News from AACR 2024: Sunday’s highlights

San Diego

The American Association of Cancer Research (AACR) Annual Meeting launched on Sunday 7 April in San Diego with an Opening Plenary Session showcasing cutting-edge technological advances opening new frontiers in cancer science.

The session ‘Inspiring Science, Fueling Progress, Revolutionizing Care’ featured a distinguished panel of cancer scientists who described evolving and emerging technological advances – from cell atlases and artificial intelligence-based biomarkers to proteomics and bioorthogonal chemistry – that are driving new discoveries and new directions in cancer research.

Aviv Regev, Head and Executive Vice President of Research and Early Development at Genentech, opened the session with a discussion of how advances in genomic sequencing are fostering the development of data-rich cell atlases and what that data could mean for new insights into cancer biology and novel therapeutics.

Jakob Nikolas Kather, Professor of clinical artificial intelligence at Technical University Dresden in Germany, then discussed how AI applications can be used to derive prognostic and predictive information from routine pathology slides.

Following this, Benjamin Cravatt, Professor and the Norton Gilula Chair in Biology and Chemistry at The Scripps Research Institute, discussed activity-based protein profiling (ABPP) and its use in discovering drug candidates for cancer-relevant proteins.

Carolyn Bertozzi, the Baker Family Director of Stanford ChEM-H, the Anne T and Robert M Bass Professor in the School of Humanities and Sciences, and Professor, by courtesy, of Chemical and Systems Biology and of Radiology at Stanford University, concluded the presentations with a discussion of glycobiology and next-generation cancer therapies enabled by bioorthogonal chemistry, which refers to high-yielding chemical reactions that proceed rapidly and selectively in biological environments without interfering with a molecule’s normal functions.

Outstanding Achievement Award

Pfizer Chairman and CEO Dr Albert Bourla received the 2024 AACR Outstanding Achievement Award for Service to Cancer Science and Medicine on behalf of Pfizer during the Opening Ceremony.

Pfizer is being honoured for its long-standing and impressive work in oncology, its deep-rooted commitment to scientific innovation in the development of novel cancer therapeutics, and its steadfast and enduring commitment to the AACR.

In December 2023, Pfizer announced that it had chosen to donate the rights of its royalties from the sale of Bavencio (avelumab) in the United States to the AACR, as an acknowledgment of the AACR’s dedication to sustained innovation in cancer research and treatment.

In addition to this donation, Pfizer has partnered with the AACR for many years to support impactful research and further the careers of eminent cancer scientists and physicians. The company has participated in, and made possible, numerous AACR scientific meetings and think tanks where leaders from the national and international cancer research community have disseminated their novel findings.

“On behalf of the AACR Board of Directors, I have the great honour to recognise Pfizer, and Dr Bourla as its Chairman and CEO, with this richly deserved award,” said Margaret Foti, Chief Executive Officer of the AACR. “Pfizer’s sustained and ongoing contributions to progress against cancer are an inspiration to the entire cancer research community.”

Research highlights
Bold Therapeutics

Dr Do-Youn Oh’s group at Seoul National University College of Medicine, Seoul, South Korea, presented on the use of Bold Therapeutics’ BOLD-100 in combination with ATR (Ataxia telangiectasia and Rad3-related protein serine/threonine kinase) inhibitors as anticancer therapies for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC).

Bold Therapeutics’ BOLD-100, a ruthenium-based small molecule, acts by targeting GRP78 to modulate the unfolded protein response (UPR) and by generating reactive oxygen species (ROS) leading to DNA damage and cell cycle arrest. This dual action triggers cell death across a spectrum of cancer types, including those resistant to current treatments. As a result, BOLD-100 holds promise for significantly enhancing treatment outcomes in several both solid and liquid tumours when used alongside other anticancer treatments.

In the study, the combination of BOLD-100 with the ATR inhibitor AZD6738 exhibits a synergistic effect, suggesting GRP78/ATR dual targeting as a promising therapeutic approach for PDAC.

“DNA repair mechanisms play a crucial role in maintaining genomic integrity, leading to cell cycle arrest and thereby preventing the uncontrolled growth and progression of cancer cells. Our in-vitro and in-vivo findings indicate that combining BOLD-100 with ATR inhibition results in synthetic lethality against highly aggressive Pancreatic Ductal Adenocarcinoma. We are eager to delve deeper into this research path and its potential clinical utility,” stated Dr Oh.

Ichnos Glenmark Innovation

Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences and Glenmark Pharmaceuticals, shared pre-clinical data for its oncology asset ISB 2001, which is currently being tested in a Phase I clinical trial in relapsed/refractory multiple myeloma (r/r MM).

The presentation showcased the results of ISB 2001 anti-myeloma activity in bone marrow aspirates from patients who were either newly diagnosed or suffer from r/r MM following multiples lines of treatment, including patients relapsing after CD38 and BCMA targeted therapies.

The pre-clinical study shows the promise of ISB 2001 trispecific antibody targeting BCMA and CD38 against multiple myeloma, and CD3 on T cells.

ISB 2001 showed superior cytotoxicity in comparison with teclistamab, alnuctamab and EM-801 across cell lines with variable expression levels of both BCMA and CD38.

“We are thrilled to present our preclinical findings for ISB 2001 at AACR,” said Lida Pacaud, Chief Medical Officer of Ichnos Glenmark Innovation. “The development of ISB 2001 holds special significance for us as it is crafted utilising our cutting-edge BEAT antibody engineering platform, a cornerstone of our pioneering approach to create innovative multispecific treatments for blood cancers and solid tumours.”

Innovent Biologics

Innovent Biologics presented preclinical data on multiple novel bispecific antibodies as well as antibody-drug-conjugates (ADCs) from its oncology pipeline.

In the poster session ‘IBI3001: a potentially first-in-class site-specific glycan-conjugated B7-H3/EGFR bispecific ADC for multiple solid tumors’, Dr Kaijie He, Vice President of Innovent, shared data which showed strong anti-tumour efficacy in vitro and in vivo across multiple solid tumours and is well tolerated with the therapeutic index at 40.

In the poster session ‘IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumours’, Dr He discussed study results for IBI334, which showed better tumour growth inhibition in vitro and in vivo than EGFR monoclonal antibody and c-met/EGFR bispecific antibody benchmarks.

Finally, ‘Discovery and preclinical characterization of IBI343, a site-specific glycan-conjugated anti-Claudin18.2 ADC for treating solid tumours’ demonstrated Claudin 18.2-specific in vitro cytotoxicity on a series of cancer cell lines at varying levels of target expression, and potent in vivo efficacy in multiple xenograft models.

Dr He said: ” With careful design and optimisation, our molecules can achieve favourable therapeutic windows of 40 to more than 200 times. We look forward to their performance in clinical settings and hope that these innovations can eventually benefit cancer patients.”

Diana Spencer, Senior Digital Content Editor, DDW

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