AACR 2017: Nine Presentations Feature ImmunoGen’s Approch to ADC development

Earlier today, ImmunoGen, a company at the forefront of antibody-drug conjugates (ADC-) development for the treatment of cancer, announced that nine abstracts highlighting the breath of the Company’s expertise in ADCs, will be presented at the upcoming annual meeting of the American Association of Cancer Research (AACR) to be held from April 1-5, 2017 in Washington D.C.

AACR Logo_NewsroomOver the last decades, ImmunoGen has built a large portfolio of ADC technologies, including alternative types of cancer-killing agents such as the company’s tubulin-acting maytansinoids and their DNA-acting IGNs as well as a variety of linker chemistries. This year, the presentations at AACR will cover a wide-array these innovations, including further advancements to linkers and payloads and novel targets for both solid tumors and hematological malignancies.


“…the data being presented at AACR further validates our full-spectrum of knowledge and leadership in this space…”


“ImmunoGen has an unmatched expertise and understanding of the core components of ADCs and the data being presented at AACR further validate our full-spectrum of knowledge and leadership in this space,” said Richard Gregory, Ph.D., ImmunoGen’s chief scientific officer. “ImmunoGen will be presenting nine abstracts at the conference with preclinical data demonstrating technology advances that will enable us to continue to drive innovation in ADC approaches.”

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Technology
ImmunoGen’s lead product candidate, mirvetuximab soravtansine, is in a Phase III trial for FRα-positive platinum-resistant ovarian cancer, and is in Phase Ib/II testing in combination regimens for earlier-stage disease.  The company’s technology is further used in ado-trastuzumab emtansine (Kadcyla®), an antibody-drug conjugate marketed and distributed by Genentech/Roche, in three other clinical-stage product candidates being developped by ImmunoGen, and in new drug development programs conducted in partnership with Amgen, Bayer, Biotest, CytomX, Lilly, Novartis, Sanofi and Takeda.

AACR 2017
Each year, the annual meeting of the American Association of Cancer Research highlights the best cancer science and medicine from institutions all over the world. Attendees are invited learn more detailed news about how to apply exciting new concepts, tools, and techniques in the development of novel anticancer drugs and introduce new ways in their own research.

AbstractTitleAuthorsDate &LocationDescription
Platform linker and payload innovations
# 75Comparison of site-specific and lysine-linked indolino-benzodiazepine antibody-drug conjugates (ADCs).Bai C, Nicholas C. Yoder NC,  Wilhelm A,  Adams S, Whiteman K, Lee J, O’Callaghan K, Maloney E, et al.April 2, 2017, 1:00-5:00 PM | Section 3While site-specific conjugation can lead to improved efficacy and tolerability, the advantages and disadvantages of site-specific conjugation should be carefully considered for every ADC candidate.
# 71Bystander activity and in vivo efficacy of a folate receptor α (FRα)-targeting antibody-drug conjugate with a novel peptide linker.Qiu Q, Wu R, Lanieri L, Maloney E, Skaletskaya A, Jin S, Wang L, Ab  O, et alApril 2, 2017, 1:00-5:00 PM | Section 3Folate receptor (FRα) is an antigen that is overexpressed on the cell surface of solid tumors including ovarian cancer. M9346A-NL-DM is a novel ADC, employing a new linker, with enhanced bystander activity and anti-tumor activity that can target tumors with heterogeneous expression of FRα.
 # 2186Peptide-cleavable maytansinoid (ADCs) induce high bystander killing leading to improved anti-tumor activity in vivo.Widdison WC, Costoplus JA, Ponte JF, Lanieri L, Setiady Y, Dong L, Skaletskaya A, Wu R, Qiu Q,  et al.April 3, 2017, 1:00 – 5:00 PM | Section 8A new promising type of maytansinoid ADC provides a high degree of bystander killing, improved activity in tumor models in vivo, and has a differentiated mechanism of metabolite release.
# 53Antibody-drug conjugates (ADCs) of peptide-linked Indolino-Benzodiazepine (IGN) DNA-alkylator provides improved anti-tumor activity over that of a crosslinker.Miller ML, Shizuka M, Ponte JF, Lanieri L, Vitharana D, Qiu Q, Reid EE, Archer KE, et al.April 2, 2017, 1:00-5:00 PM | Section 3Preclinical research shows that DNA-alkylating IGNs provide improved anti-tumor activity over that of a DNA-crosslinking ADC.
Preclinical research focused on novel targets
#37Novel antibody-drug conjugates targeting ADAM9-expressing solid tumors demonstrate potent preclinical activity.Hicks SW,  Yoder NC, Loo D, Muvaffak A,  Zhou Y, Fuller ME,  McShea MA,  Themeles  M, et al.April 2, 2017, 1:00-5:00 PM | Section 2ADAM9 is a promising cell surface target for antibody-drug conjugate development that is overexpressed in multiple solid tumor indications relative to corresponding normal tissues.
#38Target validation, antibody discovery and preclinical data supporting ADAM9 as an antibody-drug conjugate therapeutic target for solid tumors.Scribner JA, Barat B, Hicks SW,  Yoder NC, Son T, Widjaja L, Diedrich G, Gorlatov  S, et alApril 2, 2017, 1:00-5:00 PM | Section 2These data demonstrate that anti-ADAM9 ADCs exhibit antitumor activity against a broad panel of ADAM9-positive malignancies and cause durable remissions in preclinical models at doses expected to be clinically achievable. Anti-ADAM9 ADCs represent a promising therapeutic strategy to a wide range of ADAM9-expressing tumors.
#45In vitro and in vivo activity of a novel c-Met-targeting antibody-drug conjugate using a DNA-alkylating, indolinobenzodiazepine payload.Lai KC, Muvaffak A, Li M, Themeles M, Sikka S, Donahue K, Hicks SW, Romanelli A, Chittenden TApril 2, 2017, 1:00-5:00 PM | Section 2cMet dysregulation and/or overexpression are associated with tumor progression, metastasis and poor prognosis in numerous cancers. An anti-cMet antibody conjugated with the payload DGN549 exhibits compelling, c-Met targeted anti-cancer activity in vitro and in vivo, and represents a promising therapeutic strategy to deliver a potent cytotoxic agent to tumor cells bearing a wide range of c-Met expression.
Preclinical research focused on B-cell targets
#2651A novel CD19-targeting antibody-drug conjugate, huB4-DGN462, shows promising in vitro and in vivo activity in CD19-positive lymphoma models.Gaudio E, Tarantell C, Arribas AJ, Bordone RP,  Rinaldi A, Stussi G,  Zucca E, Rossi D, et al.April 3, 2017, 1:00 – 5:00 PM | Section 26CD19 is a cell surface membrane protein expressed in most mature and immature B cell neoplasms, which make it a promising target for ADC therapy for B cell malignancies. A novel CD19-targeting ADC presents strong preclinical anti-lymphoma activity.
#1073Increased internalization and processing of the CD37-targeting antibody-drug conjugate, naratuximab emtansine (IMGN529), in the presence of rituximab leads to enhanced potency in diffuse large B-cell lymphoma modelsHicks SW, Lai KC, Yi Y, Shah P, Gavrilescu CL, Ponte J, Sloss CM, Romanelli A.April 3, 2017, 8:00-12:00 PM | Section 1Data show enhanced activity of rituximab plus IMGN529 combination in DLBCL models, supporting the clinical development of this combination.