Cancer drug discovery and development are effort- and cost-intensive processes that can take up to a decade or longer, moving through multiple stages—initial/de novo discovery, drug design and target validation, preclinical assessment, and clinical trials—before culminating in drug registration into the market.

This year’s three-part New Drugs on the Horizon sessions will provide an exciting behind-the-scenes glimpse of the inventive and state-of-the-art strategies in drug design and development in oncology.

Mary Mader, PhD, Vice President of Molecular Innovation at the Indiana Biosciences Research Institute and Chair of the American Association for Cancer Research Chemistry in Cancer Research (CICR) working group, said, “The AACR Annual Meeting is the biggest AACR-sponsored forum for earlier stages of drug discovery and development, where people are going to get an opportunity to view drug structures against particular proteins [of interest in cancer therapy] and obtain a high-level understanding of how research teams validated and interpreted their preclinical hypotheses.”

The New Drugs on the Horizon sessions are sponsored by the CICR working group, which encourages submissions from teams with data on agents that are entering phase 1 trials or have some phase 1 data to share, either in the New Drugs sessions or another session. These sessions highlight the advances that will set the stage for the next wave of cancer therapeutics. Mader said these sessions tend to attract cancer researchers who are interested in these target proteins/molecules and are trying to understand the relationship between drug structures and how the target-drug interaction modulates target biology.

Each year, the chairs of each of the New Drugs sessions solicit abstracts from a range of research groups, including small and large companies, that have a mandatory first disclosure of the structure of agents that are under active investigation in cancer clinical trials.

Rather than organizing each New Drugs session around a specific class of drug or tumor type, Mader said that each of the sessions is put together to offer insights into a diversity of modalities—small molecule inhibitors, proteolysis targeting chimeras (PROTACs) or molecular glue-type protein degraders, bispecific antibodies, antibody-drug conjugates (ADCs), and radioligands—to provide the audience a holistic view of the drug design and clinical development process. She added, “We are hoping that these sessions bring excitement not just in the structure, but also around how teams of researchers assemble the pieces of drug development, from identifying the target molecule or protein, formulating their hypotheses, developing assays and preclinical models, evaluating proofs of concept, and proposing their rationale for clinical safety, tolerability, and efficacy of the agent.”

Mader said the audience has an interest in first-in-class agents, which have a unique and/or novel mechanism of action, and best-in-class drugs—follow-on drugs of classes with an established mechanism of action that can solve class-specific issues or address challenges, such as target selectivity, brain penetrance in a tumor type that has a tendency to metastasize to CNS, or route of administration.

Mader concluded, “For me, it is a highlight to see those solutions being brought forward for patients. It makes what we do more meaningful.”

This year, the first two New Drugs on the Horizon sessions will take place Sunday, April 7, followed by a final session on Monday, April 8. In each session, abstract presentations will be followed by a discussion segment.

This year’s lineup of novel drugs includes a natural killer cell and T-cell engager, a direct KRAS G12C inhibitor, a brain-penetrant molecular glue-type protein degrader, a WRN helicase inhibitor, an ADC, a radioligand, highly selective CDK inhibitors, and agents with best-in-class potential.

---

New Drugs on the Horizon: Part 1 

Sunday, April 7, 1 – 2:30 p.m. PT
Ballroom 20 CD, Upper Level, Convention Center

ND01: ABBV-303: A novel NK and CD8 T cell engager specific for c-Met-expressing tumors; presenter, Jennifer Stone
ND02: Discovery of BMS-986365, a ligand-directed androgen receptor degrader (AR LDD) with a dual mechanism-of-action and best-in-class potential, for the treatment of advanced prostate cancer; presenter, Shuichan Xu
ND03: Discovery of RMC-9805, an oral, covalent tri-complex KRASG12D(ON) inhibitor; presenter, John E. Knox
ND04: Discovery of ORIC-944, a novel inhibitor of PRC2 with best-in-class properties for the treatment of prostate cancer; presenter, Lori S. Friedman

This session is co-chaired by Mader and Benjamin L. Ebert, MD, PhD, FAACR, George P. Canellos, MD, and Jean S. Canellos Professor of Medicine at Harvard Medical School and Chair of Medical Oncology at the Dana-Farber Cancer Institute.

---

New Drugs on the Horizon: Part 2

Sunday, April 7, 3 – 4:30 p.m. PT
Ballroom 20 CD, Upper Level, Convention Center

ND05: The discovery of ARV-393, a potent, orally bioavailable BCL6 targeting PROTAC® for the treatment of Non-Hodgkin’s Lymphoma; presenter, Dan Sherman
ND06: First disclosure of AZD8421, a highly selective CDK2 inhibitor to address resistance to CDK4/6 inhibitors in breast and CCNE1-high cancers; presenter, Christopher R. Denz
ND07: BBO-8520, a first-in-class, direct inhibitor of KRASG12C (ON), locks GTP-bound KRASG12C in the state 1 conformation resulting in rapid and complete blockade of effector binding; presenter, Pedro J. Beltran
ND08: M3554, a novel anti-GD2 antibody drug conjugate; presenter, Christiane Amendt

This session is co-chaired by Lori S. Friedman, PhD, Chief Scientific Officer of ORIC Pharmaceuticals, Inc., and Hong Shen, PhD, Head of China Innovation Center of Roche.

---

New Drugs on the Horizon: Part 3

Monday, April 8, 10:15 – 11:45 a.m. PT
Ballroom 20 CD, Upper Level, Convention Center

ND09: Actinium-225 -PSMA-Trillium (BAY 3563254): Preclinical evaluation and clinical imaging study of a novel 225Ac-labeled PSMA-targeting small molecule triad for the treatment of mCRPC; presenter, Sabine Zitzmann-Kolbe
ND10: NST-628 is a novel, potent, fully brain-penetrant MAPK pathway molecular glue that inhibits RAS- and RAF-driven cancers; presenter, Klaus P. Hoeflich
ND11: Chemoproteomic-enabled discovery of VVD-214, a synthetic lethal allosteric inhibitor of WRN helicase; presenter, Piergiorgio Pettazzoni
ND12: Discovery of PF-07220060, a potent and selective CDK4 inhibitor; presenters, Lars Anders and Gary Gallego

This session is co-chaired by Michelle R. Arkin, PhD, Professor of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco and Ingo Hartung, PhD, Director and Head of Medicinal Chemistry GER, Merck Healthcare KGaA.