Antibody-drug conjugates are a drug class with a robust pipeline and a flurry of deal-making among pharmaceutical companies. With more than 30 ADCs currently in various stages of clinical trials, and even more in preclinical and/or are ready to enter
first-in-human trials, the market is rife with eager anticipation of the data coming out from ADCs currently in the clinic.
Join CHI’s Fifth Annual ADCs: Preclinical and Clinical Updates conference to hear strategies,
results and learnings from early ADC clinical trials, as well as the preclinical package and translational considerations when preparing to enter the clinic.
THURSDAY, MAY 7
12:00 pm Registration
12:35 Luncheon in the Exhibit Hall with Poster Viewing
1:40 Chairperson’s Remarks
Pamela A. Trail, Ph.D., Vice President, Oncology, Regeneron Pharmaceuticals
1:50 KEYNOTE PRESENTATIONS
ADCs: Building on the Past, Delivering on the Present and Optimizing for the Future
Clay B. Siegall, Ph.D., President, CEO and Chairman of the Board, Seattle Genetics, Inc.
Antibody-drug conjugates represent an increasingly important therapeutic approach for the treatment of cancer, with two ADCs currently approved by the FDA and dozens of other programs progressing through clinical trials and preclinical development.
This presentation will highlight ADCETRIS® (brentuximab vedotin) and other ADCs in development. In addition, advances in ADC technology will be discussed.
2:20 Optimizing ADC-Based Therapies in Cancer
John Lambert, Ph.D., Executive Vice President and Distinguished Research Fellow, ImmunoGen, Inc.Our growing clinical experience with antibody-maytansinoid conjugates is leading to an enhanced understanding regarding critical attributes for their success. This presentation will highlight a recent clinical/translational R&D effort leading to a change in the treatment paradigm of an ADC.
2:50 Antibody-Drug Conjugates: Translational Considerations
Isabel Figueroa, Ph.D., Principal Scientist, DMPK and Disposition, Biologics Discovery Operations, MRL Biologics
Antibody-Drug Conjugates (ADCs) are increasingly employed as novel targeted therapies. ADCs combine the exquisite selectivity of targeted antibodies and high potency of small molecule drugs with the aim in achieving the desired therapeutic objectives.
Successful strategies for the development of the lead ADC candidates will require comparative investigations and integration of knowledge with respect to target- and modality-related considerations across species. Here, we have attempted to address
some of the key translational considerations critical for early development of ADCs in an integrated fashion.
3:20 Select Poster Presentation:
Development of Pluripotent Specific Antibodies for Novel Cancer Therapeutics
Yawen Ju, Ph.D., Scientist, CureMeta, LLC.
Over 90% of cancer deaths are due to metastasis. CureMeta’s goal
to develop ADCs is driven by the hypothesis that metastatic cancers are caused
by embryonic/pluripotent cancer stem cells. Using new antibodies developed
internally, we have demonstrated that our target is specific to pluripotent
stem cells and highly expressed in metastatic cancers. In addition, we have
used these antibodies to develop potent ADCs as potential novel cancer
therapeutics.
3:35 Refreshment Break
4:20 Problem-Solving Breakout Discussions
Overcoming Drug Resistance in Next Gen ADCs
Moderator: Alan C. Rigby, Ph.D., VP, Antibody-Drug Conjugate Biology, Eli Lilly and Company
- Strategic thoughts on resistance
- Identifying responders and resistant populations
- Defining resistance- functional targets vs OE targets
- Combinations that prevent/overcome resistance
Design of Effective ADCs: With Over 30 ADCs in the Clinic, What Have We Learned?
Moderator: Pamela A Trail, Ph.D., VP, Oncology, Regeneron Pharmaceuticals
There are currently two approved
ADCs and more than 30 in various stages of clinical evaluation. This breakout
session will explore what has (or has not) been established as guiding
principles for design of safe and effective ADCs, approaches to advancing ADCs
to the clinic and considerations in clinical trial design.
Characterization of Novel Linkers-Payloads on ADCs
Moderator: Janet Wolfe, Ph.D., President & Founder, Wolfe Labs, Inc.
- What molecular properties of novel linkers and payloads have the potential to compromise ADC critical quality attributes?
- What analytical and biophysical characterization techniques need to be applied to de-risk these novel linkers and payloads?
- Are there specific analytical techniques that can yield insight into degradation and destabilization pathways?
5:20 End of Day
5:15 Registration for Dinner Short Courses
FRIDAY, MAY 8
8:00 am Morning Coffee
8:30 Chairperson’s Remarks
Alan Rigby, Ph.D., Vice President, Antibody-Drug Conjugate Biology, Eli Lilly and Company
8:35 Preclinical Development of IGN786: A Homogeneous Antibody-Drug Conjugate Directed Against C16orf54 for the Treatment of Hematological Malignancies
Jason Damiano, Ph.D., Director, Discovery Research, Igenica Biotherapeutics
Using Igenica’s proprietary proteomics-based target discovery technology, C16orf54 was identified as a novel cell-surface antibody target. C16orf54 is overexpressed with high prevalence in primary CLL and AML tumor specimens and has restricted
expression in normal tissues. Using Igenica’s proprietary SNAP technology, a homogeneous ADC directed against C16orf54 was developed. The IGN786 clinical candidate is highly efficacious in C16orf54-expressing xenograft models.
9:05 Advances in ADC Development at Pfizer Oncology
Puja Sapra, Ph.D., Senior Director, Oncology Research Unit, Pfizer, Inc.
This presentation will highlight the innovations made in Pfizer in terms of development of novel linker-payloads, conjugation chemistries and target identification for ADC development. Case studies will be used to elaborate on the multifaceted
optimization required to yield a viable clinical candidate. Highlights from late stage preclinical and clinical ADCs will be discussed including candidates targeting tumor-initiating cells and Notch pathway. Finally, translational biology
and combination strategies to enable clinical development of ADCs will be discussed.
9:35 Molecular Integrity of Antibody-Drug Conjugates: Applying Preclinical Learnings to the Clinic
Brooke Rock, Ph.D., Senior Scientist, Pharmacokinetics and Drug Metabolism, Amgen, Inc.
Characterizing the mechanisms of ADC instability and release of free cytotoxin are germane in the design of ADCs. Understanding the mechanism behind release of the cytotoxin is important in both the efficacy of the ADC as well as toxicity
profile. Factors affecting the ADC stability will be reviewed and the subsequent impact on ADC disposition will be considered in the context of clinical monitoring.
10:05 Coffee Break
10:35 mAbXcite: A Novel Immunotherapy Platform that Initiates a Robust Anti-Cancer Immune Response by Recruiting and Activating Neutrophils
Ifat
Rubin-Bejerano, Ph.D., Co-Founder and CSO, ImmuneXcite, Inc.
mAbXcite is a platform that exhibits a lasting immune response that is initiated by neutrophils. mAbXcite constructs of two validated antibodies, trastuzumab and cetuximab, as well as a syngeneic antibody demonstrate significantly greater
efficacy in resistant tumor models. Mice that show complete regression or stasis do not grow tumors upon rechallenge, suggesting a memory response that is initiated by neutrophils.
11:05 Engineering and Clinical Development of Antibody-Targeted Nanotherapeutics
Daryl C. Drummond, Ph.D., Vice President, Discovery, Merrimack Pharmaceuticals
The use of nanotherapeutics provides a novel and highly effective platform for developing next generation antibody-drug conjugates. These novel immunotargeted nanotherapeutics are engineered with the antibody indirectly conjugated through
the lipidic carrier, and with a wide range of possible payloads. An ErbB2-targeted pegylated liposomal doxorubicin is currently showing promising preclinical and early clinical activity, and is currently being evaluated in a Phase II trial
in metastatic breast cancer.
11:35 Toward Clinical Development of the Novel HER2-Targeting Antibody-Drug Conjugate SYD985
Patrick Groothuis,
Ph.D., Principal Scientist, Preclinical Pharmacology, Synthon Biopharmaceuticals B.V.
SYD985 is a novel anti-HER2 antibody-drug conjugate (ADC) based on the monoclonal antibody trastuzumab, a cathepsin B-sensitive dipeptide linker (valine-citrulline (vc) motif) and a unique prodrug seco-duocarmycin-hydroxybenzamide-azaindole.
In vitro and in vivo studies exemplify that SYD985 is a promising therapeutic modality for cancer patients with moderate or even low HER2 levels in tumors.
12:05pm Anti-Tumor Activity of the Antibody-Drug Conjugate (ADC), BT-062, Against CD138-Positive Solid Tumors
Kurt Schönfeld, Ph.D., Manager, Research Immunology, Global Research, Biotest AG
BT-062 is an ADC comprising a chimeric anti-CD138 antibody conjugated to the maytansinoid DM4. CD138 has long been recognized as being highly expressed on multiple myeloma (MM), and findings previously reported include BT-062’s highly selective cytotoxic activity against CD138-positive MM cells. Here, we show the potential of BT-062 as a treatment for CD138-positive solid tumors.
12:35 Luncheon Presentation (Sponsorship Opportunity Available)
or Enjoy Lunch on Your Own
1:05 Refreshment Break
1:35 Chairperson’s Remarks
Alan Rigby, Ph.D., Vice President, Antibody-Drug Conjugate Biology, Eli Lilly and Company
1:40 pm Clinical Results with SN-38-Conjugated Antibody-Drug Conjugates in Patients with Metastatic Solid Cancers
David M. Goldenberg, Sc.D., M.D., CSO, Immunomedics, Inc.
2:10 Clinical Perspective of ADC Development
Michael K. Bauer, Ph.D., Senior Vice President, Clinical Development, Genmab
- Mechanism of action of HuMax-Tissue Factor-ADC
- Translation of preclinical research into the clinic
- Striking the right balance between patient safety and charting unknown clinical territory
- Beyond dose-escalation
- Patient selection - why, when and how
2:40 Clinical Development of Auristatin-Based ADCs at Seattle Genetics
Nancy Whiting, Pharm.D., BCOP, Executive Director & Head, Medical Affairs, Seattle Genetics
In addition to a broad clinical development program with Seattle Genetics’ approved ADC ADCETRIS® (brentuximab vedotin), the company has multiple other auristatin-based ADC programs as well as novel pyrolobenzodiazepine dimer-based
ADCs in its pipeline. This talk will highlight novel auristatin-based ADCs in development with a focus on recent clinical data.
3:10 Tumor Selective Anti-EGFR Antibody-Drug Conjugates for Multiple Indications
Ed Reilly, Ph.D., Senior Research Fellow, Project Director, Oncology Discovery, Abbvie
Most approved EGFR antibodies are unsuitable for use as antibody-drug conjugates (ADCs) because of on target toxicities. We have developed EGFR-directed ADCs that bind to a tumor selective epitope thereby limiting the effects of the
toxin on normal cells while maintaining a high degree of activity on EGFR-overexpressing tumor cells. Early promising clinical data, including durable objective responses, in subjects with EGFR-positive tumors will be presented.
3:40 AGS67E, An Anti-CD37 Monomethyl Auristatin E (MMAE) Antibody-Drug Conjugate for NHL, CLL & AML
Leonard M. Reyno, M.D., Senior Vice President and Chief Medical Officer, Agensys, Inc.
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.
4:10 End of Conference