Immune therapies reshaping standard of care


Dr Alan Korman is the Vice President of Immuno-Oncology (I-O) Discovery at Bristol-Myers Squibb Global. He spoke to BiotechDispatch on a recent trip to Australia, during which he met with oncologists and researchers to discuss the company's I-O portfolio.

He trained as a molecular immunologist at Harvard and MIT in Cambridge, Massachusetts, including working with Richard Mulligan, who is often described as the ‘father of gene therapy’.

Dr Korman says he explored a range of career opportunities, including a research position at the Institut Pasteur in Paris, before deciding to join industry.

His first position in industry was at a Denver-based biotechnology company, which, after merging with Nexstar Pharmaceuticals, initiated a project looking at I-O therapies, specifically CTLA-4.

Further mergers and takeovers during the 1990s eventually led Dr Korman to Medarex. He says Medarex initiated research programs looking at PD-1 and PD-L1, which would ultimately emerge as one of the most exciting oncology breakthroughs in living memory.

According to Dr Korman, PD-1 acts as a ‘brake’ on the T-Cell’s anti-cancer activities. Inhibiting PD-1 showed early promise as a way to release T-Cells to attack a cancer.

“We were believers but didn’t fully appreciate the potential of PD-1,” says Dr Korman.

“We knew they had the potential to be transformative because they were taking a different approach to cancer therapy - treating the host rather than the tumour. The drug was not the drug – the T cell is the drug - we were ‘potentiating’ the development and potency of the immune system.

“Nobody really appreciated the full potential until we started the multi-dose dose escalations and seeing activity in clinical trials, particularly in melanoma, renal and lung cancer,” he adds.

Following early collaboration with Medarex on CTLA-4, Bristol-Myers Squibb acquired the biotech company in 2009. In the process, it acquired full rights to its development portfolio, which at the time included now PBS-listed melanoma therapy YERVOY (ipilimumab).

Dr Korman continued with Bristol-Myers Squibb after the takeover and has nothing but praise for the Company and its support for ongoing research at the former Medarex research site in California.

“They are actually investing to expand the site,” he says.

Bristol-Myers Squibb is one of the leaders in I-O, with OPDIVO (nivolumab) set to be considered by the Pharmaceutical Benefits Advisory Committee (PBAC) at its upcoming meeting.

Dr Korman says the Company is currently conducting around 50 clinical trials in I-O, targeting over 30 cancer types in around 8,000 patients

Other companies are also investing in I-O, with nine trialing agents targeting PD-1 or PD-L1.

One of the other emerging insights from the trials of I-O therapies has been the need to reassess the standard of care.

“What's happening at a scientific level is leading to a re-evaluation of the standard of care for cancer, which for such a long time has been based on chemotherapy. There is evidence that some chemotherapy might prevent the T-Cell from functioning.

He says the potential of combinations will be one of the most significant developments in the years ahead.

“PD-1 will be the pillar of all combinations because of its activity and superior adverse event profile,” says Dr Korman. “Our challenge will be to identify which combination of T-Cell agents will get the broadest efficacy with the best adverse event profile.”

He points to the Company’s combination of OPDIVO and CTLA4 anti-body YERVOY.

The PBAC will consider the combination for the treatment of advanced melanoma at its next meeting.