Biotech is entering the hard work phase of immuno-oncology – Mammen on The BioCentury Show

With immuno-oncology struggling to go beyond first generation checkpoint targets and cell therapies, Mathai Mammen sees the industry as entering a hard-work phase to solve some of the critical issues. Some may take over a decade to sort out, and the solutions will partly lie in precision medicine, an approach Mammen sees as central to progress across the board, from neuropsychiatry to enabling global access to innovative medicines.

Mammen discussed his views on the industry and innovation on the latest episode of The BioCentury Show. Having recently left his role as EVP of pharmaceutical R&D at Johnson & Johnson (NYSE:JNJ), Mammen will become chairman, president and CEO of Fog Pharmaceuticals Inc., starting full time on June 12. He is currently special adviser and CEO designate. 

Acknowledging the successes of CTLA-4 and PD-1 inhibitors, and the demonstration that the immune system can be deployed to treat cancer via those agents, bispecifics, CAR Ts and other modalities, Mammen said the next step of leveraging immune mediators and finding new brakes and accelerators gets increasingly complex.

“What companies across the ecosystem are seeing is that there’s different reasons in different contexts,” for why some tumors respond and others don’t, and how to turn a cold tumor hot. “There’s not going to be one magic solution,” said Mammen. “We’re going to see different experiments try different things.” 

“We’re entering the hard work phase” of immuno-oncology, he said. For example, although microsatellite instability (MSI) and tumor mutation burden are a start, it’s clear the immune system needs to see several antigens to effectively respond to a tumor. “How do you know which antigens to promote might depend on your HLA context as a person with the tumor.”

Having precision biomarkers for immuno-oncology “doesn’t really exist right now in a high stringency way,” said Mammen. Likewise, it’s early days with CAR T cells, and the role of different T cells in efficacy and unwanted side effects is going to take years to play out. 

Mammen also sees precision medicine as core to progress in neuropsychiatry, an area that has been underserved and underinvested in compared with its sister field neurodegeneration, despite the large unmet need.

The issue, said Mammen — which extends also to infectious disease — is that new therapies developed with “old school” methods and clinical trials that use all-comers are doomed commercially. Showing an agent in psychiatry or infectious disease is “not inferior to something that costs a quarter a day,” doesn’t serve patients or attract investors. But he sees parallels with oncology, which historically also struggled to show improvements over generics, until “the revolution of precision medicine,” changed the paradigm.

Mammen said that precision approaches that define a mechanistically singular form, for example, of depression, and identify response signatures, can lead to superiority studies that deliver meaningful results and create value. The same is true in infectious disease, where understanding whether the patient will respond to a specific treatment will require tailored approaches.

“In both cases, precision medicine is the answer. It’s easier said than done to find those mechanistic populations, but that has to be the goal.”

Mammen also talked about the expansion of data science, the role AI and machine learning might play in drug development, and how these technologies can enable better uptake of medicines in community settings, for example by extracting signatures from imaging of pathology slides from tests routinely run in medical practices. He also outlined his views on the transition as a leader from pharma to a small biotech, and the different perspectives that each setting brings to the CEO role.