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CANCER BIOTHERAPEUTICS

ADCs, Multi-Specifics, Combined Therapies and Immunotherapy

Inaugural

TUESDAY , 5 NOVE MBER

»»PRE-CONFERENCE PLENARY SESION

16:55 Designing Receptor Binding Proteins with Highly Potent

Biological Function

Andreas Plückthun, Ph.D., Director and Professor, Biochemistry, University

of Zurich

Non-IgG molecules, unless armed with toxins or other effector units, are

usually thought to be limited in the biological responses they can elicit.

However, Designed Ankyrin Repeat Proteins (DARPins) are particularly

versatile, because of their favorable biophysical properties, and they can be

engineered into many formats. Using DARPins generated against members

of the EGFR family, and a combination of x-ray crystallography, signaling

studies, and in vivo experiments, it will be demonstrated how molecules

could be engineered to selectively induce apoptosis in tumors, and their

mechanism of action has been deduced. New intracellular sensors will be

described for such studies.

17:45 Immunotherapy with BiTE® Antibodies

Luis Borges, Ph.D., Scientific Director, Therapeutic Innovation Unit, Amgen, Inc.

BiTE® antibodies are potent bispecific single-chain antibodies that redirect T

cells to kill tumors. They engage a tumor target and a constant region of the

T cell receptor to recruit and activate polyclonal T cells to eliminate tumors.

They have demonstrated potent efficacy in various preclinical tumor models

and have now transitioned to clinical studies. Blinatumomab, a CD19xCD3

BiTE® antibody, is in clinical development and has shown high single-agent

response rates in patients with refractory or relapsed B-ALL and B-NHL.

18:30 End of Day

Wednesday, 6 November

07:45 Registration and Morning Coffee

08:30 Chairperson’s Opening Remarks

Jason Baum, Ph.D., Principal Scientist, Research, Merrimack Pharmaceuticals, Inc.

MULTI-SPECIFIC ANTIBODY PRODUCTS

08:35 Two-in-One Antibody Targeting EGFR and HER3 and Platform

Update

Germaine Fuh, Ph.D., Senior Scientist, Antibody Engineering, Genentech, Inc.

Mutation at the antigen binding sites of a mono-specific antibody may recruit a

second binding specificity such that each Fab arm exhibits dual binding function and

IgG with this dual action Fab (DAF) can be produced as conventional IgG. Proofof-

concept is a HER2/VEGF Two-in-One antibody; EGFR/HER3 Two-in-One DAF

antibody is in clinical phase II trial for treating epithelial cancer. The talk will cover the

generation and development of the EGFR/HER3 DAF antibody including preclinical

and clinical phase I data.

09:05 MM-141, a Bispecific Antibody Co-Targeting IGF-1R and Erbb3,

Overcomes Network Adaptation by Blocking Redundant Survival

Pathways

Jason Baum, Ph.D., Principal Scientist, Research, Merrimack Pharmaceuticals, Inc.

An integrated Network Biology approach was used to design and optimize MM-

141 to overcome limitations of first generation IGF-1R therapies by also blocking

heregulin-mediated compensation through ErbB3. MM-141 potentiates the activity

of both targeted therapies and chemotherapies through the combined inhibition

of PI3K/Akt/mTOR signaling as well as control over feedback loops triggered by

these agents.

09:35 Bispecific κλ-bodies for Selective Inhibition of CD47 in Cancer Cells

Nicolas Fischer, Ph.D., Head, Research, Novimmune SA

We have used our κλ-body platform to generate CD47-neutralizing bispecific

antibodies. These fully human antibodies are composed of a CD47-specific arm

and a targeting arm, specific to a tumor associated antigen (TAA). The preferential

neutralization of CD47 on TAA-expressing cancer cells should therefore show better

pharmacological properties and a broader therapeutic window as compared to nontargeted

anti-CD47 monoclonal antibodies. The presentation will also highlight how

light chain diversity can be exploited to create bispecific antibodies with favorable

manufacturability and stability profiles that facilitate their development path.

10:05 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

11:05 Targeting Tumor Microenvironmental Signals with Bispecific

Antibodies

Alessandro Angelini, Ph.D., David H. Koch Institute for Integrative Cancer Research,

Massachusetts Institute of Technology (MIT)

We have developed bispecific antibodies that locally contravene soluble signaling

factors that establish the supporting tumor microenvironment that enables tumor

survival and growth. Soluble factors such as VEGF, TGF-β, and IL-8 play a demonstrated

role in tumorigenesis, and enhanced interdiction of these signals within the tumor

should enhance the therapeutic index of cancer therapy.

11:35 Novel Multi-Targeting Antibody Mixtures: Mode of Action and

Advantages Over Other Approaches

Michael Kragh, Ph.D., Director, Antibody Pharmacology, Symphogen A/S

This talk will present the selection of antibodies against tumor-related antigens to

obtain synergistic combinations, the benefits of simultaneous targeting of multiple

receptors, and examine pan-HER (EGFR, HER2 and HER3) targeting to address

tumor heterogeneity and plasticity.

12:05 Sponsored Presentation (Opportunity Available)

12:35 Luncheon Presentations (Sponsorship Opportunities Available) or

Lunch on Your Own

ADVANCES WITH CANCER IMMUNOTHERAPY

14:00 Chairperson’s Remarks

Andrea van Elsas, CSO, BioNovion B.V.

14:05 Cancer Immunotherapy Using Immune Modulating Antibodies

Andrea van Elsas, CSO, BioNovion B.V.

Immune rejection of human cancer has been an elusive goal until recently. T cell

modulating antibodies targeting CTLA-4 and the PD-1 pathway induced clinically

meaningful responses and long-term benefit in patients with metastatic cancer.

Successful immune rejection can come with significant immune related adverse

events. Immune oncology agents do not directly tumor cells but treat the patient’s

immune cells. In this presentation, the discovery of immune modulating antibodies

and their translation into clinical success will be discussed.

14:35 Immunocytokines: A Novel Potent Class of Armed Antibody

Laura Gualandi, Ph.D., Philochem A.G.

Antibodies are effective tools that can deliver molecules with potent therapeutic

activity, such as Cytokines, to the tumor site, minimizing toxic effects. Aspects like

molecular format, valence and the chosen target antigen contribute to the efficacy of

the immunocytokines in vivo. Combinatory therapeutic strategies with other agents

have also been recently investigated. This talk will cover advanced preclinical and

clinical data on armed antibodies discovered and developed by the Philogen group.

15:05 NKTT320: A Humanized Monoclonal Antibody for Cancer

Immunotherapy

Robert Mashal, CEO, NKT Therapeutics

Activation of iNKT cells has been shown to have therapeutic effects both in

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6-7 November 2013

preclinical models and in patients with cancer, and represents an important pathway

for the immunotherapy of cancer. iNKT cells have an invariant T cell receptor (iTCR).

NKT Therapeutics is developing NKTT320, a humanized monoclonal antibody which

specifically recognizes the iTCR present exclusively on iNKT cells, and has been

shown to activate iNKT cells both in vitro and in vivo.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

16:15 Novel Tumor-Targeted, Engineered IL-2 Variant (IL-2v)-Based

Immunocytokines for Immunotherapy of Cancer

Ekkehard Moessner, Ph.D., Group Leader, Protein Engineering, pRED, Roche Glycart A.G.

A novel class of immunocytokines will be discussed that are based on Fc containing

and also on non-Fc containing building blocks. The IL2 component is optimized for

improved performance in tumor targeting. Enhancement of in vivo efficacy, when

combined with ADCC competent antibodies, will be discussed.

ANTIBODY-DRUG CONJUGATES AND PAYLOADS

16:45 Next-Generation ADCs: Enabling Higher Drug Loading,

Alternative Payloads, and Alternative Targeting Moieties

Timothy B. Lowinger, Ph.D., CSO, Mersana Therapeutics, Inc.

The application of polymers to antibody-drug conjugate (ADC) design can provide

numerous advantages, including significantly higher capacity for drug payload;

utilization of alternative payloads not suitable for direct conjugation; improvement of

physicochemical properties; and utilization of protein recognition scaffolds beyond

the commonly used IgGs. Examples of these benefits achieved using Mersana’s

polyacetal-based conjugation system to create next-generation ADCs

will be presented.

17:15 Problem Solving Roundtable Discussions

Table 1: Engineering of Bispecific Antibodies

Moderator: Nicolas Fischer, Ph.D., Head, Research, Novimmune SA

Table 2: Antibody-Drug Conjugates: Linkers and Payloads

Moderators: Robert Lutz, Ph.D., Vice President, Translational Research &

Development, ImmunoGen, Inc.

Timothy B. Lowinger, Ph.D., CSO, Mersana Therapeutics, Inc.

Table 3: Site-Specific Conjugation of ADCs

Moderator: Pavel Strop, Ph.D., Associate Research Fellow, Protein

Engineering, Rinat-Pfizer, Inc.

Table 4: Cancer Immunotherapy: Reaping the Benefits

Moderators: Andrea van Elsas, CSO, BioNovion B.V

Luis Borges, Ph.D., Scientific Director, Amgen, Inc.

Table 5: Cancer Biotherapeutics in the Clinic

Moderators: Jason Baum, Ph.D., Principal Scientist, Research, Merrimack

Pharmaceuticals, Inc.

Martine Piccart, M.D., Ph.D., Head, Medical Oncology, Jules Bordet

Institute; Chair, ESMO (European Society for Medical Oncology)

18:15 Networking Reception in the Exhibit Hall with Poster Viewing

19:15 End of Day One

Thursday, 7 November

07:45 Breakfast Presentation (Sponsorship Opportunity Available) or

Morning Coffee

08:30 Chairperson’s Remarks

Robert Lutz, Ph.D., Vice President, Translational Research & Development,

ImmunoGen, Inc.

08:35 A Universal Chemically Driven Approach for Constructing

Homogeneous ADCs

David Jackson, Ph.D., Principle Scientist, ADC Discovery, Igenica, Inc.

Current ADCs in clinical development are heterogeneous mixtures that differ in

both DAR (drugs/antibody) and their conjugation sites. Igenica has invented novel

site-specific linkers to enable the synthesis of homogeneous ADCs. The linkers

are compatible with a variety of drug payloads and can be applied to any antibody.

Homogeneous ADCs were synthesized using the novel linkers and compared to

heterogeneous ADCs made with conventional linkers. Analytical data and activity of

the ADCs in tumor models will be presented.

09:05 Location Matters: Site of Conjugation Modulates Stability and

Pharmacokinetics of Antibody-Drug Conjugates

Pavel Strop, Ph.D., Associate Research Fellow, Protein Engineering, Rinat- Pfizer, Inc.

To understand the role of conjugation site, we developed an enzymatic method for

site-specific antibody-drug conjugation. This allowed us to attach diverse compounds

at multiple positions and investigate how the site influences stability, toxicity, and

efficacy. We show that the conjugation site has significant impact on ADC stability

and pharmacokinetics in a species-dependent manner. With this method, it is

possible to produce homogeneous ADCs and tune their properties to maximize the

therapeutic window.

09:35 Development of Second Generation Duocarmycin ADCs with

Superior Therapeutic Window

Marion Blomenröhr, Ph.D., Program Manager Biopharmaceuticals, Synthon

Biopharmaceuticals

The first generation ADCs have successfully exploited the mAb-driven tumor cell

targeting for optimization of efficacy, but have failed to reduce off-target toxicities.

This presentation will highlight Synthon’s second generation Linker-Drug technology

and its complementarity with novel proprietary duocarmycin payloads yielding highly

stable and potent ADCs, with an improved in vivo therapeutic window.

10:05 Producing Better Antibody-Drug Conjugates Sponsored by

(ADCs) Using ThioBridge™ Conjugation

Antony Godwin, Ph.D., Director, Science & Technology, PolyTherics Ltd

Next-generation antibody-drug conjugates will be required to be less heterogeneous

and have better stability. PolyTherics has developed ThioBridge™ for improved

conjugation of a cytotoxic payload at the disulfides bonds of antibodies, antibody

fragments and other targeting proteins. With ThioBridge™, the resulting ADC

has the benefit of reduced heterogeneity, as the drug to antibody ratio is limited

to a maximum of 4 with little DAR 0 species. Stability is also enhanced, as unlike

single thiol conjugation approaches at disulfides, ThioBridge™ is not prone to

drug deconjugation reactions in serum. In vitro and in vivo data for mAb and Fab

conjugates with an established payload confirms specific binding and activity.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

»»PLENARY SESION

11:05 Medical Treatment of HER2 Positive Breast Cancer: Two

Decades of a Fascinating History and More to Come

Martine Piccart, M.D., Ph.D., Head, Medical Oncology, Jules Bordet

Institute; Chair, ESMO (European Society for Medical Oncology)

The talk will cover multiple aspects of anti-HER2 treatment in breast cancer.

It will present a summary of the clinical results obtained with trastuzumab

and several other anti-HER2 drugs in breast cancer (lapatinib, TDM1,

pertuzumab). Issues like the treatment duration, biomarkers of resistance

to treatment will be debated. Finally it will discuss future promising

research strategies: neoadjuvant trials, comparison between anti-HER2

agents, combinations of these drugs and functional imaging.

11:50 Antibody-Drug Conjugates: From Bench to Bedside and Back

Robert Lutz, Ph.D., Vice President, Translational Research & Development,

ImmunoGen, Inc.

Antibody-drug conjugates are emerging as an exciting approach to the

development of antibody-based therapeutics. The growing preclinical and

clinical experience with maytansinoid conjugates such as Kadcyla (T-DM1) is

leading to an enhanced understanding regarding critical attributes for target

antigens, antibodies, payloads and linkers. The translational knowledge

is being incorporated into research and development efforts for the next

generation of ADC candidates.

12:35 End of Cancer Biotherapeutics

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