Before taking on the role of CEO at Bluesphere Bio Inc., David Apelian would have said the most exciting work he’d done in immuno-oncology had been at Globeimmune Inc., where he’d served as chief medical officer for more than a decade, working in the field of cancer immunotherapy “back when no one believed the immune system would be something we could leverage against cancer.”

After two years of record venture capital financing, which peaked during the first quarter of 2021 with a whopping $38.27 billion raised, investments in biopharma have started to drop off, and industry watchers are expecting a slower deal pace ahead. The same is expected for the IPO market, which saw a record 134 companies go public in 2021. Those trends, combined with big pharma’s hefty cash balances, could mean an M&A surge in 2022, though the availability of special purpose acquisition companies could continue to offer private firms an attractive alternative to a buyout.

Despite big wins in precision oncology – such as last year’s accelerated FDA nod for Amgen Inc.’s Lumakras (sotorasib) in KRAS G12C-mutated locally advanced or metastatic non-small-cell lung cancer – industry has barely scratched the surface of the field’s potential. Part of the problem is on the scientific front. Only about a third of patients are currently eligible for targeted therapy, since the majority of patients “do not have a known therapeutic vulnerability for which we have a drug match,” Keith Flaherty, director of clinical research at Massachusetts General Hospital, said during a Feb. 14 session at the BIO CEO & Investor Conference. “And that’s a big problem.”

These days it’s nearly impossible to turn around in the biopharma world without hearing about how some company is going to use machine learning to revolutionize drug development. “It really is a catchphrase,” acknowledged Jo Viney, whose latest startup, Seismic Therapeutic Inc. launched with a $101 million series A round to advance a platform incorporating machine learning capabilities to find new drugs for autoimmune diseases.

Gilead Sciences Inc. is making a one-time $1.25 billion payment, with a commitment for a royalty that analysts predict could add as much $1.5 billion more, to Viiv Healthcare Ltd., in a deal designed to resolve all global pending or potential patent infringement claims relating to sales of HIV drug Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide). The initial payment, recorded in the fourth quarter of 2021, put a significant dent in Gilead’s earnings per share but removes the uncertainty of a trial outcome and clears the way for future bictegravir-containing products.