From 5-10 April 2024 in San Diego, the cancer research community gathered for the annual meeting of the American Association for Cancer Research (AACR). DDW’s Megan Thomas spoke with biotech and pharma leaders to understand more about the cancer research landscape. 

An event of this size provides a wide-angle lens through which innovators can not only present their own work but learn about the work being carried out by their peers. 

Key takeaways 

The mission of the AACR is to prevent and cure cancer through research, education, communication, collaboration, science policy and advocacy, and funding for cancer research. Dr Alexandra Sapetschnig, Group Leader at STORM Therapeutics, described the event as one that “really set the agenda for oncology research in 2024” through the display of new approaches and methods that are expanding opportunities in drug development. “This bodes well for potential future research and therapies,” she adds. Moreover, Martin Drysdale, Chief Scientific Officer at NeoPhore, commented on seeing research into microsatellite instability so high on the agenda, with several studies shedding light on how cancers with this biomarker interact with immunotherapy.

The AACR has more than 58,000 members residing in 141 countries and territories, and the 2024 conference attracted over 22,000 attendees. Dr András Strassz, Chief Medical Officer at Heidelberg Pharma, noted an extensive schedule, which featured a wealth of conferences, courses, forums, and workshops over the six days, which he says proved to be “a rich source of information on oncology.” Additionally, Ariceum Therapeutics’ Head of Translational Biology & Non-Clinical Pharmacology, Anika Jäkel, also described the conference agenda as “truly diverse,” which covered “many forms of therapeutic approaches, with some revelatory findings about new biomarkers that could lead to a new generation of personalised therapies.”

Data and presentations

All posters at the AACR Annual Meeting 2024 were presented in-person. Ariceum was presenting a poster demonstrating findings on the discovery of novel macrocyclic peptide radioligands for tumour therapy by mRNA display. The poster was in collaboration with the company’s research partner, the global pharmaceutical company UCB, and the findings describe the selection and initial characterisation of macrocyclic peptides against an undisclosed target discovered using UCB’s mRNA-display technology platform, ExtremeDiversity. The company’s poster explained how macrocyclic peptides, potent ligands for radioligand therapeutics, can selectively deliver radioisotopes to cancer tissues to eradicate tumour cells while limiting the damage to surrounding tissues.

András Strassz expressed that at Heidelberg Pharma, the goal is to make Amanitin available as a cancer therapy. To support this goal, Heidelberg Pharma presented safety and first efficacy data from the Phase I/IIa clinical trial with lead ATAC product candidate HDP-101 as well as preclinical data on other drug candidates from the company’s proprietary antibody-drug conjugate (ADC) technology platforms. These data showed promising first objective responses in relapsed and refractory multiple myeloma.

Meanwhile, NeoPhore’s focus was presenting key data from its lead MMR program at the Novel Therapeutics and Preclinical Models session, while STORM was there for a presentation about first-in-class inhibitors of the tRNA methyltransferase (METTL1) for the treatment of cancer. Sapetschnig said that STORM will continue to develop a pipeline of therapies inhibiting RNA modifying enzymes and advance this candidate towards clinical development. 

LRK-A is an oral, highly potent, and specific heterobifunctional protein degrader which is targeting the lipid kinase PIP4K2C, on which Larkspur Biosciences’ CEO Catherine Sabatos-Peyton, shared a poster presentation that showed evidence of how PIP4K2C functions as a cancer-intrinsic driver of immune evasion in human tumour and immune cells. It also shows efficacy for low doses of LRK-A as a monotherapy, and LRK-A drives anti-tumour activity in colorectal cancer (CRC) patient samples, including complete tumour regressions, in a CRC mouse model. 

On the other hand, a poster on the discovery of selective BRM (SMARCA2) ATPase inhibitors for the treatment of BRG1 (SMARCA4) mutant cancers was shared by Foghorn Therapeutics’ CEO Steven Bellon. The therapy, FHD-909, is a potential first-in-class oral BRM (SMARCA2) selective inhibitor being evaluated for non-small cell lung cancer (NSCLC). BRG is frequently mutated in cancer, including in approximately 10% of NSCLC carcinomas. Selective inhibition of BRM is a mechanism by which BRG1-mutated cancer cell growth would be affected by losing BRM function, while normal tissues should be spared as they still express functional BRG1.

AACR 2024 marked the first time Mural Oncology had disclosed preclinical data from their IL-18 and IL-12 programmes. The company is working to assemble functional IL-12 in the tumour with goals of avoiding toxicity associated with systemic exposure and maximising the IL-12 therapeutic window. CEO Caroline Loew shared two posters, which explained the limited clinical efficacy due to IL-18BP tightly binding to IL-18, neutralising IL-18 receptor activation. As such, Mural Oncology is working to design an engineered IL-18 with a half-life extension and resistant to IL-18BP neutralisation, while retaining native IL-18 activity.

Celularity presented in vivo data from its T-cell therapy platform, which highlighted the potent anti-tumour efficacy of PT-CD16VS in combination with Trastuzumab against HER2+ gastric cancer tumour cells. Importantly, the anti-tumor effect was selective for the HER2 expressing cancer cells with no killing of the healthy cells expressing low levels of HER2. These data suggest that PT-CD16VS, with its universal CD16 receptor approach, offers the potential to be combined with various  monoclonal antibodies targeting multiple cancers.

A network of innovators 

The exchange of ideas, research, results, and insight make AACR not just an informative event in the cancer research industry but also one that embraces community. It is no surprise that so many within this network consider it a focal point of their year, fostering networks that drive forward the future of cancer research.

From DDW Volume 25 – Issue 3, Summer 2024 Read the digital issue