Mike: Thanks for joining me today to discuss data-driven CDx development and how the advent of structured multi-modal data can support innovative programs that will ultimately bring more options to patients. To start, can you please share a brief description of your career background?

Over about seven years I built my own lab at Harvard. During that time, I co-founded Merrimack Pharmaceuticals, and in 2008 I moved full-time to Merrimack, leading translational research to drive our lead products through phase 2 clinical development. Ultimately, the U.S. Food and Drug Administration (FDA) approved Merrimack’s drug for pancreatic cancer, ONIVYDE®.

I left Merrimack in 2016 to work in immuno-oncology. I was the chief scientific officer of an antibody company developing T-cell-engaging bispecifics and then, in 2018, I joined TScan Therapeutics as their CSO.

Mike: How do you integrate different modalities of data to inform clinical development programs? What challenges have you faced in doing so?

Genomics-based testing is the most obvious platform to standardize across different companies. If a single assay – such as a genomic sequencing or RNA-seq assay – can provide information on hundreds of biomarkers, we can ease the burden on patients and providers. Using platforms like Tempus’s, providers can perform a single assay to define which currently available drugs are appropriate for a patient’s treatment.

What we’re doing with Tempus is unique because we’re looking for information that’s not currently in the list of readouts you get from next-gen sequencing of a tumor, but something that’s extractable from these standard assays. Tempus is helping us develop a custom pipeline to extract information from standard tests that we need to guide TCR-T therapy development, including loss of heterozygosity at the HLA locus.

Mike: How do you balance the needs of your organization, providers, patients, and others as you navigate the drug development and diagnostic lifecycle?

Most often, biotech companies, particularly early-stage companies, focus first on selecting the right patients. Because biotechs are judged by the success or failure of their first clinical program, it’s important to ensure that every patient who enters a trial has the highest probability of benefiting from the therapy – especially in cases where a lower number of patients are likely to respond.

It’s a balance between moving quickly and getting things right. And it’s in the interest of both the patient and the biotech company to ensure the maximum possible chance of responding in those early-stage trials.

Mike: What is TScan’s companion diagnostic strategy? What has informed your approach and efforts to advance companion diagnostics?

We’ve discovered recently through published RWD studies that there is a significant amount of HLA loss in solid tumors. So, if you don’t test for the presence of the HLA – and many companies don’t – you could risk giving a patient a TCR-T therapy that has no chance of benefiting them. We work with Tempus to develop assays that would test directly for whether the patient’s tumor has undergone HLA loss or not.

Mike: Can you share examples of how you use RWD to inform development?

On the HLA side, we have a myriad of data around HLA prevalence in different patient populations. Understanding the most prevalent HLAs defines which drug development programs we have at TScan and how best to combine them in early-stage trials. The only way to detect HLA loss of heterozygosity is with genomic sequencing; there is no obvious alternative.

Mike: How did you evaluate precision medicine partners and choose a collaborator for your projects?

Mike: What advice do you have for other biopharma companies as they consider a data-driven approach to diagnostic and drug development?

We also need better education around how to develop novel assays in early-stage drug development, and what to expect during the regulatory process for using novel assays in early-stage drug development. For example, people are wary of filing investigational device exemptions (IDEs) for drug development for novel assays while they’re working to file their first investigational new drug (IND) applications with the FDA. In our experience, the FDA often doesn’t require an IDE for a novel assay as many assays, if developed and applied correctly, don’t pose a significant risk to the patient.

There are other elements to the process that they need to know as well – for example, expect fairly long development cycles as you qualify a novel assay prior to starting a clinical trial. Despite the long timelines today, the more routine this process becomes, the more it’ll benefit the industry.

Young companies filing for their first drug are mainly focused on ensuring all steps in the development and regulatory process happen on time. It can seem daunting to layer a novel assay and patient selection strategy onto the process, as well as selecting an appropriate diagnostics partner. But if you don’t do it, you’re doing a disservice to patients and to your drug, which won’t look as compelling to regulators if the studies include patients with no chance of benefiting from the product.

Mike: What else should pharma companies consider as they navigate drug and diagnostic development?

The industry needs to get used to mandating pretreatment biopsies in a phase 1 protocol. We’re trending in this direction; physicians are more willing to ask for a biopsy for their patient because there are a lot of targeted therapies they can suggest based on the results of genomic assays. Getting the appropriate sample is key, because tumor biology changes over time. Biomarkers that may have been present ten years ago may not be relevant for the patient today. It’s important to think ahead, plan early, and prepare to give yourself options.