Inaugural

Safety and Efficacy of Bispecific Antibodies, ADCs and Combination Therapy

January 19 - 20, 2023 ALL TIMES PST

The Inaugural Safety and Efficacy of Bispecific Antibodies, ADCs and Combination Therapy at the PepTalk Summit will review clinical successes and milestones of emerging constructs and novel formats for these important assets in the drug development arsenal. The safety and efficacy of bispecifics and ADCs will be examined for molecules in development, and strategies and trends will be shared that address and mitigate toxicity issues. The selection of targets and cancer killing immune effector cells and payload determine many of the safety parameters and will be given full consideration. Join us to explore this critical area of biologics as we set out to chart a course for ensuring the safety of these novel formats.

Thursday, January 19

Registration and Morning Coffee (Indigo and Aqua Foyer)8:00 am

Organizer's Welcome Remarks8:30 am

ROOM LOCATION: Aqua Salon D

RECENT ADVANCES IN BISPECIFIC, ADCs, AND THEIR COMBINATIONS

8:35 am

Chairperson's Opening Remarks

Rakesh Dixit, PhD, President & CEO, Bionavigen

8:40 am KEYNOTE PRESENTATION:

Efficacy and Safety of Bispecifics, ADCs, and Combination Therapies in War against Deadly Cancers

Rakesh Dixit, PhD, President & CEO, Bionavigen

In the last 10 years, innovations in cancer research have delivered many effective therapies to combat deadly cancers. Immunotherapies, ADCs, and their smart combinations have emerged as three pillars of cancer therapies. This keynote presentation will discuss the advances made in bispecific immunotherapies, ADCs, and combination therapies. The special focus will be on the safety challenges of cancer therapies that affect both their effectiveness and the quality of life. 

9:20 am

Cevostamab, a FcHR5xCD3 Bispecific Antibody for the Treatment of Relapse/Refractory Multiple Myeloma 

Suzanne M. Trudel, MSc, MD, Affiliate Scientist, Medicine, Princess Margaret Hospital

Fc receptor-homologue 5 (FcRH5) is a cell surface antigen of unknown function that is selectively expressed in late B cells and enriched on malignant plasma. Cevostamab (BFCR4350A), is a humanized IgG Fc antibody, targeting FcRH5 and CD3 on T cells that is undergoing clinical evaluation in relapsed/refractory multiple myeloma. Preclinical data supporting the clinical application of this novel bispecific antibody in multiple myeloma as well as the safety profile and efficacy in relapsed/refractory disease will be discussed.

9:50 am Novel Format Conjugates and Multi-Specific Antibodies Produced by Chemical Site-Specific Conjugation: AJICAP

Yutaka Matsuda, PhD, Project Manager, ADC, Ajinomoto Bio-Pharma Services

Site-specific chemical conjugation technology (termed AJICAP®) is a simplified manufacturing process without using antibody engineering. We attempted to use site-specific conjugation technology to produce bispecific and trispecific antibodies with a new shape. The development of the unique methodology to produce homogeneous DAR = 1 conjugates enabled the production of homogeneous multispecific antibodies without a difficult purification process. Initial applications of AJICAP technology to novel format conjugates are also discussed.

Coffee Break in the Exhibit Hall with Poster Viewing (Indigo Ballroom)10:20 am

11:00 am

Amivantamab – EGFR x cMet  Bispecific Antibody with the Activities that Show 1 + 1 > 2

Mark L. Chiu, PhD, CSO, Tavotek Biotherapeutics

A review of amivantamab, a bispecific antibody (BsAb) targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) pathways, will be presented. Specific focus on patients with non-small cell lung cancer. The unique mechanisms of action can provide benefits to patients with malignancies associated with aberrant EGFR and MET signaling.  A new generation molecule using cMet x EGFR x VEGF will be highlighted for unmet medical needs.

11:30 am

Trispecific Antibodies

Ronnie R Wei, PhD, Head, Biologics Discovery, Modex Therapeutics

Most diseases involve an interplay of multiple biological pathways.  Effective therapies for cancers and viral infections may require combinatorial intervention. Carefully designed strategies could elicit novel mechanisms to achieve better efficacy and/or improved risk/benefit. I will present how we achieved exceptional breadth and potency against HIV and SARS-CoV-2 in a single molecule using the trispecific antibody technology, which may lead to improved prevention and treatment approaches for these diseases.

Enjoy Lunch on Your Own12:00 pm

Ice Cream Break in the Exhibit Hall and Last Chance for Poster Viewing (Indigo Ballroom)1:10 pm

2:00 pm

Chairperson's Remarks

Rakesh Dixit, PhD, President & CEO, Bionavigen

2:05 pm

Tebentafusp: A Novel gp100-Directed TCR-CD3 Bispecific for the Treatment of Metastatic Uveal Melanoma

Koustubh Ranade, PhD, Head, Translational Medicine, Immunocore LLC

ImmTACs are bispecific proteins comprised of an affinity-enhanced T cell receptor recognizing tumor antigens in the context of HLA fused to a T cell-activating anti-CD3 domain. Tebentafusp, a gp100-directed immTAC, is the first TCR bispecific to demonstrate overall survival benefit in a solid tumor, and is approved for the treatment of metastatic uveal melanoma. I will discuss the mechanism of action of tebentafusp, factors associated with efficacy, and challenges and opportunities for TCR bispecifics and combinations.

EMERGING BISPECIFICS: SAFETY AND EFFICACY CHALLENGES

2:35 pm

On-Target Toxicity Associated with an Anti-CD70 Bispecific T Cell Engager Molecule in Cynomolgus Monkeys

Tod Harper, PhD, DABT Principal Scientist, Translational Safety, Amgen, Inc.

CD3 bispecific T cell engager molecules have great potential to treat cancer. Nevertheless, dependent on the targeted tumor antigen, the mechanism of action that drives efficacy may also contribute to on-target/off-tumor toxicities. Here we illustrate how a thorough understanding of expression and upregulation is needed to fully address putative liabilities associated with on-target/off-tumor activity of CD3 bispecific molecules using an anti-CD70 half-life extended BiTE molecule as a case example.

Networking Refreshment Break (Aqua Foyer)3:05 pm

3:30 pm

Bispecific Antibodies for Hematologic Malignancies: Clinical Development, Therapeutic Applications, and Recent Clinical Trials

Priya Hays, PhD, Technical Writer, Science Writer, Hays Documentation Specialists, LLC

Bispecific antibodies are composed of two monoclonal antibodies that engage T cells with tumor cell antigens and lead to tumor cell lysis. The most common types fall into the category of bispecific T cell engagers, or BiTEs, that have the canonical CD3-CD19 bispecific construct. Blinatumomab is the first bispecific antibody that received FDA approval for relapsed refractory B cell precursor acute lymphoblastic leukemia. Blinatumomab has been shown to have robust clinical outcomes and is associated with adverse events such as cytokine release syndrome and neurotoxicity. Other bispecific antibodies are under clinical investigation for multiple myeloma and acute myeloid leukemia.

4:00 pm

Teclistamab (BCMA x CD3 Bispecific) in Relapsed/Refractory Multiple Myeloma

Carlyn Tan, MD, Hematologic Oncologist, Hematology & Oncology, Memorial Sloan Kettering Cancer Center

Teclistamab is a novel BCMA x CD3 T cell-redirecting bispecific antibody developed for the treatment of multiple myeloma (MM). We will review the safety and efficacy of teclistamab as a single agent and in combination with various standard myeloma regimens from recent clinical trials, describe strategies to manage teclistamab-specific toxicities and side effects, and discuss challenges and future approaches for RRMM with the development of multiple BCMA-directed therapies.


Close of Day4:30 pm

Friday, January 20

Registration (Indigo Foyer)7:30 am

ROOM LOCATION: Indigo and Aqua Foyer

BuzZ Sessions

8:00 amBuzZ Sessions with Continental Breakfast

PepTalk’s BuzZ Sessions are focused, stimulating discussions in which delegates discuss important and interesting topics related to upstream protein expression and production through downstream scale-up and manufacturing. This is a moderated discussion with brainstorming and interactive problem-solving between scientists from diverse areas who share a common interest in the discussion topic.
Please continue to check the BuzZ Session page on our conference website for detailed discussion topics and moderators.

BuzZ Table 6: Bispecific Antibodies from Bench to the Clinic

Priya Hays, PhD, Technical Writer, Science Writer, Hays Documentation Specialists, LLC

  • Clinical development and efficacy of BiTEs and BCMAs in hematologic malignancies
  • Immune related adverse events 
  • Beyond CD3-CD19 epitopes: Dual affinity BsAbs and tandem diabodies 
  • Combination and sequential therapies ​​

BuzZ Table 7: The Challenges and Opportunities for Treating Low HER2 Expressing Cancers

Rakesh Dixit, PhD, President & CEO, Bionavigen

Robert J. Lutz, PhD, CSO, Iksuda Therapeutics

  • Challenges of developing effective therapies against low HER2-cancers
  • Unprecedented activity of Enhertu (Trastuzumab Deruxtecan), a HER2 targeting ADC in low HER2 breast cancer, ASCO recognition and FDA approval
  • New and upcoming therapies to treat Enhertu refractory low HER2 expressing tumors​

ROOM LOCATION: Aqua Salon D

INNOVATIVE ADCs: MITIGATION OF TOXICITY TO IMPROVE EFFICACY

9:00 am

Chairperson's Remarks

Rakesh Dixit, PhD, President & CEO, Bionavigen

9:05 am

Novel Tumor-Selective ADC Designs for Improved Therapeutic Index

Robert J. Lutz, PhD, CSO, Iksuda Therapeutics

Novel linker-payload chemistries take advantage of upregulated enzymes in cancer cells to improve the tumor-selectivity of ADC activation. Increased tumor-selectivity allows the exploration of high potency payloads to improve efficacy and tolerability. Case studies demonstrating marked differentiation of the new ADC designs compared to traditional ADC benchmarks will be presented.

9:35 am

A CD79b Targeting ADC with Superior Anti-Tumor Activity and Tolerability

Bernd Schlereth, PhD, Chief Development Officer, Araris Biotech AG

The Araris’ site-specific and 1-step linker conjugation technology aims at generating safe and highly potent ADCs without the need for antibody engineering prior to linker-payload conjugation. We developed a very stable anti-CD79b-MMAE ADC with this technology that showed a remarkable activity at low doses in pre-clinical models and which could be dosed 8x higher in non-human primates compared to polatuzumab-vedotin. Our ADC may represent a safe and efficacious option for the treatment of patients with diffuse large B cell lymphoma (DLBCL) and indolent lymphoma.

10:05 am

Making Amanitin Available for the Clinic – Engineering a Therapeutic Window into a Poison

George Badescu, PhD, Chief Business Officer, Heidelberg Pharma AG

Amanitin is a member of the amatoxin group of natural poisons, which occur in the death cap mushroom (Amanita phalloides). Amanitin has a unique biological mode of action which could be used as the basis for developing highly effective, innovative drugs. It works by inhibiting RNA polymerase II, which results in apoptosis.  The inhibition of RNA polymerase II facilitates killing of dormant tumor cells (CSCs, TICs) and offers new treatment options for difficult-to-treat cancers and high-risk patients. Our strategy is to use an ADC approach to engineer a therapeutic window into amanitin. The first amanitin-based ADC (HDP-101) is directed against BCMA and is currently undergoing clinical development for multiple myeloma.

Networking Coffee Break (Aqua Foyer)10:35 am

11:00 am

Protein Engineering of Avidity Effects to Improve the Therapeutic Window of Antibody Drug Conjugates

Greg M. Thurber, PhD, Associate Professor, Chemical Engineering & Biomedical Engineering, University of Michigan

Antibody Drug Conjugates (and Bispecific Antibodies) interact with their targets, including immune cells, through multivalent interactions with receptors. These interactions can be designed computationally and tested experimentally to develop enhanced therapies. Here, we discuss how these multivalent interactions, also known as avidity affects, can be tuned with combination therapy to improve intratumoral drug distribution and target specificity for increased efficacy and reduced toxicity.

11:30 am PANEL DISCUSSION:

Learning from the Successes and Failures of ADCs, Bispecifics, and Combinations

PANEL MODERATOR:

Rakesh Dixit, PhD, President & CEO, Bionavigen

ADCs and bispecific immunotherapeutic agents have revolutionized cancer treatment. Immunotherapy–ADC combinations have the most potential value in tumors with highly mutated neoantigens, which can be released by the cytotoxic killing of tumors with highly-targeted ADCs. The deserted immune tumors that are insensitive to immunotherapy can be transformed by ADCs incorporating cytotoxic drugs, immune agonists, cytokines, etc. The major challenge facing ADCs in combination with immunotherapeutic agents is how to minimize a steep threshold in toxicity and a poor understanding of how these agents should be sequenced with immunotherapeutic agents. The panel discussion with  Q&A  will include learnings from the successes and failures of ADCs, bispecifics, and their combinations.

PANELISTS:

Nimish Gera, PhD, Vice President, Biologics, Mythic Therapeutics

Tod Harper, PhD, DABT Principal Scientist, Translational Safety, Amgen, Inc.

Greg M. Thurber, PhD, Associate Professor, Chemical Engineering & Biomedical Engineering, University of Michigan

Carlyn Tan, MD, Hematologic Oncologist, Hematology & Oncology, Memorial Sloan Kettering Cancer Center

Close of Safety and Efficacy of Bispecific Antibodies, ADCs, and Combination Therapy12:30 pm