study that aims to determine the safety, tolerability, and maximum tolerated dose (MTD) of IMGS-001 in adult patients with locally advanced or metastatic solid tumors refractory to appropriate standard of care treatments. Phase 1b is an open-label, dose-expansion cohort study of patients with prespecified tumors intended to further assess the safety and preliminary antitumor activity of IMGS-001. Dr. David S. Hong, Professor of Investigational Cancer Therapeutics at MD Anderson, will serve as Principal Investigator of the trial.

About IMGS-001, a PD-L1/PD-L2 Dual-Specific Inhibitor
IMGS-001, the lead program at ImmunoGenesis, is a PD-L1/PD-L2 dual-specific inhibitor with engineered cytotoxic effector function. IMGS-001 is the first molecule to target PD-L2 in addition to PD-L1. This means that IMGS-001 has the potential to shut down the entire PD-1 pathway and provide a superior blockade compared to other PD-1 or PD-L1 inhibitors. The engineered effector function enables IMGS-001 to kill immunosuppressive PD-L1- and/or PD-L2-expressing cells present in the tumor microenvironment, which may enable it to overcome immune resistance in immune-excluded tumors. Preclinical data showed that IMGS-001 drove substantially higher response rates in head-to-head studies vs. currently available immunotherapies. With its innovative multi-tasking mechanism of superior blockade and killing function, IMGS-001 may provide a new foundation for combination therapies.

On June 27, 2023 CoImmune, Inc., a clinical stage immuno-oncology company working to redefine cancer treatment using best-in-class cellular immunotherapies, reported that it has exercised its option to obtain an exclusive license in the Delta-like Ligand 3 (DLL3)-targeted, allogeneic Chimeric Antigen Receptor-Cytokine Induced Killer (CAR-CIK) cell therapy field to interleukin-18 (IL-18) Armored CAR technology under a prior agreement with Memorial Sloan Kettering Cancer Center (MSK) (Press release, CoImmune, JUN 27, 2023, View Source [SID1234632941]). The company is coupling the technology with allogeneic CIK cells and launched a development program focused on solid tumors with initial trials planned in small cell lung cancer (SCLC).

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"Traditional CAR T cells have proven to be poorly effective against solid tumors due, in part, to the immunosuppressive tumor microenvironment, but we have demonstrated the potential for CAR-CIK cells to be effective in combination with additional technologies that may be able to improve proliferation, persistence and reverse immunosuppression," said Charles Nicolette, Ph.D., Chief Executive Officer of CoImmune. "IL-18 expression has the potential to greatly enhance the potency of DLL3-targeted therapy and we look forward to advancing our development of CMN-009, an IL-18 armored anti-DLL3 CAR-CIK therapeutic for SCLC."

CoImmune has the option to select up to three targets for IL-18 CAR products in the allogeneic cell therapy field under the agreement with MSK. In March 2023, the company announced it had selected CD19 as the first target to support the clinical development of CMN-008 (Armored CAR-CIK cells) in B-cell malignancies. CoImmune plans to file an Investigational New Drug (IND) application for CMN-008 to treat acute lymphoblastic leukemia (ALL) this year.

The DLL3 target has been identified as a tumor-specific cell surface marker on neuroendocrine cancers including SCLC. A paper recently published in Journal of Clinical Investigation, titled, "IL-18-secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models," describes an effort by researchers including Renier J. Brentjens, M.D., Ph.D., Deputy Director and Chair of Medicine, Roswell Park Comprehensive Cancer Center, to develop a CAR against DLL3 that displays antitumor efficacy in xenograft and murine SCLC models. The data reported show IL-18 armored CAR-DLL3 T cells could eradicate disease at very low doses, especially when combined with a PD-1 checkpoint inhibitor.

"Our preclinical studies with a model of metastatic SCLC demonstrated that IL-18 production increased the activation of both CAR T cells and endogenous tumor-infiltrating lymphocytes," said Dr. Brentjens, who previously developed the IL-18 Armored CAR technology at MSK. "We also observed increased infiltration, repolarization and activation of antigen-presenting cells. Human IL-18-secreting anti-DLL3 CAR T cells were able to eradicate disease at dose levels where standard anti-DLL3 CAR-T cells were ineffective. We saw strong synergy with PD1 checkpoint inhibition, suggesting a potential for curative responses at lower, subtherapeutic administrations of IL-18 armored anti-DLL3 CAR T cells. These results define DLL3-targeting CAR T cells that produce IL-18 as a promising novel strategy against DLL3-expressing solid-tumor cancers."

CoImmune’s IL-18 armored CARCIK-DLL3 product prototype, CMN-009, will be studied in animal models throughout the remainder of 2023. Additional technologies licensed from MSK (e.g., SEAKER, SHIELD) will be tested in combination with CMN-009 to further enhance functionality. The Company expects to initiate IND-enabling studies in the first half of 2024.

On June 27, 2023 AVEO Oncology, an LG Chem company, ("AVEO"), announced today that it has completed enrollment in the pivotal Phase 3 TiNivo-2 study in patients with advanced relapsed or refractory renal cell carcinoma (RCC) following prior immunotherapy exposure. The study is evaluating FOTIVDA (tivozanib) in combination with OPDIVO (nivolumab), Bristol Myers Squibb’s anti-PD-1 immunotherapy. FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for the treatment of adult patients with RCC following two or more prior systemic therapies.

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There are currently no National Comprehensive Cancer Network (NCCN) Category 1 recommended agents for patients with advanced RCC who were previously treated with prior immunotherapy. All currently available treatment options for advanced RCC were approved based on clinical studies conducted prior to the introduction of frontline immunotherapy combinations. There is an unmet need to improve the understanding of treatment sequencing and provide new treatment regimens for advanced RCC.

The randomized, controlled, open-label TiNivo-2 Phase 3 study enrolled patients with RCC who have progressed following prior immunotherapy treatment. Patients were randomized 1:1 to receive either low dose FOTIVDA in combination with OPDIVO or standard dose FOTIVDA alone. The TiNivo-2 study’s primary endpoint is progression free survival, with key secondary endpoints to include overall survival, overall response rate, duration of response and safety.

The TiNivo-2 study enrolled across clinical sites in the United States, Canada, Mexico, Europe and South America. "We are very excited to have achieved this interim milestone in the TiNivo-2 study and we are grateful to our global investigators, our AVEO development staff, and especially to the patients who are participating in the study. The TiNivo-2 study addresses an important question in the treatment of RCC, and we continue to work diligently to deliver the study results once data mature," said AVEO’s Chief Medical Officer, Dr. Martin Birkhofer.

"The TiNivo-2 study will provide us with a robust Phase 3 dataset to answer the outstanding question of whether adding a PD-1 Inhibitor (nivolumab) to a VEGF TKI (tivozanib), provides additional efficacy and acceptable safety over a single agent VEGF TKI following prior immunotherapy," said Toni Choueiri, M.D., Director, Lank Center for Genitourinary Oncology; Director, Kidney Cancer Center; Jerome and Nancy Kohlberg Chair and Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute. "TiNivo-2 is a particularly important study for understanding appropriate sequencing strategies for RCC patients following immunotherapy given the presentation at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting of the CONTACT-03 study where adding a PD-L1 inhibitor (atezolizumab) to full dose cabozantinib failed to show a benefit over cabozantinib alone in RCC patients treated with prior immunotherapy."

The Company expects to share initial results from the TiNivo-2 study when the data mature, which is anticipated in the second half of 2024.

About FOTIVDA (tivozanib)

FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models.4 FOTIVDA was discovered by Kyowa Kirin.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTION

Hypertension and Hypertensive Crisis: Control blood pressure prior to initiating FOTIVDA. Monitor for hypertension and treat as needed. For persistent hypertension despite use of anti-hypertensive medications, reduce the FOTIVDA dose.

Cardiac Failure: Monitor for signs or symptoms of cardiac failure throughout treatment with FOTIVDA.

Cardiac Ischemia and Arterial Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe arterial thromboembolic events, such as myocardial infarction and stroke.

Venous Thromboembolic Events: Closely monitor patients who are at increased risk for these events. Permanently discontinue FOTIVDA for severe venous thromboembolic events.

Hemorrhagic Events: Closely monitor patients who are at risk for or who have a history of bleeding.

Proteinuria: Monitor throughout treatment with FOTIVDA. For moderate to severe proteinuria, reduce the dose or temporarily interrupt treatment with FOTIVDA.

Thyroid Dysfunction: Monitor before initiation and throughout treatment with FOTIVDA.

Risk of Impaired Wound Healing: Withhold FOTIVDA for at least 24 days before elective surgery. Do not administer for at least 2 weeks following major surgery and adequate wound healing. The safety of resumption of FOTIVDA after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Discontinue FOTIVDA if signs or symptoms of RPLS occur.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

Allergic Reactions to Tartrazine: The 0.89 mg capsule of FOTIVDA contains FD&C Yellow No.5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥5%) were sodium decreased, lipase increased, and phosphate decreased.

DRUG INTERACTIONS

Strong CYP3A4 Inducers: Avoid coadministration of FOTIVDA with strong CYP3A4 inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise not to breastfeed.
Females and Males of Reproductive Potential: Can impair fertility.
Hepatic Impairment: Adjust dosage in patients with moderate hepatic impairment. Avoid use in patients with severe hepatic impairment.

To report SUSPECTED ADVERSE REACTIONS, contact AVEO Pharmaceuticals, Inc. at 1-833-FOTIVDA (1-833-368-4832) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FOTIVDA Full Prescribing Information which is available at www.AVEOoncology.com.

On June 27, 2023 Independent biopharmaceutical company Specialised Therapeutics (ST) reported that a new therapy to treat the most common type of non-Hodgkin lymphoma in adults – diffuse large B-cell lymphoma – is now approved for use in Australia (Press release, Specialised Therapeutics Asia, JUN 27, 2023, View Source [SID1234632939]).

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The Therapeutic Goods Administration (TGA) has provisionally approved MINJUVI (tafasitamab) "in combination with lenalidomide followed by MINJUVI monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT)".[1]

Australian lymphoma specialist and current chair of the Australasian Lymphoma Alliance, Professor Chan Cheah, said the MINJUVI approval was a great step forward for patients who had been diagnosed with DLBCL and relapsed, as the MINJUVI regimen provides an opportunity for longer-term disease management.

"I think it is great news for patients," Professor Cheah said. "We do have chemotherapy options and we cure about two-thirds of patients using that approach. Unfortunately, a substantial proportion of patients either don’t respond to chemotherapy, or the disease comes back after chemotherapy, and they need better treatments."

MINJUVI, a CD19-targeting immunotherapy that works by attaching to a protein on the surface of B-cell lymphoma cells, stimulating an immune response against the lymphoma, is also approved in the United States [as Monjuvi (tafasitamab-cxix)], Great Britain, Canada, Europe and other countries.

Professor Cheah added: "Access to novel immune therapies like MINJUVI is really important for Australian patients. Apart from CAR-T cell therapies – and these are only applicable to a certain proportion of patients with DLBCL – there have been no novel therapies for relapsed DLBCL approved in Australia. MINJUVI has a favourable side effect profile and (combined with lenalidomide) has demonstrated a high response rate in patients with relapsed disease. We now need to see it listed on the Pharmaceutical Benefits Scheme."

MINJUVI has been approved via a provisional regulatory pathway, with the TGA participating in the Modified Project Orbis initiative to accelerate availability to Australian patients. The approval was based on data from the Phase 2 L-MIND study, an open label, multi-center single arm study which evaluated its safety and efficacy in combination with lenalidomide as a treatment for patients with relapsed or refractory DLBCL who were not eligible for ASCT.[1,3]

Continued approval for this indication depends on verification and description of clinical benefit in the confirmatory Phase 3 frontMIND study which has completed enrollment.[4]

Recently, five-year follow up data were presented which showed that MINJUVI plus lenalidomide followed by MINJUVI monotherapy provided prolonged, durable responses in adult patients with relapsed or refractory DLBCL. The overall response rate (ORR) was 57.5% with a complete response (CR) observed in 41.2% of patients, and a partial response (PR) in 16.2% of patients. The median overall survival was 33.5 months and median progression-free survival (PFS) was 11.6 months.[2] The most common adverse reactions with MINJUVI are infections (73%), neutropenia (51%), asthenia (40%), anaemia (36%), diarrhoea (36%), thrombocytopenia (31%), cough (26%), oedema peripheral (24%), pyrexia (24%), decreased appetite (22%). The most common serious adverse reactions were infection (26%) including pneumonia (7%), and febrile neutropenia (6%).[1]

ST Chief Executive Officer Mr. Carlo Montagner said securing TGA approval was a key regulatory milestone for the company, noting that the therapy was synergistic with the company’s mission to provide therapies that addressed unmet needs in rare patient populations.

"We are delighted to successfully register MINJUVI for Australian patients and look forward to working with the lymphoma community to ensure it is available at the earliest opportunity," he said.

ST markets MINJUVI under an exclusive distribution arrangement with international partner Incyte (NASDAQ: INCY).