On May 15, 2020 Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) constructs, reported that it will present at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, occurring June 22 – 24, 2020 (Press release, Exicure, MAY 15, 2020, View Source [SID1234558163]).

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

Data to be presented include:

Gene expression analysis from biopsied tumors, showing trends to increased lymphocytes in the injected tumor after intratumoral (IT) AST-008 and in both injected and un-injected tumors after IT AST-008 plus pembrolizumab combination therapy
Dose dependent activation of key immune cells and immune system signal proteins (cytokines/chemokines) after IT AST-008 treatment and AST-008 plus pembrolizumab treatment
An emerging safety profile consisting of mostly injection site reactions and flu-like symptoms, likely reflecting local and systemic immune activation
No AST-008-related serious adverse events or dose limiting toxicity have been reported
This poster will be 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 starting on June 22nd.

On May 15, 2020 Samsung Bioepis Co., Ltd. reported that four-year follow-up results of the Phase 3 study for ONTRUZANT, a biosimilar of the reference medicine HERCEPTIN1 (trastuzumab), will be presented at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program organized by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), which will be held from May 29-31, 2020 (Press release, Samsung Bioepis, MAY 15, 2020, View Source [SID1234558162]).

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The four-year follow-up data is part of the ongoing follow-up study to assess cardiac safety and survival outcome in a subgroup of patients from the Phase 3 study who completed neoadjuvant and adjuvant therapy for one year. Among 875 patients from the Phase 3 study, a total of 367 patients were enrolled in the extension study, with a median follow-up of 53 months. During the follow-up period, cardiac safety was comparable between ONTRUZANT (SB3) and reference trastuzumab (TRZ), with no occurrence of symptomatic congestive heart failure (CHF) and a very low incidence of asymptomatic significant left ventricular ejection fraction (LVEF) decrease (SB3, n=1; TRZ, n=2). Four-year event-free survival (EFS) rates and overall survival (OS) rates were also comparable between ONTRUZANT and reference trastuzumab (EFS: SB3 83.4% vs. TRZ 80.7%; OS: SB3 94.4% vs. TRZ 89.6%).

"The four-year follow-up results further support comparable safety and efficacy profiles of ONTRUZANT to reference trastuzumab," said Seongwon Han, Vice President, Medical & Lifecycle Safety Lead, Samsung Bioepis. He continued, "We hope these findings on long-term safety and efficacy help build confidence in the use of biosimilars for prescribers and patients."

The poster of this study will be presented at the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program, as follows:

[578] Four-year Follow-up of a Phase III Study Comparing SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in HER2-positive Early or Locally Advanced Breast Cancer in Neoadjuvant Setting ‒ Poster session (Poster 70) * Poster sessions will be available on demand beginning Friday, May 29, 2020 at 8:00 a.m. ET
About SB3 (ONTRUZANT) Follow-up Study (SB3-G31-BC-E)
Among 875 patients who participated in the Phase 3 study of SB3, a total of 367 patients (SB3, n=186; TRZ, n=181) were enrolled in a five-year follow-up study. The aim of this follow-up study was to observe the incidence of symptomatic congestive heart failure (CHF), asymptomatic significant left ventricular ejection fraction (LVEF) decrease, incidence of other cardiac events, event-free survival (EFS), and overall survival (OS). The median follow-up duration from initiation of the Phase 3 study was 53 months.
During the follow-up period, incidence of asymptomatic significant LVEF decrease was comparable between SB3 and reference trastuzumab (SB3, n=1; TRZ, n=2), with all patients recovering with LVEF who reported 50% or above. No symptomatic CHF, cardiac death, or other significant cardiac condition occurred in either group during the follow-up period.
Four-year EFS rates were 83.4% for SB3 and 80.7% for reference trastuzumab (HR 0.77, 95% CI 0.47-1.27), while four-year OS rates were 94.4% for SB3 and 89.6% for reference trastuzumab (HR 0.53, 95% CI 0.24-1.16).
Within the group of patients who received reference trastuzumab, the patients exposed to at least one vial from the reference trastuzumab lots with expiry dates from August 2018 to December 2019 during neoadjuvant period showing lower (drifted) levels of antibody dependent cellular cytotoxicity (ADCC) were classified as the "drifted TRZ group," and the remaining patients who were not exposed to any vials from the reference trastuzumab lots with lower levels of ADCC were classified as the "non-drifted TRZ group." In an ad-hoc analysis, there was no difference observed in EFS (HR 1.60, 95% CI, 0.58-4.40, p=0.362) and OS (HR 0.97 95% CI, 0.11-8.50, p=0.975) between SB3 and non-drifted TRZ group. There was a difference observed in EFS (HR 5.50 95% CI, 1.81-16.65, p=0.003) and OS (HR 15.35 95% CI, 1.78-132.69, p=0.013) between drifted TRZ and non-drifted TRZ group.

About ONTRUZANT (trastuzumab-dttb)
ONTRUZANT is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer:

As part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel
As part of a treatment regimen with docetaxel and carboplatin
As a single agent following multi-modality anthracycline-based therapy
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product
* High-risk is defined as ER/PR positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.

ONTRUZANT is indicated:

In combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer
As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product

ONTRUZANT is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.

Select Important Safety Information

Cardiomyopathy

Administration of ONTRUZANT can result in sub-clinical and clinical cardiac failure
Evaluate left ventricular function in all patients prior to and during treatment with ONTRUZANT. Discontinue ONTRUZANT treatment in patients receiving adjuvant therapy and withhold ONTRUZANT in patients with metastatic disease for clinically significant decrease in left ventricular function
Infusion Reactions; Pulmonary Toxicity

Administration of ONTRUZANT can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of administration. Interrupt ONTRUZANT infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue ONTRUZANT for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome
Embryo-Fetal Toxicity

Exposure to ONTRUZANT during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception
Exacerbation of Chemotherapy-Induced Neutropenia

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab products in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not
Most Common Adverse Reactions

The most common adverse reactions for trastuzumab products in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia
The most common adverse reactions for trastuzumab products in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia
These are not all of the risks associated with ONTRUZANT. For additional information on ONTRUZANT indications, as well as Important Safety Information related to its use, including Boxed WARNINGS, please see the ONTRUZANT Prescribing Information HERE.

On May 15, 2020 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, and BioInvent International AB ("BioInvent") (OMXS: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported new highly promising preclinical data demonstrating the broad therapeutic potential of BT-001, an anti-CTLA4 antibody-encoding oncolytic virus, against solid tumors (Press release, Transgene, MAY 15, 2020, View Source [SID1234558160]). These data will be presented at the AACR (Free AACR Whitepaper) 2020 Virtual Annual Meeting II.

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BT-001 is a multifunctional oncolytic virus being co-developed by Transgene and BioInvent. It has been engineered to encode a Treg-depleting, anti-CTLA4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and GM-CSF. It uses Transgene’s Vaccinia-based Invir.IO viral vector platform to deliver this powerful immunotherapy directly into the tumor.

Key results:

The new data demonstrate a powerful therapeutic effect, indicated by curative potential as a single agent in multiple syngeneic mouse models spanning solid tumor models (CT26, EMT6, C38, and A20).
An improved therapeutic window relative to systemic anti-CTLA4 blockade was indicated by higher, receptor-saturating, anti-CTLA4 antibody intratumoral concentrations versus much lower levels in the blood compartments.
BT-001’s activity was further enhanced when combined with anti-PD-1 antibody therapy – opening up the potential for powerful dual checkpoint blockade treatment regimens.
These promising findings will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, taking place June 22-24. The abstract is posted online today.

The oncolytic virus, the anti-CTLA4 and the GM-CSF therapeutic strategies that underpin BT-001 have already demonstrated activity in humans based on their ability to induce a fundamental change in the tumor microenvironment and anti-tumor activity.

Looking at the clinical landscape, BioInvent and Transgene are confident that BT-001 could either be used as a monotherapy or be associated with standard of care immunotherapy options such as anti-PD1/anti-PD-L1 therapies in order to deliver improved clinical outcomes for patients with solid tumors.

Éric Quéméneur, Pharm.D., Ph.D., Executive VP, Chief Scientific Officer of Transgene, added: "The preclinical results generated with BT-001 have been remarkable and we remain extremely confident in its ability to change the treatment landscape for a significant number of solid tumors. We have submitted our first clinical trial application for BT-001 in March 2020 and are working hard to make sure we can take our first multifunctional Invir.IO oncolytic into the clinic before the end of 2020, despite uncertainties caused by the Covid-19 pandemic."

Martin Welschof, CEO of BioInvent, says: "We are very pleased with these data on BT-001, which indicate the oncolytic virus has the potential to treat a broad range of cancers. This is a further demonstration of the power of BioInvent’s technology platform, multiplied by our strong cooperation with Transgene, and we look forward to further investigating the capabilities of this promising therapeutic option."

Title of the poster: "BT-001, an oncolytic Vaccinia virus armed with a Treg-depletion-optimized recombinant human anti-CTLA4 antibody and GM-CSF to target the tumor microenvironment."
Authors: Jean-Baptiste Marchand, Monika Semmrich, Laetitia Fend, Matilda Rehn, Nathalie Silvestre, Ingrid Teige, Johann Foloppe, Linda Mårtensson, Eric Quéméneur, Björn Frendeus
Abstract Number: 2902
Session Date: June 22-24, 2020
Poster Session Title: Inflammation, Immunity, and Cancer / Modifiers of the Tumor Microenvironment 2
Poster number: 5602
The abstract can be downloaded on the AACR (Free AACR Whitepaper) website.

On May 15, 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, MAY 15, 2020, View Source [SID1234558159]). The data will be shared via poster presentation at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting II being held June 22-24, 2020.

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"To address the unmet needs of additional patient populations, we sought to develop a FRα-targeting ADC active against ovarian cancer and other tumor types with a broad range of FRα expression. IMGN151 demonstrates our continued innovation in the field of ADCs, incorporating several key design elements including a novel biparatopic antibody that enhances binding with FRα and payload delivery as well as DM21, our most advanced maytansinoid derivative that, together with a peptide linker, provides improved stability and increased bystander anti-tumor activity," said Eric Westin, MD, Vice President, Clinical Development and Translational Sciences for ImmunoGen. "In preclinical models, IMGN151 showed activity not only in high FRα-expressing tumors, but also improved activity in medium and low FRα-expressing tumors, suggesting promising potential in a broad set of patients with an array of tumor types. As we continue to analyze these data, we look forward to advancing IMGN151 into preclinical development."

PRECLINICAL DATA ON IMGN151
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.

Key findings include:

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.
In tumor cells with medium and high FRα expression, IMGN151 boosted antibody binding events and payload delivery by 100% and 170%, respectively.
IMGN151 increased ADC half-life by 60 hours and conjugate exposure in vivo by 40%, as compared to IMGN853.
In vitro, IMGN151 was up to 200 times more active against four FRα-medium cell lines. IMGN151 also had better bystander killing activity in a mixed culture of target-positive and negative cells.
In vivo, IMGN151 induced complete tumor regressions of human tumor xenograft models with high, medium, and low FRα expression. All tested doses were well tolerated.
POSTER PRESENTATION

Title: "IMGN151: A Next Generation Folate Receptor Alpha Targeting Antibody Drug Conjugate Active Against Tumors with Low, Medium, and High Receptor Expression"
Day/Time: Monday, June 22, 2020 at 9:00 AM ET
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
Abstract: 2890
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.

On May 15, 2020 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, reported it will present new preclinical data on three XmAb 2+1 bispecific antibody programs and an IL-12-Fc cytokine program at the second session of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting, being held June 22-24, 2020 (Press release, Xencor, MAY 15, 2020, View Source [SID1234558158]). Abstracts for these poster presentations are now available on AACR (Free AACR Whitepaper)’s website.

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"Xencor has expanded our T-cell redirecting CD3 class of bispecific antibodies with a mixed valency format that uses the same heterodimeric Fc domain as our other bispecific antibodies and cytokines, but with two identical tumor targeting domains and one CD3 targeting domain—the XmAb 2+1 bispecific antibody. These two tumor-targeting binding domains can bind together when there’s more target present, a property called avidity," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. "Our 2+1 format, along with avidity tuning, enables higher selectivity for tumor antigen-expressing cells and greater flexibility in tuning the potency and potentially the efficacy and tolerability of the molecule, as well as the ability to address an expanded set of tumor antigens."

"At AACR (Free AACR Whitepaper), we are presenting data from preclinical models showing strong, selective tumor killing from XmAb 2+1 bispecific antibody programs that target PSMA, mesothelin and ENPP3, the last of which is an underexplored tumor antigen overexpressed on renal cell carcinomas. In addition, we are introducing our next cytokine program in oncology, a potency-reduced IL-12 Fc fusion, which demonstrates strong-anti-tumor activity in preclinical models, as a single agent and in combination with an anti-PD1 antibody," said Dr. Desjarlais.

Poster Presentation Details

Abstract: 2286
Title: XmAb30819, an XmAb 2+1 ENPP3 x CD3 bispecific antibody for RCC, demonstrates safety and efficacy in in-vivo preclinical studies
Session: Therapeutic Antibodies 1
Abstract: 5663
Title: Affinity tuned XmAb 2+1 PSMA x CD3 bispecific antibodies demonstrate selective activity in prostate cancer models
Session: Therapeutic Antibodies 4
Abstract: 5654
Title: Affinity tuned XmAb 2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell directed cell cytotoxicity of human ovarian cancer cells
Session: Therapeutic Antibodies 4
Abstract: 5549
Title: Potency-reduced IL-12 heterodimeric Fc-fusions exhibit strong anti-tumor activity
Session: Immunomodulatory Agents and Interventions 2
These posters and audio descriptions will be available to registrants of the AACR (Free AACR Whitepaper) Virtual Annual Meeting at 9:00 a.m. EDT on Monday, June 22. Posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.