Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Combination Cancer Therapies: Drug Resistance and Therapeutic Index

Game-changing modern cancer therapies—immunotherapies and targeted therapies, among others—are providing promising treatment outcomes. While the results have been compelling, monotherapy does not meet the needs of many patients who require alternative strategies to achieve optimal therapeutic benefit. Panel experts will describe how combining these therapies with other drugs will steer the field in a direction that promises even better outcomes.

• Optimism
• what drives
• sequencing tissue of tumor
• resistence in combination therapy
• regulatory
• IO very rapid advancement
• price drugs

• 36 yrs at Dana Farber, – Multiple Myeloma specialty – 16 drugs approved last year alone 7 more drugs approved
• genetics of tumor
• no one class of agents:
• immune therapies: vaccines and other immune to achieve memory immune response deals wiht all the mechanisms bringing relapse
• Genetics have evolution, confirm a phenotype, in Myelome – excess protein production DNA damage
• replicative stress, genetic and phenotyp e block replicative RAS
• targeting the biology
• preclinical and their utility for therapy in IO
• models predictive  -success failure is as useful as predictive expected efficacy to be achieved
• combination therapy: immune events in Host to be follow and precursor conditions –
• sequential monitoring
• Moonshot — need for a NATIONAL DB of unifying DATA from blood cancers and solid tumors need be combined
• surrogate marker that can predict
• Praise FDA proactive for breakthrough
• new noval trial design – CMS, NIH, Academia, — small trials with surrogate end points – novel combination
• How to use a surrugate target endpoints – how clinician will used that in the clinic
• priming with combination of [radiation + checkpoints] in use – local tumor and distant in methastesis impact

• thorasic oncology
• combination – as targeted therapy
• lung cancer – no cure, how resistence occure combinations kill resistance clones
• 5 drugs at once for therapeutic index
• combination effective BRAF alone in addition with another drug – efficacy – Protocol
• target therapy with immune -oncologu KRAS with Checkpoint blockage
• resistance of single agent known not known in combination
• Cancer – remission – therapy again – who it evolved – research need to include biopsy alla along: Pre-treatment vs in treatment — NOT enough
• therapy can induce inflammation what is measured is nor immuno – biomarkers, immuno-immuno
• non invasive approches, new therapies

David Schenkein, MD, CEO, Agios Pharmaceuticals, exHead Oncology at Genentech

• ex-Lymphoma DOc
• combination in ClinicalTrial.gov — is not alway scientific
• disappointing – companion diagnostics for a pre specified population
• Science is hard – what id the predictive marker – hard to find predictive markers
• match molecules with right parient — only then take to marker
• relapse – how to bypass Standard of Care – adjuvant setting
• FDA allows novel-novel– is it a synthetic combination
• find surrogates – novel surrogates

• disappointment, incrementally will bring cure
• in IO – setting Standard of care can block innovation because a newly approve will must be include in therapy
• targeted therapy, conceptual GENOMICS structure: like EFGR – preclinical studies to move forword
• RAS
• Preclinical translational model do not work so well
• scale translational preclinically, develop combinations and get approval
• trial of multiple combination in an experimental fashion
• Pharma needs to generate combination the FDA will approve
• early novel-novel combination wihtout knowing the toxicology
• spacing dosing makes differences
• molecular response was not known as predictor, retroactively, become known40% needs 20 patients – early signals

Fireside Chat: Joseph Jimenez, CEO, Novartis

Moderator: Gregg Meyer, MD Chief Clinical Officer, Partners HealthCare

• How Novartis stay focus??
• Drug pricing
• Cost of Healthcare
• developing markets
• Integration of Diagnostics
• Thanks to NOVARTIS for contributions to Cambridge, MA
• Management of Chronic illness
• Athletic Team vs CEO

• early 2000 – Gleevec
• FIVE Types: lung, breast, renal, hematologic cancers,
• immune-oncology 2nd generations – 5 agents – in 5 years next generation IO in a 20 year play
• agents in the pipeline: CML + Gleevac, anti CDK4,
• CAR-T was early –
• 10 year to 15 year play – we added
  William Sellers, MD, Vice President and Global Head of Oncology, Novartis Institutes for BioMedical Research, ex-Broad, ex-Dana Farber
• R&D BioSciences — Cambridge and Basel – Pipeline must be full
• drug pricing: 10% of HealthCare costs – shift from transactional to OUTCOME approach
• we started with Payers – change toVALUE vs Standard of Care
• Clinical benefit, quality of life, lower cost to the Providers, less Physician visit more self administration, help to the SOciety
• shift pricing medicine toward Value to Patients and Society
• Data needed on outcome base price + rebate — to reduce hopitalization in a Cardiovascular drug
• Novartis will be paid on OUTCOME
• Sustainability of HealthCare: adding a billion of new population of young age in the World
• Save 25%-30% in cost of HealthCare if Outcomes of no efficacy will be eliminated
• Emerging markets, out of pocket expense in light no insurance in
• Novartis Access for $1 a month per person – bringing 8 drugs to the developed World
• Oncology Group – use companion diagnosis, other drug are coming to market with a companion diagnostics
• Biologics – Manufacturing – 4 Global plants, last year one was built in Singapore — capacity problem resolved for psorasis drug and other three now manufacture in Singapore
• Positive Patient Outcome: Digital IT Projects
• FDA – Patty Hamburg, brought therapies to patients by changes in FDA
• PKCS2 – Breackthrough therapy designation by FDA
• CAR-T – first with UPenn, site in NJ – Pediatrics – ALL – replication in Vivo cells engineered in the Lab
• Quality assurance built into the process – set the Standard – everyone will follow
• Chronic to survival
• Gleevac – brought normality to life of Patients – 12 – 20 years of survival
• CRISPR technology Intellia, gene Editing – genetic disease
• 2nd generation IO agents
• CAR – T
• over 15 years R&D in Cambridge, MA Basel, SHanghai
• Patents — Gleevac – Transform Cancer exclusivity went generic in US for 100 years CML patients for $1 a day – biggest drug, no more Patent ptotection
• Continium  – incentives for innovation
• Science based – LARGEST Pharma in the world: Motivate, Resources,

Cancer Diagnostics: New Uses, New Reimbursements?

Advances in genetics, genomics and proteomics are driving advances in identifying and treating disease, developing new therapeutics and improving health. Use of genetic testing and molecular diagnostics is rapidly expanding in clinical practice, creating a new, personalized approach to medicine. Panelists describe key new technologies and how they will be integrated into the delivery of care.

• Pathway to bring new discoveries to Patients
• implementation barriers — how aproacing them
• Genomics and the workflow of Care and treatment — guidelines are outdated, Clinicial busy schedule
• Personalized Medicine at ODD with current reimbursement

• hurdle upfront, liquid biopsy
• Payers and Clinicians need to converge
• Genomics altertions several in one Patient – technology is needed for resistance genes to be used
• challenge incorporation of DSS – how use genomics and diagnostics one step removed from therapeutics – paradigm shifts
• Precision Therapeutics (done best) vs Precision Diagnostics (evolving)
• Panel sequencing in tissue – show utility
• monitor disease, biomarker, data analytics

• Regulatory
• scale 10,000 complex Labs
• Test changes – iterative process
• challenges is access – acceptance that diagnostics is not therapeutics
• Silos: Manufacturing, institution, within institution, EMR
• cooperative – X5 growth in volume – value of diagnostics is a contribution to care
• Cardioniopay — 2006 – 17 genes in 2016 70 genes are implicated
• Cancer is a rare disorders
• Regulation for the sake
• Physician criteria vs MedicCare, Insurance, Premium does not cover testing Genomics
• self insured are subsidizing al the tests done and not paid for
• Drive cost down, clinical collrelations on phynotypes

• Companion diagnostics
• Genetic Testing – demand in Cancer – no FDA approved and No reimbursement for the diagnostics
• Uncertainty of FDA fro approval
• guidelines in Molecular classification of tumot=rs for treatment of tumors
• Test for RAS1 Kit has no diagnostics
• Panel testing Utility need be shown gto genomics
• data analytics

• Lung Cancer Geno typing 17000 sequens whole Genome
• Therapeutics and Diagnostics
• what is the new innovation:
• 1. Regulatory – CMS does not have regulatory for Laboratory work
• 2. reimbursement
• 3. implementation deployment
• 4. assess success for a diagnostics
• Barriers to implementation: at Partners vs the rest of the Country
• CONFLICT BETWEEN EVIDENCE-BASED MEDICINE AND PRECISION MEDICINE
• REIMBURSEMENT – based on clinical trials and approvals for treatment
• Insurance does not cover EGRF even though FDA approved drugs are available for 10 years
• detection

• application NGS in Oncology
• world class diagnostics and sequencins molecular diagnostics, develop DSS
• are the standard  high
• innovations in Diagnostics – FDA will be moving for a resseanable solution
• Foundtion One – Genomic testing for Solid Tumors – alteration targeted to clinical target of available drug for OFF Label usage
• reimbursement
• access clinical trial difficult outside Big Centers
• COnnections to community requires DSS IT for implementation
• diagnostics is one step behind for therapeutics — if
• seamless subtyping – subclassification – share information, for-profit need to share with Academis
• gene-fusion solid tumor, sharing needed for Precision Medicine
• different approach – EGFR – reseaonable done with 20% false negative
• 4 out 1000 has the mutation – sharing informations needed
• Molecular diagnostics vs Therapeutics – No Payer will reimburse for testing which using Molecular diagnostics
• integrate clinical from all innovations represented by the Panel technologies

 

• molecular and sequencing
• CLIA
• Genomics Testing and CLIA
• Integrated data from sources available now

New Philanthropy: Patients Driving Innovation

Philanthropy’s role in driving improved cancer care has evolved rapidly over the last decade. Disease foundations have become active in nearly every phase of the care spectrum supporting innovations in the lab, clinic, patient engagement, and regulatory approval among others. Senior philanthropic leaders will describe how the foundation community is redefining roles and finding new ways to help patients as they seek to drive breakthroughs in understanding and care.

Introduction by Scott Sperling, Co-President, Thomas H. Lee, Partners

• Funding Research

• Govrntment funding $5Billion not enough
• Goals for the Foundation – support research and find cure
• ALS Buckett concept

• discover therapies
• cure since 1994 – deploy $1Billion for research of blood cancers
• access
• average donation $75 achieve $300Millions
• Program to train athletes 20 years ago – reach beyond the core constituiencies
• social media active
• funding 300 Projects – 1000 applications a years are accepted, Peer review
• 2008 – Small Biotech – provide non-delutive funds to fund concepts
• Clinical Trial matching  – accelerate the rate of going through the
• UPenn Project was funded $20Million – Novatris Partnered on CAR-T
• Scientific Board – 10 MDs
• FDA – meeting with 14 Patients -dialog with Patients – preferences in therapy – Dr. Pazdor, FDA – give voice to Patients

• Breast cancer cause – Race for Cure – 150 Races per year — come back to the cause
• 103 areas in US 30 regions in the World
• $800Millions for research
• $1.2Billion – for Community Programs
• Areas for BRCA:
• 1. reduce disparity in community of color – Health Equity Initiative
• 2. metastatic disease Initiative
• 3. Young investigators – 50% of funds Young Cancer Researchers – funds dried out
• Survivors $200Million for Immuno-Therapy vs Shawn Parker Fund
• We can’t ignore investment in basic science – diversifying the portfolio
• 100 advocate trained in Science – give presentations in the C0mmunity
• Advocate on Capital Hill on Patients ans Treatment

• Raise money for Dana Farber since 1980 — Money is given to Dana Farber they decide what to do
• PMC – 1/4 million donors – $46 Million donations to Dana Farber annually – alumni event of bike riders
• initiative is replicated in Cleveland, Seattle and other communities
• Kids ride, alumni Parents wanted kids to know, families
• PMC weekend – age 15 – endorsement
• Open ceremonies on TV
• Tracking data of Cancer survivors
• Yakey Building built with input from Patients