Ten years after successful approval, immuno-oncology is ready for the next revolution

Checkpoint inhibitors have defined the emergence of immuno-oncology. One notable example is Merck’s Keytruda, a PD-1 inhibitor that is the top-selling drug in the U.S. with annual sales of $25 billion across more than 30 indications. Its first FDA approval in 2014 marked a revolutionary moment in immuno-oncology and PD-1 inhibitors, followed by a frenzy of investment and research.

Having been part of that first wave at Bristol-Myers Squibb and currently leading Mural Oncology in advancing cytokine-based immunotherapies, I believe this 10-year anniversary is an appropriate time to recognize the enormous impact of the first immuno-oncology (IO) revolution. have had an impact on patients and herald the arrival of a second wave of I/O that will go even further toward realizing the potential of this class.

Moving past the plateau

In the early days of IO, I had the opportunity to help lead research and development at BMS, including a dramatic expansion of the oncology portfolio. Through this expansion, I became actively involved in the development of IO BMS’s strategy, from its early days of immunotherapy through the development and development of a broad portfolio, including Opdivo, which was approved shortly after Keytruda.

This period was a revolutionary time in the field of cancer and AI. As an industry, we have gained a greater understanding of the biology and role of the immune system in cancer treatment, allowing us to develop new treatments that have had a profound impact on cancer treatment. We had never before seen a disease response in which tumors seemingly melted away – this has truly changed the understanding and expectations of what is possible to treat cancer.

However, in the world of drug development, we often see more failures than successes. Although indications for the use of PD-1 inhibitors and combinations involving them have rapidly expanded, this success has remained almost unique in AI. The industry has made huge investments in finding complementary and complementary I/O pathways that can be used as monotherapy or in combination, but progress has been very limited. And today, response rates to AI treatment stabilized at about 30% the overall response rate among patients, which, although incredible, means that 70% of patients do not respond.

A decade without another major I/O success has led to cynicism in the segment thanks to oncology investments. fall from 46% of asset-focused venture funding in 2021 to 22% in 2022. Many are skeptical that a comeback is in the works. However, I believe that what we are seeing is simply the natural evolution that occurs in every therapeutic area.

The first generation of breakthroughs and the work based on them show that science in general is nonlinear. From class after class of new therapeutics, we see that it often takes at least 10 years to bring a new class to market. and the development of more effective agents. We are now approaching the end of this 10-year arc of IO therapy, where a greater understanding of the underlying biology, coupled with new science and opportunities to exploit that understanding, will lead to a new wave of approvals.

Immuno-oncology 2.0

While the first wave of the IO revolution was led by big pharma players, this time I believe it will be the smaller biotech companies that will drive the next wave of treatments and push the boundaries of what we think is possible in cancer. Small and mid-sized biotech companies can move quickly and nimblely when fielding candidates. This next wave will be driven by consideration of additional pathways beyond PD-1, as we now have a greater understanding of underlying disease biology across a wide range of cancers and tumor types.

BispecificityThe IO field, which has been around for over a decade, is potentially a $50 billion market. Renewed confidence in the sector is driven by the promise of increased efficacy, reduced toxicity and personalized treatment approaches. We saw a lot of attention on these drugs and antibody-drug conjugates (ADCs) during ESMO this year. promising data on ovarian cancer. ADCs, another popular modality, are on the rise. similar turning pointwith the rapid increase in the number of approved drugs for the treatment of hematological cancers and solid tumors, leading to investment growth to meet the growing demand for targeted therapies that could provide higher efficacy and fewer side effects.

I have seen how the first generation of AI therapy has helped change the lives of patients. I joined Mural because I still believe that only the first chapter of IO’s story has been written. Many analysts and investors are also sensing a shift and renewing their enthusiasm for IOs, and we’ve also heard enthusiasm from doctors and the broader research community. For decades, the potential of cytokines in IO has been well studied but not yet realized. With advances in protein engineering, there is a real opportunity to improve on all previous work and overcome some of the previous limitations. While it is unlikely that we will see another major treatment like PD-1, I believe that we will see the emergence of new classes of drugs that will change the lives of patients, such as cytokines, T-cell activators and other multispecific antibodies.

As we reflect on the key role of checkpoint inhibitors in AI, it becomes clear that we are on the threshold of a new transformative phase. The first AI revolution changed the paradigm of cancer treatment, introducing treatments that significantly extended life and changed expectations. Moving forward, remember: IO’s story has not yet been fully written, and the next chapter is just beginning.