On June 22, 2020 Forbius, a clinical-stage protein engineering company that develops biotherapeutics to treat cancer and fibrosis, reported that it will participate at SVB Leerink’s inaugural Biopharma Private Company Connect July 7th-9th, 2020 (Press release, Forbius, JUN 22, 2020, View Source [SID1234561276]).

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On June 22, 2020 Rakuten Medical, Inc. (Rakuten Medical) reported the results of two preclinical studies presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting II (Press release, Rakuten Medical, JUN 22, 2020, View Source [SID1234561303]). These studies further demonstrate the mechanism of action of Rakuten Medical’s Illuminox technology platform with its antibody-IRDye 700DX conjugate and how this unique technology induces tumor cells and enhances the adaptive immune response.

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"We are excited to present data on the mechanism of action of the Illuminox technology to induce rapid cell membrane disruption of cells targeted with the antibody-IRDye 700DX conjugate and the induction of cell necrosis and immunogenic cell death," said Miguel Garcia-Guzman, Ph.D., Chief Scientific Officer, Rakuten Medical. "Consistent with this mechanism of action, the study also shows that Illuminox treatments induce robust anti-cancer effects in immunocompetent animals by activating tumor specific innate and adaptive anticancer immunity with long term immune memory."

The following preclinical poster presentations were showcased during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting II:

"Molecular mechanism of action of photoimmunotherapy with antibody-IR700 dye conjugates: Role of singlet oxygen in cell membrane disruption and necrotic cell death." (Abstract 480), presented by Roger Heim, Rakuten Medical.

This poster investigates the mechanism of action of Rakuten Medical’s proprietary Illuminox photoimmunotherapy through a series of preclinical experiments. These data describe the unique biophysical processes by which photoimmunotherapy with antibody-IR700 dye damages cell membranes and induces cell death.

"Anticancer activity by photoimmunotherapy is driven by adaptive immune responses and induces vaccinal effects in mice." (Abstract 949), presented by C. Daniel De Magalhaes Filho, Rakuten Medical.

This poster confirms previous data demonstrating that photoimmunotherapy induces cell death in tumor cells and ignites an immune response against the tumor [Hsu M, et al. AACR (Free AACR Whitepaper) 2019].

In this study, mice implanted with photoimmunotherapy-treated tumor cells rejected new tumor challenges, indicating that photoimmunotherapy induces immunogenic cell death and activates immune responses in the host mice protecting against future tumor challenges.

On June 22, 2020 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported the company will receive a $10 million milestone payment from Janssen Biotech, Inc. (Janssen) triggered under the Collaboration and License Agreement between the two companies (Press release, Halozyme, JUN 22, 2020, View Source [SID1234561320]). The milestone payment is associated with the first commercial sale in the European Union of Janssen’s subcutaneous formulation of DARZALEX (daratumumab) utilizing ENHANZE, which was recently granted marketing authorization by the European Commission.

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On June 22, 2020 Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported that updated pharmacodynamic and safety data at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, occurring June 22 – 24, 2020 (Press release, Exicure, JUN 22, 2020, View Source [SID1234561336]).

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The AACR (Free AACR Whitepaper) poster, titled "Phase 1b/2 Study of an Intratumoral TLR9 Agonist Spherical Nucleic Acid (AST-008) and Pembrolizumab: Evidence of Immune Activation," is presenting new preliminary pharmacodynamic and safety data of cavrotolimod (AST-008), alone and in combination with pembrolizumab, from Exicure’s ongoing Phase 1b/2 clinical trial (ClinicalTrials.gov identifier: NCT03684785). Cavrotolimod (AST-008) is a novel SNA configuration of a toll-like receptor 9 (TLR9) agonist oligonucleotide, designed to trigger anti-tumor immune responses.

Gene expression analysis data from patient tumor biopsies demonstrated increases in leukocytes in injected tumors after intratumoral (IT) cavrotolimod (AST-008) alone and in combination with pembrolizumab versus baseline. Uninjected tumors also showed increased immune cell levels after patients received cavrotolimod (AST-008) and pembrolizumab, suggesting immune cell trafficking.

Dose-dependent activation of key immune cells, including cytotoxic T cells and natural killer cells, as well as increases in cytokine/chemokine levels were observed in patient blood after IT cavrotolimod (AST-008) treatment alone, and cavrotolimod (AST-008) plus pembrolizumab treatment. We expect that activation of these cell types and expression of immune system signaling proteins may help produce anti-tumor effects.

Cavrotolimod (AST-008) was well-tolerated, with a safety profile consisting primarily of injection site reactions and flu-like symptoms, which is believed to reflect local and systemic immune activation. No cavrotolimod (AST-008)-related serious adverse events or dose limiting toxicity have been reported.

Using these data, a recommended Phase 2 dose of 32 mg cavrotolimod (AST-008) has been identified for the Phase 2 portion of the clinical trial now underway, where cavrotolimod (AST-008) will be given in combination with pembrolizumab or cemiplimab for the treatment of locally advanced or metastatic Merkel cell carcinoma or cutaneous squamous cell carcinoma, respectively, in patients with progression despite approved anti-PD-(L)1 therapy.

This poster is being presented during the AACR (Free AACR Whitepaper) Virtual Meeting II in the session Late-Breaking Research: Clinical Research 1 / Endocrinology under abstract number LB-140. The poster will be available for viewing from June 22 – 24.

On June 22, 2020 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported preclinical data for its next generation anti-folate receptor alpha (FRα) ADC, IMGN151, which is being investigated in tumors with a broad range of FRα expression (Press release, ImmunoGen, JUN 22, 2020, View Source [SID1234561352]). The findings were shared via poster presentation at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting II.

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"Engineered to include multiple antibody and linker-payload innovations, IMGN151 targets tumors with a broad range of FRα expression," said Eric Westin, MD, Vice President of Clinical Development and Translational Sciences at ImmunoGen. "IMGN151 demonstrated enhanced anti-tumor activity in both in vitro and in vivo preclinical models, with complete regression of human tumor xenograft models induced in those with high, medium, and low levels of FRα expression. Based on these data, we look forward to exploring IMGN151 in the clinic in multiple FRα-positive epithelial malignancies, including ovarian, endometrial, triple negative breast, and non-small cell lung cancer."

IMGN151 PRECLINICAL DATA
Poster Presentation, Abstract 2890

IMGN151 comprises an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FRα, linked to a highly potent maytansinoid derivative, DM21, via a cleavable peptide linker with enhanced stability, longer half-life, and increased bystander activity. The average drug per antibody ratio is 3.5. IMGN151 activity was characterized against cell lines and xenograft models with a wide range of FRα expression and compared to mirvetuximab soravtansine (IMGN853). Cell lines and xenograft models originated from ovarian, endometrial, breast, and cervical cancer.

Key findings include:

The protease-cleavable linker deployed in IMGN151 improves stability and ADC exposure; as compared to IMGN853, pharmacokinetic studies in cynomolgus monkeys showed increased ADC half-life by 60 hours and conjugate exposure in vivo by 40%.
The IMGN151 biparatopic format boosted antibody binding events and DM21 payload delivery in tumor cell lines; the increased payload delivery and greater membrane permeability of DM21 enhanced bystander killing activity.
In vitro, IMGN151 was more active against FRα-positive cell lines, with the most pronounced effect in cells with low to medium levels of FRα.
In vivo, IMGN151 demonstrated better activity over IMGN853 against low and medium levels of FRα, and equivalent activity to IMGN853 against FRα high tumors with lower effective dose; all tested doses were well tolerated.
Additional information can be found at www.aacr.org.

ABOUT IMGN151

IMGN151 is a next-generation ADC, designed to address the unmet needs of cancer patients with tumor types expressing lower levels of folate receptor alpha (FRα). IMGN151 comprises an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FRα, linked to a highly potent maytansinoid derivative, DM21, via a cleavable peptide linker with enhanced stability, longer half-life, and increased bystander activity.