Every year, billions are spent on cancer research, but only a very small percentage of new drugs and treatments reach patients. Armand de Gramont, co-founder and CSO of Onward Therapeutics, a clinical-stage oncology drug company, spoke to us about the field as it currently stands and what he’d like to see moving forwards.

Tell us about your professional background and what led you to co-found Onward Therapeutics.

First of all, I am a biochemist by training: I did a PhD at Paris VI, after which I went to Bethesda, Maryland for five years to work at the National Institute of Health. I then decided to move into drug development, joining a small contract research organisation with a hybrid business model in Paris, before moving to Lausanne to work at the CHUV under George Coukos. After two years, I transitioned into a biotech company based in Taiwan that successfully developed and registered a major oncology drug still used to treat pancreatic cancer, before finally deciding to leverage all these experiences and co-found Onward Therapeutics in 2019.

At Onward Therapeutics, we focus on taking promising oncology treatments from the laboratory through Phase 1 and Phase 2 clinical trials – we say that this is our ‘sweet spot’. We select a handful of drug candidates to take to clinical trials and then, once the trials are complete, our objective is to license out to bigger commercial pharma companies, which take the products to the next stage. We are pretty agnostic about therapeutic modality: our aim is to bring products to the clinic and find where they fit best into the overall treatment landscape.

Do you have any specific criteria for selecting products? How easy is it to know what’s going to have legs so early in the process?

We don’t have a crystal ball, so we don’t know for certain what will be successful. The rate of attrition (the percentage of drugs that fail at each stage of the development process) for oncology treatments is very high: less than 1% of the drugs in pre-clinical development make it to market. And then, only between 3% and 5% of the oncology drugs that start a Phase 1 trial will get to the market. So one of the main criteria for us is the likelihood that a product will reach the clinic.

We are very pragmatic, as we know that this is a challenging and highly specialised field. Notably, we work with a network of key opinion leaders in oncology who challenge our ideas and targets. And then we ask ourselves questions like: Which types of cancer could the drug candidate target? Will it come with a risk of toxicity? Will it be hugely complex to manufacture? We want to give ourselves (and future patients) the best chance of success.

Are there trendy products that you’re seeing at the moment and/or that you are particularly interested in investing in? How do you assess them in terms of where the market is going?

In the field of oncology, the two main therapeutic modalities in cancer research are currently antibodies and small molecules; if you look at registered products on the market, most of them are antibodies and small molecules. At the same time, cell therapies, oligonucleotides and vaccines are emerging. With all this in mind, three years ago, we decided to license in a bispecific antibody treatment, we acquired a cell therapy project and we also decided to support a research programme on small molecules. Our most advanced programme today is our bispecific antibody, which has reached the clinical stage.

When it comes to cell therapies, it is worth noting that they were quite popular until recently. Since then, however, investors’ interest has fallen because this type of product is very expensive and difficult to manufacture. The results in clinical trials have also been mixed. With this in mind, we have chosen to focus our investment on products, like non-engineered natural killer (NK) cells, that do not require us to add unnecessary steps or complications to the manufacturing process, making them more affordable per dose. The social context is such that neither funders nor patients may want to continue paying CHF 300,000 or 400,000 for a single dose of treatment.

You’re in a very interesting position, in that you have to be mindful of market demands but you also work in a field that has a huge impact on individual patients’ lives. It must be a difficult balance to strike. How do you conceive of Onward Therapeutics’ role in this landscape and where would you like to see the cancer research market go in the next few years?
 
As I said before, we adopt a pragmatic and step-by-step approach. We want to take the best and most effective products to the clinic and show their potential benefits – and as fast as possible, without compromising quality. For reference, we were able to get a Phase 1 clinical trial approved for our bispecific antibody treatment within just two years, which is well below the usual expected timeline. By streamlining the money and time we spend on each product, we can fast-track its journey through manufacturing and preclinical testing, meaning it reaches prospective patients that bit sooner.

All of us have loved ones who have been touched by cancer, and we just want to give them the best chance possible. Which leads me onto what I’d like to see in the future, if possible: more drugs reaching patients. For example, some products have been shown to produce decent benefits in trial, but their regulatory journey is fraught with difficulty because they don’t represent a major breakthrough, just a small step forward. But small steps add up, and they also offer both patients and physicians more options in the fight against this disease. Never mind that they are often more cost-effective – groundbreaking science comes with big expense. Still, I don’t make the rules!