Cambridge Healthtech Institute’s Eleventh Annual 

Translational to Clinical R&D

Strategies and Technologies to Reduce Attrition and Improve Clinical Outcomes

February 16-18, 2015 | Moscone North Convention Center | San Francisco, CA
Part of the 22nd Annual Molecular Medicine Tri-Conference

 

Despite the many breakthroughs in high-throughput omics, a deeper understanding of disease biology, and increased investments in R&D, the delivery of innovative therapies to patients in need has rapidly declined—with significant clinical hurdles during transition from phase II to III. Effectively and efficiently translating novel science into clinical settings has the potential to accelerate the development of new medicines, while increasing the odds of success throughout clinical research. Yet, how do developers find practical ways to overcome the translational challenges resulting in high rates of attrition? What are emerging modalities poised to deliver highly efficacious and safer therapies? What strategies derived from novel science and technologies are improving the translation from benchtop to bedside?

Cambridge Healthtech Institute’s Translational to Clinical R&D is designed to convene thought leaders working in early discovery and development to bring forth emerging strategies for improving therapeutic intervention, increasing R&D efficiency using novel science and technologies, and ultimately ensuring the right therapy is developed for the right target and reaches the right patients in need.


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Monday, February 16

10:30 am Conference Program Registration


IMPROVING TRANSLATION &
SUCCESS OF ADCs IN THE CLINIC
 

11:50 Chairperson’s Opening Remarks

Lynn Zieske, Ph.D., Principal Scientist, Life Science, Singulex Inc.

12:00 pm FEATURED PRESENTATION: Development of ADCs at Seattle Genetics

Jonathan Drachman, M.D., CMO & Executive Vice President, Research and Development, Seattle Genetics

In this presentation I will highlight the strategy for testing ADCETRIS in earlier lines of therapy & new indications for lymphoma. I will also discuss recent preclinical discoveries that may potentially increase ADC stability and potency in the future.

12:30 Target, Drug and Linker Selection Strategies for Antibody-Drug Conjugates

Hans-Peter Gerber, Ph.D., Vice President, BioConjugates Discovery & Development, Oncology Research Unit East, Pfizer Worldwide Research and Development

1:00 Session Break

1:15 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

2:15 Session Break


IMPROVING TRANSLATION &
SUCCESS OF ADCs IN THE CLINIC (CONT.)
 

2:30 Chairperson’s Remarks

Hans-Peter Gerber, Ph.D., Vice President, BioConjugates Discovery & Development, Oncology Research Unit East, Pfizer Worldwide Research and Development

2:40 Emerging Strategies to Improve Success with ADCs in Oncology

Robert Lutz, Ph.D., Vice President, Translational Research and Development, ImmunoGen

Our growing clinical experience with antibody-maytansinoid conjugates is leading to an enhanced understanding regarding critical attributes for their success.This presentation will highlight some recent efforts to incorporate this translational knowledge into the future development of these compounds.

3:10 Tuning the Efficacy of Antibody Drug Conjugates via Site-Specific, Linkable Amino Acids

Alan Wahl, Ph.D., Vice President, Research and Discovery, Ambrx, Inc.

The random linkage of drugs to targeting proteins is now eclipsed by new chemistries allowing both a defined number of drugs, multiple coupling options and selective drug positioning on the antibody surface. Using a medicinal chemistry approach varying the reacting amino acid, and its position, linkage chemistry and warhead, an ADC of superior stability, potency and tolerability can be realized. Production cell lines engineered to incorporate reactive, non-natural amino acids into optimal sites on the antibody surface now yield homogeneous, readily linkable antibodies amenable to multiple drug/coupling strategies.

3:40 Translational Safety of Immunostimulatory and ADC Cancer Biologics

Rakesh Dixit, Ph.D., DABT, Vice President, R&D; Global Head Biologics Safety Assessment, Pathology and LAR, MedImmune (AstraZeneca Biologics)

With technological advances in generation of immune-stimulatory and chemically armed biologics, the translational safety and toxicology predictions face unprecedented challenges. There is now renewed focus on a better understanding of translational immune-pharmacology associated toxicities (both on-target and off-target). Translational case studies with major considerations such as target distribution, target pharmacology, and systemic pharmacokinetics, early screening, both traditional and non-traditional (e.g., transgenic models), and in vitro safety assessments will be addressed.

4:10 The Search for Mutant HTT Protein in Huntington's Disease Patient CSF Using the Erenna Immunoassay System

Douglas Macdonald, Ph.D., Director, Drug Discovery and Development, CHDI Foundation / CHDI Management

Huntington protein (HTT) suppression is a key therapeutic strategy for Huntington’s disease (HD).  We have developed a sensitive and selective assay that measures polyglutamine-expanded HTT protein using the Singulex Single Molecule Counting technology that displays increased sensitivity over other assays.

4:25 Sponsored Presentation (Opportunity Available)

4:40 Break and Transition to Plenary Session

5:00 Plenary Session

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day


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Tuesday, February 17

7:00 am Registration and Morning Coffee

8:00 Plenary Session

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing


CONSIDERATIONS FOR DEVELOPMENT OF IMMUNOTHERAPIES AND COMBINATIONS 

10:05 Chairperson’s Remarks

James F. Smothers, Ph.D., Senior Director& Head, Discovery, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

10:15 Biomarkers in Cancer Immunotherapy

Ira Mellman, M.D., Vice President, Cancer Immunology, Genentech

Recent advances in cancer immunotherapy differ from other developments in oncology therapeutics in several respects. Not only have immunotherapies proved remarkably promising, but also the underlying science promises to be largely driven by findings in the clinic. Thus, both patient selection and the discovery of new therapeutic opportunities will be dependent on the ability to identify, collect, and understand biomarkers and immunobiology of patient response and lack of response.

10:45 Strategies for Clinical Development of Cancer Immunotherapy

Roy Baynes, M.D., Senior Vice President, Global Clinical Development, Merck

It has been established that autoimmunity against a number of malignancies can be revealed by pharmacologic modulation of checkpoint inhibitors and co-stimulatory molecules. A strategic imperative is comprehensive definition of the efficacy and safety of monotherapy across tumor types. This has required understanding the limitations of standard response evaluations and the need to identify and appropriately manage immune mediated adverse events. Patient selection and study enrichment approaches are emerging. Informative biology will be required to evaluate the array of potential therapeutic combinations.

11:15 Translational Approaches for the Development of Intratumoral Immunotherapies.

Robert Pierce, M.D., CMO, OncoSec Medical, Inc.

Intratumoral therapies are capable of reversing local immunosuppressive mechanisms and driving systemic anti-tumor immune responses. Given the safety and potential systemic efficacy of this approach, Intratumoral therapies will likely play a growing role in future combination immunotherapy regimens. The pros and cons of current syngeneic mouse models will be addressed with particular emphasis on unique aspects of intratumoral therapies.

11:45 Preclinical Validation of Immunotherapies and Combination Strategies for Cancer

James F. Smothers, Ph.D., Senior Director, Head, Discovery, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

Recent clinical strategies to modulate T cell checkpoint pathways have demonstrated significant patient benefit in melanoma, renal cell carcinoma and non-small cell lung cancer indications. Clinical successes with immuno-oncology medicines greatly depend upon animal disease model studies and other pre-clinical rationale for their development. Likewise, the value for combinations of immunotherapies with other therapies depends on pre-clinical demonstration of the predictive value for potential patient benefit. Many immunotherapy targets are poorly conserved at the amino acid level between rodents and humans which often forces application of surrogate studies with syngeneic cancer models to evince value of immunotherapies in cancer. Genetically Engineered Mouse models and “humanized” models that incorporate human PBMCs into Severe Combined Immunodeficiency mice have also been used to validate efficacy and mechanism of action studies ahead of immunotherapy development in a clinical setting. Translational data coupled with pre-clinical results can further bridge understanding of what patient populations might gain the most benefit from an immuno-oncology experimental medicine alone or in combination with another agent(s).

12:15 pm Session Break

12:25 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


T-CELL IMMUNOTHERAPY SPOTLIGHT 

2:00 Chairperson’s Remarks

Richard A. Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio

2:10 CAR T Cell Therapy: Target Antigen Discovery and Clinical Translation

Richard A. Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio

This talk will emphasize the importance of tumor antigen discovery in the selection of targets in CAR T cell therapy. As examples, I will compare and contrast Her2/neu and EGFRvIII as solid tumor targets. I will also discuss the clinical translation of these two CAR-based therapies and discuss options for building the next generation of CAR T cell technologies.

2:40 The Emerging Role of Autologous Tumor-Infiltrating Lymphocytes (TIL) as a Superior Immunotherapy Option for Patients with Solid Tumors

Laszlo Radvanyi, Ph.D., CSO, Lion Biotechnologies

Although a number of T-cell based therapies are being developed for solid tumors, autologous TIL therapy has the longest clinical experience and is still the one of the most powerful immunotherapy options for patients with advanced solid tumors. This presentation will describe TIL therapy for solid tumors, its advantages compared to other current cell therapy options, its strategic role as part of a growing immunotherapy “toolbox” for personalized care of metastatic cancer, and the development of predictive biomarkers to identify resistance mechanisms as novel targets for combination therapies.

3:10 Translational Strategies for Bispecific T Cell Engager (BiTE) Antibodies

Stanley R. Frankel, M.D., Medical Sciences Executive Medical Director, Oncology Early Development, Therapeutic Area Head, Amgen

3:40 Sponsored Presentations (Opportunities Available)

4:10 Mardi Gras Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

6:00 Close of Day


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Wednesday, February 18

7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Plenary Session Panel

9:45 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


ADVANCES IN IMAGING FOR
TRANSLATABLE BIOMARKERS
 

10:35 Chairperson’s Remarks

Paul J. McCracken, Ph.D., Director, Imaging Biomarkers and Personalized Medicine, Eisai

10:45 Imaging for Decision Making in Drug Discovery and Early Development

Paul McCracken, Ph.D., Director of Imaging, Biomarkers and Personalized Medicine CFU, Eisai

In this presentation, I will discuss improving the quality of compounds and decision making in discovery and early development with fit-for-purpose imaging biomarkers. I will provide case studies in neurology and oncology for application of imaging biomarkers to the discovery pipeline, including molecular target engagement, antibody-drug conjugate imaging, proof of mechanism, efficacy, stratification and drug safety.

11:15 Using Zr-89 ImmunoPET in the Selection, Understanding, and Early Clinical Development of Antibody-Drug Conjugates

Simon Williams, Ph.D., Principal Scientist, Biomedical Imaging, Genentech

This presentation will review the development of Zr-89 immunoPET as a technology that is particularly well-suited to demonstrating, in patients, the combination of target presence, tissue penetration and internalization which are three requirements for effective antibody-drug conjugates. The use of immunoPET in quantifying drug delivery to tumor tissue will be discussed along with limitations of immunoPET and a discussion of complementary experiments.

11:45 Advances in Preclinical Imaging to Enable the Translation of Novel Therapies

Charles Glaus, Ph.D., Senior Scientist, Research Imaging Sciences, Amgen

12:15 pm Session Break

12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:00 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing


PREDICTIVE PRECLINICAL MODELS: Assessing specificity, toxicity & resistance in immunotherapy 

1:40 Chairperson’s Remarks

Jennifer Brogdon, Ph.D., Senior Investigator, Oncology Cell and Immunotherapies, Novartis Institutes for BioMedical Research, Inc.

1:50 CART Therapy: Preclinical Approaches to Assess Specificity and Efficacy

Jennifer Brogdon, Ph.D., Senior Investigator, Oncology Cell and Immunotherapies, Novartis Institutes for BioMedical Research, Inc.

Due to the unique sensitivity of CAR therapy to low levels of antigen, understanding the specificity of a given CAR is critical to managing the safety and potential toxicity risk in patients. In this presentation, I will discuss our efforts to understand the safety and specificity of an EGFRvIII-specific CAR therapy that is being developed for Glioblastoma Multiforme. Highlights will include our in vitro and in vivo preclinical assessment of our humanized EGFRvIII CAR as well as the study design of the Phase I trial.

2:20 T Cell Biology in a 3D Cell Culture System

David Colter, Ph.D., Principal Scientist, Biologics Research, Janssen

We have developed a high-throughput, 3D lung tumor model system for target discovery and drug screening applications. Specifically, we characterized the phenotypic, functional and drug response differences between lung tumor cells grown as 2D monolayer cultures, versus cells grown as 3D spheroids. We are currently extending the utility of this 3D model system towards evaluating antibody-mediated T cell recruitment and subsequent T cell-mediated cytotoxicity.

2:50 Mechanisms of Resistance to Antibody-Drug Conjugates

Frank Loganzo, Ph.D., Director, ADC Biochemistry, Oncology, Pfizer

The molecular mechanisms of drug resistance vary significantly across cancer indications, and there are limited data on the acquisition of resistance to ADCs. We have generated pre-clinical models of ADC resistance by chronic exposure of cancer cell lines with ADCs. Leveraging the modular nature of ADCs, we have observed that changes to the linker and/or payload can overcome acquired resistance to some ADCs, both in vitro and in vivo, suggesting that patients whose tumors become refractory to one therapy may respond to other ADCs, or to chemotherapeutics with similar mechanisms of action.

3:20 Sponsored Presentations (Opportunities Available)

3:50 Refreshment Break


ADVANCES IN BIOMARKER DEVELOPMENT
IN ONCOLOGY
 

4:00 Chairperson’s Remarks

Jae Lee, Ph.D., Chair and Senior Member, Biostatistics and Bioinformatics, Moffitt Cancer Center

4:10 Identifying and Overcoming Markers of Chemoresistance

Jason Baum, Ph.D., Associate Director, Companion Diagnostics, Research, Merrimack Pharmaceuticals

This talk will focus on the understanding of cancer cell survival networks to identify key biomarkers of resistance to chemotherapy. This includes initial proof-of-concept in a preclinical setting and translation into the clinic through the development of both tissue and blood-based diagnostic assays.Data from phase 2 clinical studies will illustrate the resistance of biomarker positive patients to chemotherapies across multiple indications, and the potential for targeted therapies to overcome this resistance.

4:40 The Impact of Tumor Heterogeneity on Clinical Biomarker Development Using FFPE Tissue

Ken Chang, Ph.D., Senior Principal Scientist, Molecular Biomarkers and Diagnostics, Merck Clinical Labs

We have developed a “Concordance Calculator” to quantify reproducibility of multi-variant calls among Next Generation Sequencing. Recently we applied this approach to study the impact of tumor heterogeneity among consecutive FFPE tissue sections across entire tumor block and found no heterogeneity among different sections/regions of tumors in terms of mutation profiles using NGS. These studies suggest that DNA mutation signatures as novel biomarkers for cancer diagnosis and prognosis are likely to be less sensitive to the impact of tumor heterogeneity than RNA-based expression signatures.

5:10 Prognostic Surrogate Markers for Survival, A Case Series for a Novel Antiangiogenic Therapy

M.A. Nezami, M.D., President, Cancer Epigenetics, Pacific Medical Center of Hope

Establishing the prognosis in majority of patients, especially with heterogeneous tumors, has been extremely challenging. One area of most recent attention in identifying surrogate markers for survival has been the vasculogenesis and its related serum markers. Here we present a series of cases treated with a novel antiangiogenic therapy and monitored through these markers to identify response that translated to prognosis and survival.

5:40 Close of Conference Program



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2015 MMTC Final Agenda 

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