Advancing Bispecific Antibodies and Combination Therapy to the Clinic

- 推動雙特異性抗體和並用療法進入臨床 -


The development of bispecific antibodies is one of the hottest areas in biologic research at the moment and their advancement to preclinical and clinical development will determine what the future of this area will look like. The 8th Annual Advancing Bispecific Antibodies and Combination Therapy to the Clinic conference brings together leading researchers in this area to strategize on the safety and efficacy of new constructs, review the latest clinical results, and talk about expanding their use beyond oncology.

Final Agenda

Scientific Advisory Board

Frank Comer, PhD, Senior Scientist, AstraZeneca
Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen, Conference Chairman

5月5日(二)

Recommended Short Course*

SC11: Developability of Bispecific Antibodies: Assays and Case Studies

*Separate registration required.

5月6日(三)

7:15 am Registration and Morning Coffee

7:25 Women in Science Panel Discussion with Continental Breakfast

Moderator:
Rochard_LucieLucie Rochard, PhD, Liaison, Scientific & Entrepreneurial Initiatives; Director, Innovation Services, Massachusetts Biotechnology Council


Panelists:
Nora MinevaNora Mineva, PhD, CSO, Adecto Pharmaceuticals


Liu_TinaTina Liu, MBA, Co-Founder and CEO, Ally Therapeutics


Chadwich_JenniferJennifer Chadwich, PhD, Vice President, Biologic Development, BioAnalytix, Inc.


INNOVATION IN IMMUNO-ONCOLOGY BISPECIFIC ANTIBODIES

8:40 Current Status of Bispecifics Biologics and Combination Biologics Therapies

Dixit_RakeshRakesh Dixit, PhD, DABT, President & CEO, Bionavigen

In this talk, we will discuss next-generation bispecifics biologics, including IgG antibody, BiTE, CAR-T cells, CD-3 T cells and enhanced TCR-based bispecifics. We’ll continue into the clinical landscape of bispecifics and learnings from the successful and failed bispecifics, as well as combinations biologics, and whether we should consider them friends or foes.

9:20 Ultraspecific Antibodies for Truly Specific Targeting of Solid Tumors

Finlay_JonnyJonny Finlay, PhD, CEO, UltraHuman Ltd.

The effective treatment of solid tumors with antibody-based drugs typically relies on extremely potent mechanisms of action. Tumor targets are rarely, if ever, solely expressed in the tumor and antibody selectivity to the tumor-expressed target is often poor. This presentation will outline UltraHuman’s efforts to reliably overcome these limitations and improve response rates in solid tumor therapy.

9:50 REGN4018 Is a Mucin 16 Bispecific T Cell-Engaging Antibody for the Treatment of Ovarian Cancer

Crawford_AlisonAlison Crawford, PhD, Senior Staff Scientist, Oncology & Angiogenesis, Regeneron Pharmaceuticals

REGN4018 binds both MUC16 and CD3. REGN4018 inhibited growth of human tumors in a xenogenic model and murine tumors expressing human MUC16. Combination with an anti-PD-1 antibody enhanced this efficacy. Immuno-PET imaging demonstrated localization of REGN4018 in MUC16-expressing tumors as well as in T cell-rich organs. Toxicology studies in cynomolgus monkeys showed minimal and transient increases in serum cytokines and C-reactive protein following REGN4018 administration with no overt toxicity.

10:20 Coffee Break in the Exhibit Hall with Poster Viewing

10:30 Women in Science Speed Networking in the Exhibit Hall

11:05 Combinatorial Immune Checkpoint Blockade Using Clinical Stage Bispecific DART® Molecules MGD013 and MGD019

Berezhnoy_AlexeyAlexey Berezhnoy, PhD, Scientist III, Cell Biology and Immunology, MacroGenics, Inc.

This talk will dive into an investigation of co-expression of multiple immune checkpoint receptors by tumor-infiltrating lymphocytes, whose co-blockade provides additional benefits in immunotherapy. We will also discuss selection and format optimization of bispecific molecules for simultaneous blockade of two checkpoint pathways, in addition to discussing MGD013 and MGD019 preclinical pharmacology, IND enabling studies and clinical trial design.

11:35 Tumor Targeted 4-1BB Activation with PRS-343, a HER2/4-1BB Antibody-Anticalin Bispecific

Bruns_IngmarIngmar Bruns, MD, PhD, Senior Vice President, Head of Clinical Development, Pieris Pharmaceuticals GmbH

In this talk we will share comprehensive clinical experience gained from interim analyses of the PRS-343 trials and provide an overview about the broader Pieris pipeline of 4-1BB targeting antibody-anticalin bispecific molecules.


12:05 pm Optimization of Preclinical Safety and Efficacy of Anti-HER2/CD3 TDB

Junttila_TeemuTeemu Junttila, PhD, Principal Scientist, Translational Oncology, Genentech

Systemic cytokine release and on-target/off-tumor toxicity on normal tissues are the main adverse effects limiting the applicability of T cell redirecting bispecific antibodies. We have investigated how affinity to HER2 and CD3 impacts anti-tumor efficacy, distribution and preclinical safety of anti-HER2/CD3 TDB and describe how that affinity has a major impact on tolerability. We further demonstrate that cytokine release and adverse effects can be effectively mitigated by a simple dose-fractionation or prophylactic cytokine blockade. Our studies support detailed preclinical optimization of therapeutic candidates in relevant safety and efficacy models and suggest that fine tuning the affinities to both the antigen and CD3 is likely critical to maximize therapeutic index in clinical use.

12:35 Sponsored Presentation (Opportunity Available)

1:05 Session Break

1:10 Luncheon Presentation I to be Announced

1:40 Luncheon Presentation II (Sponsorship Opportunity Available)

2:10 Session Break

2:30 Development of CDX-527, a Novel Bispecific-Immune Modulating Antibody Targeting PD-L1 and CD27

Goldstein_JoelJoel Goldstein, PhD, Senior Director, R&D, Celldex Therapeutics

The success of antibodies that block the PD-1 signaling pathway has led to a tremendous effort in combinations and bispecifics to further improve outcomes in cancer. CD27 is a costimulatory molecule that provides a complementary target to the PD-1/PD-L1 axis on T cells. A tetravalent format was selected for CDX-527 that along with potent PD-1 blockade provides efficient cross-linking, which is important for CD27 agonistic activity, by allowing interaction with both Fc-receptor and PD-L1 bearing cells.

3:00 Blockade of Glycol-Immune Checkpoints (Siglecs) Using Bifunctional EAGLE for Cancer Immunotherapy

Peng_LiLi Peng, PhD, Senior Vice President, Research and Early Product Development, Palleon Pharmaceuticals

The Siglec/sialoglycan axis has recently emerged as a new mechanism of cancer immune evasion. We engineered a human sialidase and developed a bifunctional antibody-sialidase platform named EAGLE to inhibit this axis. EAGLE showed enzyme-dependent robust monotherapy efficacy with complete regressions and immune memory in preclinical tumor models. We further demonstrated EAGLE’s mechanism of modulating innate and adaptive antitumor responses and identified correlative pharmacodynamic biomarkers to EAGLE treatment in preclinical models.

3:30 Sponsored Presentation (Opportunity Available)

4:00 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Problem-Solving Breakout Discussions - View All Breakout Discussion Topics

TABLE: Pre-Clinical Mouse Models to Examine Immunotherapeutics

Moderator: Alison Crawford, PhD, Senior Staff Scientist, Oncology & Angiogenesis, Regeneron Pharmaceuticals

  • Xenogenic versus syngeneic models
  • Read-outs examining T cell activation
  • Combination therapy in pre-clinical models

TABLE: Pros and Cons of Assays to Predict the Half-Life of Antibodies in Primates

Moderator: Gundo Diedrich, PhD, Director, Antibody Engineering, MacroGenics, Inc.

  • FcRn affinity chromatography
  • Cell-based assays with FcRn-expressing cell lines (transcytosis assays, recycling assays)
  • In vitro plasma stability assays

6:00 Taste of New England Networking Reception in the Exhibit Hall with Poster Viewing

7:15 End of Day

5月7日(四)

8:00 am Registration and Morning Coffee

NOVEL MODALITIES AND NOVEL BIOLOGY: MAXIMIZING THE POTENTIAL OF BISPECIFIC TARGETING

8:30 Chairperson’s Remarks

Frank Comer, PhD, Senior Scientist, AstraZeneca


8:35 KEYNOTE PRESENTATION: Bispecific Antibody Drug Development

Parren_PaulPaul Parren, PhD, Executive Vice President, Head, R&D, Lava Therapeutics B.V.

Landmark advances in the engineering and development of bsAbs are enabling unprecedented versatility in therapeutic antibody concepts. Currently more than 20 different commercialized technology platforms are available for bsAb creation and development, two bsAbs are marketed and over 85 are in clinical development. A defining bsAb feature is their potential for novel functionalities – that is, activities that do not exist in mixtures of the parental or reference antibodies. This presentation will provide insights in the design and function of these so-called obligate bsAb and their potential in drug development.

9:05 Oncolytic Adenoviruses Armed with BiTEs and BiKEs

Alemany_RamonRamon Alemany, PhD, Scientist, ProCure and Oncobell Programs, Catalan Institute of Oncology - IDIBELL

Oncolytic viruses replicate and induce lymphocyte infiltration in tumors. However, the infiltrating T cells target exclusively virus-infected cells due to the immunodominance of viral antigens. BiTEs and BiKEs secreted from the oncolytic virus offer a unique opportunity to retarget T cells or NKs towards non-infected bystander tumor or stromal cells. Further, selective expression in tumors reduces the potential systemic toxicity of these engagers. Results on this strategy will be presented.

Applied-Biomath 9:35 Presentation to be Announced

10:05 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Award

11:05 T Cells Redirected with Modular Biepitopic and Bispecific Antibody Mimic Receptors

Liu_RiheRihe Liu, PhD, Associate Professor, Chemical Biology and Medicinal Chemistry, Eschelman School of Pharmacy, University of North Carolina, Chapel Hill

One of the effective approaches to improving the outcome of CAR T cell therapies is by targeting multiple tumor-associated antigens (TAA). To address current drawbacks in achieving multiple-tumor targeting using scFvs, we used single-domain antibody mimics with small size, simple structure, and high stability that can be modularly engineered on the surface of immune cells to acquire multifunctional TAA recognition. We demonstrated that protein domains targeting EGFR and HER2 of the ErbB family can be assembled into antibody mimic receptor (amR) molecules, and efficiently redirect T cells for biepitopic or bispecific TAA recognition in vitro and in vivo.

11:35 Selective Blockade of the Immune Checkpoint CD47 Using Bi- and Multi-Specific Antibodies

Fischer_NicolasNicolas Fischer, PhD, CEO, Light Chain Bioscience, Novimmune SA

Safe and selective blockade of the innate immune checkpoint CD47 can be achieved using bispecific antibodies (bsAb) having two arms with different affinities. This dual targeting concept has been validated in different preclinical models of human cancer and is now being explored in patients with a bsAb generated using our kappa-lambda body platform.

12:05 pm A Comprehensive Immunotherapy Strategy for Solid Cancers

Tushir-Singh_JogenderJogender Tushir-Singh, PhD, Assistant Professor, Biochemistry & Molecular Genetics, UVA Cancer Center, University of Virginia School of Medicine

Farletuzumab, an ADCC activating humanized antibody targeted against folate receptor alpha-1 (FOLR1), improves survival advantage for a very small subset of ovarian cancer patients having low cancer antigen-125 levels. Since a larger ovarian cancer population highly overexpresses cancer antigen-125, we argue that ADCC-based approaches are not clinically feasible options. Therefore to achieve a clinically applicable and patient centered approach, we hypothesize enhancing farletuzumab’s anti-tumor activity beyond and independent of the ADCC function. One such approach is epithelial cancer enriched death receptor 5 (DR5/TRAIL-R2) activating antibodies. TRAIL-R2 is a major extrinsic apoptotic pathway receptor expressed in tumors of epithelial origin and we have engineered, tested and characterized a novel bispecific-anchored Cytotoxicity-activator (BaCa) antibody that combines the specificities against the FOLR1 and TRAIL-R2. In our preliminary studies, the BaCa antibody not only generates an exceedingly oligomerized and activated TRAIL-R2 receptor complex, but also induces a very high level of apoptosis that is remarkably selective to ovarian cancer cells and tumors. Importantly, the cytotoxic function of the BaCa antibody is self-sufficient and does not require selective infiltration and ADCC activity of immune effector NK cells or cytotoxic signaling of T cells into the tumors. Our studies strongly support the high in vivo activity of BaCa antibody in tumor xenografts as well as in patient derived cell lines compared to clinically failed antibodies. Since extrinsic TRAIL-R2 induced cell-death is independent of intrinsic p53-mediated apoptosis, our data also support a tailored treatment strategy for the majority of serous ovarian carcinomas (>90%) harboring p53 loss-of-function mutations. In summary, the described BaCa antibody strategy represents a “moonshot strategy” to generate effective therapy for advanced stage serous adenocarcinoma patients without the intervention of immune effector cells. If successful, this approach will significantly improve the survival of ovarian cancer patients with desirable clinical safety.

12:35 End of Advancing Bispecific Antibodies and Combination Therapy to the Clinic


Recommended Short Course*

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*Separate registration required.

* 活動內容有可能不事先告知作更動及調整。

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