ASCO 2025: A glimpse into the future of cancer care?

As often the case in oncology, novel mechanisms of action for medicines have taken center stage at this year’s American Society of Clinical Oncology (ASCO) annual meeting in sunny Chicago. This is the largest medical conference on the calendar, with Bellevue Asset Management’s portfolio manager, Dr. Terence McManus, on the ground speaking with doctors about new innovation in cancer treatment. Over the last few days, we would point to three emerging technologies that have caught attention:

• Firstly, bispecific antibodies - which are designed to engage more than one cancer-killing target - have really exploded in terms of the range of targets.
• Secondly, another mechanism of action which has seen a significant broadening at this meeting is the antibody-drug conjugate (ADC) space. ADCs use an antibody to focus chemotherapy directly to the tumour. These act like guided missiles, with a rocket and a warhead. We have seen multiple novel targets for ADCs emerge at the meeting.
• Lastly, we would point to the use of artificial intelligence (AI) in oncology – for both diagnosis and treatment selection - is starting to move into the clinical practice.

Within biopharma, continuous innovation is essential to push the boundaries of science, deliver better treatments for patients, and refresh portfolios to ensure growth through patent expires of blockbuster drugs. This process was very evident at this year’s ASCO meeting, driven by the large current incumbents and young biotech’s from across the globe.

As a result of the developments at the meeting, we have increased conviction in some of our portfolio holdings. With US healthcare reform overhangs and fear near peak levels (in our view), valuations for biopharma are at historically low levels. Looking beyond the political noise, innovations like those we have seen at ASCO reinforce a healthy long-term outlook for the sector.

Further details below:

Will blockbuster drug Keytruda be unseated by bispecifics? – Maybe
Over the last few days, we have seen updates across multiple tumour types on a new drug mechanism, VEGF-PD1 bispecific monoclonal antibodies, which combine two previously validated targets.

VEGF-PD1 bispecific monoclonal antibodies from Pfizer (via 3SBio licensing deal), BioNTech (via its acquisition of Biotheus), and Summit/Akeso have shown intriguing data. PD-1 antibodies such as Merck & Co's Keytruda have been central to the development of immune-oncology (using the body’s immune system to kill cancer cells) over the last 10 years. VEGF antibodies, such as Roche's Avastin, have been around for even longer, and starve tumours of blood supply. Giving patients both of these drugs has not really worked in the past, but combining them in one single drug seems to be different. Doctors we spoke to at ASCO were impressed with the progression free survival data shown by several of these bispecific drugs so far. Indeed, in a bid to catchup with peers, Bristol Myers announced a partnership with BioNTech on Monday morning (USD 1.5 bn upfront with USD 2 bn in noncontingent anniversary payments through 2028, and eligible to up to USD 7.6 bn in milestones).

While we are still far from having the full picture, and we look forward to mature overall survival data (an early look at overall survival with one drug was disappointing), we see the potential for Merck & Co's USD 29 bn (FY 2024 sales) PD-1 antibody Keytruda, to be unseated from its crown in some tumour settings. Merck & Co is also pursuing this bispecific combination, but remains at a much earlier stage with an asset acquired through the USD 3 bn  acquisition of LaNova.

Beyond VEGF, other bispecific approaches which include PD-1 were on display at the meeting. These included PD-1/IL-2 alpha from Innovent, and PD-1/TGF-beta from Sino Biophama.

Along with the exciting new mechanism of action, another remarkable aspect of these development programs is the number of Chinese companies involved in the development of this corner of cutting-edge oncology – including 3SBio, Biotheus, Akeso, LaNova, Innovent, Sino Biopharma.

Antibody-drug conjugates – guided missiles to kill cancer
Another mechanism of action which has seen a significant broadening in recent years is in the antibody-drug conjugate (ADC) space. ADCs use an antibody to focus chemotherapy directly to the tumour. These act like guided missiles, with a rocket and a warhead. At the meeting, there were updates on TROP2-, IB,  PD-L1-, and B7H3-directed ADCs from Merck & Co (TROP2), AstraZeneca/ Daiichi Sankyo (TROP2), Gilead (TROP2), Pfizer (IB-, PD-L1) and BioNtech (B7H3) among others.

For example, Gilead's TROP-2 ADC, Trodelvy, received a positive reception from doctors at the meeting. The ASCENT-04 study showed convincing benefit when used in combination with Keytruda in first-line PD-L1-positive triple-negative breast cancer (TNBC) patients. TNBC is one of the most difficult to treat tumour types.

In prostate cancer, we were also impressed by BioNTech's BNT324 (B7H3 directed) which showed strong cancer activity in an early-stage trial. 

AI at an oncology conference
We saw several presentations highlighting the growing role of AI in cancer care. For example, AstraZeneca has used AI to create an diagnostic computational pathology approach (called quantitative continuous scoring, QCS) which can identify patients whose cancer has a specific marker called TROP-2. At the meeting, retrospective data showed that this method could identify a specific patient subgroup and potentially improve patient outcomes. However, this approach is somewhat cumbersome and would require changes to current clinical workflows. As a result, the jury is still out on this biomarker, and we wait for prospective data.