Adoram is a Swiss-based biotech spin-off from the University of Geneva, leveraging the advantages of allosteric biochemistry to create new treatments for patients with solid tumors or immune-based diseases.
Small molecule drugs represent an emerging class of immunotherapies to boost the immune system in cancer patients and regulate the immune system in inflammatory or auto-immune disorders. Because only a subset of patients benefits from current cancer immunotherapies, alternative or combination immunotherapeutic approaches are essential to improve clinical response rates. Furthermore, there are still multiple solid tumor indications for which no adequate treatment exists, necessitating completely novel approaches to address these growing markets.
Asset 1: A2AR NAM small molecule, nearing clinical drug candidate stage. Excellent translational human in vitro responses, proof of mode of action in vivo in high-adenosine mouse models as a standalone immunotherapy.
Cancer immunotherapy with a difference
Adoram Therapeutics’ most advanced asset is a small molecule drug aimed at boosting the anti-tumor immune response in patients with a wide range of solid tumors, many of which do not have adequate therapies at the moment. Because the drug is aimed at enhancing the immune system to destroy tumor cells, it is known as an immunotherapy.
Some existing immunotherapies have already revolutionized cancer treatment regimens and extended the lives of countless patients. For example, anti-PD-1 or anti-CTLA-4 antibodies, collectively known as immune checkpoint blockade (ICB antibodies), represent a multibillion dollar market and are known to mediate beneficial effects in over 30% of cancer patients overall, with higher or lower success rates depending on the type of cancer. More recently, adoptive cellular therapies, e.g. CAR-T cells, use sophisticated and expensive ex vivo engineering or activation of a patient’s own immune cells, which are then infused to destroy the cancer cells.
For the patients who are not responding adequately to currently-approved immunotherapies, or who do not have access to complex cellular therapies, other solutions are urgently needed. Therefore, much effort is underway to improve existing immunotherapies and develop completely novel approaches that could be used as standalone (single-agent) or combination immunotherapies. One such approach is a small molecule immunotherapy, which has advantages over existing immunotherapies because it could be delivered orally as a pill (instead of intravenously), has simpler and more cost-effective drug manufacturing, and could more easily penetrate into solid tumors thanks to its smaller molecular size – which is a problem for biologics such as ICB antibodies and cellular therapies.
Our most advanced drug candidate is a small molecule negative allosteric modulator of the adenosine 2A receptor, or an ‘A2AR NAM’ for short. A2AR is known to be a key mediator of immunosuppression in solid tumors because it is present on many cancer-fighting immune cells (e.g. T cells and NK cells). Therefore the therapeutic modulation of this receptor would render the tumor immune environment more favorable for killing cancer cells. Allosterism is a much less commonly harnessed molecular mode of action in small molecule drug design. Allosterism is known to impart several advantages for patients in terms of both efficacy and safety, hence, we aim to develop a best-in-class therapy.
The A2AR NAM cancer immunotherapy program is being advanced by our Asset Creation Team as well as external collaborators, and is currently in preclinical testing. Adoram’s optimized lead molecules demonstrate excellent biological activity in translational human-cell based assays; already matching the current best-in-class clinical candidate and outperforming similar drugs that have made it to phase I or II human clinical trials.
Asset 2: A2AR PAM (positive allosteric modulator), 4 distinct hit series undergoing medicinal chemistry. Licensed to Adoram in 2022.
Niche allosteric drug screening capacity: A technology more sensitive than industry-standard cAMP-detecting assays, and adaptable to GPCR drug targets, the largest class of receptors in the human genome. Our in-house know-how and curated molecule libraries representing 6 million compounds are ready for rapid drug discovery to further populate our pipeline via biotech and pharma collaborations.
Adoram was incorporated in Geneva, Switzerland in June 2022, spinning off from the University of Geneva (UNIGE). We have executed an exclusive license agreement with UNIGE, providing exclusive rights to the A2AR NAM patent, A2AR PAM hit molecules, and the right to use the allosteric screening technology to generate further assets.
Our vision is towards a multi-asset company that harnesses the unique advantages of allosteric drugs: focusing on adenosine receptors for Adoram’s foremost assets (A2AR NAM immuno-oncology and A2AR PAM anti-inflammation), as well as future population of our discovery pipeline with GPCR drug targets for urgent unmet medical needs.
Asset perspectives. A2AR NAM: Deliver a formulated clinical candidate drug, CMC, pre-IND, Ph-lb/II asset exit. A2AR PAM: lead optimization, selection of clinical indications, option for co-development via strategic partnering.
By applying a unique molecular mode of action (allosteric modulation) to GPCR drug targets, Adoram Therapeutics aims to overcome several limitations of conventional (orthosteric / non-allosteric) small molecule therapies. For example, our negative allosteric modulator (NAM) of a clinically validated onco-immunology drug target, the adenosine 2A receptor (A2AR), is designed to be potent in highly immunosuppressive solid tumor microenvironments and have an improved safety profile over competitors.
Co-founder & CEO
David obtained a Ph.D. from The University of Melbourne in 2011, focusing on immunomodulators and vaccines for infectious diseases. His time working on cancer immunotherapies in industry at CSL solidified the intention to continue a carrier that would translate to new therapies for patients. After further postdoctoral experience in the Paris region while working on optimizing prime-boost strategies for vaccines, David began co-ordinating small research teams at the W.H.O. Centre for Vaccines in 2015, and subsequently in immunology and drug discovery laboratories at the University of Geneva, Switzerland. David led the asset creation team during the hit-to-lead drug discovery phase of Adoram’s foremost asset, a small molecule cancer immunotherapy, and assumed the position of CEO upon co-founding the company.
Co-Founder & CSO
Co-Founder, Advisor, & interim CFO
Prof. Leonardo Scapozza leads a laboratory of over 25 personnel in the Faculty of Science at UNIGE that is focussed on understanding ligand-macromolecule interactions to discover new therapeutic strategies in the areas of cancer, antibiotics, inflammatory and neglected/orphan diseases. His lab identifies new chemical entities and targets using an interdisciplinary approach based on the combination of biochemistry/biophysics and chemistry with computational chemistry/molecular modelling. His lab has extensive experience in the field of drug discovery, allowing in-house protein expression and purification, molecular modelling, medicinal chemistry, in vitro/in vivo pharmacology. Prof. Scapozza has over 130 peer-reviewed articles and 8 patents, three Phoenix prizes for innovative pharmaceutical chemistry (1996, 2001, 2012), and is a serial entrepreneur. Prof. Scapozza’s has successfully collaborated with research and clinical collaborators to bring a cancer drug repurposing study to Phase 3 clinical trials (PMID 23332367,). Prof. Scapozza will assume a 20% role in the company as interim CFO and drug development advisor.
CTO, Medicinal Chemistry
In silico drug design