PanelParticipantsKey TakeawaysThe New Paradigm and Challenges of CDx Development into the Commercial and Community Setting

• Julie Ramage - national accounts director, dx at Pfizer
• Robert Dumanois, Manager, Reimbursement Strategy, TMO

FDA approval for OncomineDx cost Thermo tens of millions of dollars; yet, approval was just the start down a long pathway with lots of challenges:

• Significant analytical and clinical validation efforts including 200K+ pages submitted, 30K+ samples sequenced, 3 GMP sites inspected, 3 clinical validity studies
• NGS CDx validation takes a ton of work, but hopefully have reduced the timeframe for future tests which will more likely be evaluated upon clinical utility data (as opposed to AV/CV)
• 85% of testing is done in community, 15% is done in AMC; don’t go to AMC if you want to get majority of patients
• AMCs will run large panels (e.g., 500+ genes) for clinical trials
• SoC is still very much: fast TAT, easy reporting and interpretation, physician does NOT want to be liable
• FDA approval doesn’t mean anything if no one is going to pay for the test!

Key learnings:

• The lab business is rough!
• See things from other perspectives and deliver messages in a format that the audience is amenable to
• Recognize that diagnostics is moving from placing platforms to support and integration

Evolution of the Commercial CDx Landscape: A Broad CDx Case Study

• John Truesdell - Commercial Lead for Tissue Testing, Sr. Director, F1CDx

How to bring a broad CDx to market:

• Received approval for F1CDx in Nov. 2017; indicated for use in all solid tumors
• Available commercially in the U.S.
• Available Q4 2018 across the globe
• Also done in central lab, ensures quality across entire system, sites across the globe to enable a central lab model

Some statistics:

• Out of the 100 metastatic cancer patients in the U.S. (not including hematological malignancies), 26 get single-marker testing, 12 get NGS testing, 62 get no molecular testing today
• FMI has reported genomic profiling results to physicians for over 200,0000 patients (as of Q1 2018) with physician orders from over 72 countries
• Collaboration w/ WuXi in China for clinical trials, Dian in Hangzhou China
• Lab in Penzberg, Germany

Large panels present opportunity for incidental findings, as most doctors are not going to roll dice on a 1% prevalent biomarker, they have to find it by accident in many cases.F1CDx required significant collaborative efforts between FMI and pharma: biomarker messaging (education related to biomarker, received and understood by market place), customer biomarker support (being able to triage across different organizations so it doesn’t exist in siloes).CGP is the wave of the future, though at the end of the day, labs must provide customers with the easy button (community setting) for those who cannot keep up with the science, find a product that is reimbursed with all options for patients.LunaDNADawn Berry - CEOLuna DNA is the first genomic and medical research database owned by its research community. Studies have traditionally focused on white males as research subjects; yet now we are at a moment where individuals wish to share in the value created from our data. 17M have experienced DTC products. Consumer directed, population health programs and the portals bring EMRs in, popularity of economics of sharing - individuals recognize that their data has value.BroadOak/DeciBio Think Tank

• Bruce Quinn
• David Cavanaugh
• Bill Snider
• Stephane Budel
• Allison Ballmer
• Ken Carter
• Jim (Rockland Antibody/Assay)
• Chad (lifesciences investor)
• Amanda Murphy (William Blair, sell-side)
• Karl (CSO @ Rockland)
• Claudia (AkronBiotech, CAR-T component manufacturing)
• Stephane Mouradian (New Leaf Venture)
• Mika Wang
• Bart Kus (MedImmune spin-out Viela Bio)
• Michael (BroadOak)

Just scratching the surface for I/O, though challenges remain:

• Technical challenges:
• Lots of cell therapy products that may work with specific populations, but still a need for population / therapy matching
• Expression at DNA, RNA or protein level? Which matters most?
• Limitation in using one’s own T-Cells for therapy
• Antigen delivery remains a challenge (i.e., antigen delivery systems that optimize antigen presentation and induce protective immune responses; several cancer vaccine trials have failed due to lack of effective antigen delivery system)
• TAT is too long (currently ~3.5 months for neoantigen sequencing?)
• Market access challenges: Reimbursement gating adoption (in certain markets - China is pushing ahead in CAR-T with over 200 companies)

Investors are still wary of liquid biopsy frenzy, anticipating a market shake up similar to NIPT that leaves a few, dominant players

• PLA code (PAMA rule, assay specific) allows companies to differentiate, providing a competitive advantage (deviates from NIPT story, may indicate LBx less susceptible to pricing erosion?)
• ExosomeDx likely overvalued, given lofty goals of $20-$30mm revenues in ~5 years
• However, exosomes may be a right delivery system with ability to overcome some of the challenges with CAR-T therapies (i.e., antigen delivery system)
• Find a specific niche/use case first (e.g., Grail with nasopharyngeal carcinoma, prove utility; Grail conspiracy theory)
• Despite NCD, many labs not pursuing FDA approval (William Blair NGS Survey 2018) ~67% of labs surveyed either do not plan to pursue FDA regulatory / approval clearance or are unsure. Only ~7% of labs plan to invest in FDA regulatory processes and only 2 over $5M Makes sense given TMO spent tens of millions pursuing FDA approval for Oncomine Dx, who has appetite / deep enough pockets for that

Despite challenges with LBx, undervalued opportunities exist:

• OEM companies e.g., antibody producers for CAR-T (“make the tools and picks”)
• Innovative dx models that can happen through established legacy channels (e.g., liquid biopsies through dialysis centers, saliva-based liquid biopsy through dentists driving decentralization
• DTC (e.g., saliva-based LBx, Theranos resurrected, Nova Bio)
• CTC (in ~3 years as sensitivity of single cell seq technology improves)

Centralization / decentralization of testing:

• Labs expect to insource more testing from reference lab (pointing to decentralization); few expect to outsource more test volume to reference lab (William Blair NGS Survey)
• Imaging dx will likely decentralize

Other:

• Non-traditional players (e.g., Seqster) integrating EMR/EHR data with genomic and imaging data
• Radiology (DC)
• Non-oncology liquid biopsy (e.g., autoimmune disease, neurobiology)
• Methylation / epigenetics, trial readouts to come

Clinico Genomics: What is it and Why do We need it?

• Ken Carson - Flatiron Health, Senior Medical Director
• Wendy Rubinstein, Cancer LinQ, ASCO

• Flatiron limited to U.S. for now (vernacular used in charts needs to be anglo, if in different languages would need to work with boots on the ground to really understand that).
• Cancer LinQs' 5 year goal - internationalization.
• On patient informed consent & monetizing data: there are companies and startups out there trying to play into that sentiment; the market will tell whether they think that’s what is going on.

Accelerating the Path to Coverage: NGS Testing in Lung Cancer

• Robert Dumanois, Manager, Reimbursement Strategy at Thermo Fisher

• Adoption of OncomineDx in the community setting is growing rapidly; ⅔ of lung patients are 65+ years of age and Medicare covers 60M lives; commercial / private payers covers 120M+ lives

Precision Dx in Light of the Recent NCD (Palmetto MolDx Medical Director)

• Jim Almas, Medical Director, MolDX, Palmetto GBA

• Still a lot to be worked out after NCD, several outstanding questions to be answered e.g., is AML considered an “advanced” cancer (to be reimbursed by NCD) - these will be worked out 303 days from 3/16/18
• For a new test similar to F1CDx, clinical utility (whether it changes care/patient outcomes) will be most important to look at since AV/CV already well established across platforms (issues can be easily fixed); must show new ADLT / CDLT is not inferior to existing CDx in the setting of device for that specific indication
• Still inconsistencies in what is covered, what MACs cover (e.g., Novitas v. MolDx) - more collaborations happening than ever before to overcome these inconsistencies
• Look at latest PIM (online) for guidance re: LCD

Aligning Coding and Evidence Pathways to secure Coverage in the Age of PLA Coding

• Shivang Doshi, Director, Boston Healthcare Associates

• Getting a PLA code is not difficult, it’s really about aligning the timing with clinical evidence that your assay/test performs and has utility (if no clinical utility evidence, then no point in applying for a PLA code)
• First regulatory approval, then apply for and establish a PLA code then set reimb.
• Payment set via PAMA, interim reimbursement is a viable pathway for sole-sourced test providers