Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Fireside Chat: Robert Bradway, CEO, Amgen

• Six therapeutics areas, one is oncology – which area within oncology?
• when partner, acquire?
• Bi-specifics
• oncolytic virus approved the first by FDA
• T Cell therapies
• what is on your wish list?
• Drug Pricing: Assess Value? is the Pricing appropriate yet encourage innovation
• Gov’t funding in Oncology – it is well funding
• Cure?? how far we come

• Amgen has 10% of the oncology drugs market
• multiple myeloma
• hemological oncology
• immuno-oncology
• Signal transduction  – stroma tumors — not our area at present
• innovations is core – 1/2 of molecule are generated internally and 1/5 externally
• active licensing with MD Anderson, CAR-T are is license
• acquisitions in oncology: Oxyn, Bionex, _____
• try only innovation that the biology is believed in
• collaborate vs control
• Copolas – data in Phase III very impressive for multiple myeloma
• insito — Bi-specific approved for hematologic malignancies
• Program in solid tumors internal development
• Six drugs approved – 4 are in oncology
• oncolytic virus – durable improvement for methastatis melanoma – combining it with other oncology PD1, PDL1, checkpoint inhibitor
• ALL – CAR-T may work, T-cell is an important direction
• feel at Present, able to embrace a larger acquisition than early stage like we did three times
• Value equation can prove that revenues can be made in Oncology – Value-based pricing in Healthcare for the society
• Data need be assessed and shared with Payers transparently
• Data Sphere – launced during President GW Bush,
• data set of 30,000 control trial arm, scientists uses SAS interogate the DB from 40 countries — help rethink future study design
• VP Biden – initiative to support dat sharing in oncology
• burden of disease of the elderly
• significant opportunity to invest more
• industry 30 clinical trials in immuno-oncology
• concerned about NIH having enough funds for primarily basis research and less so translational research
• Amgen has 2 immuno-oncology agents – Paradigm shift if the Immune systems will be part of the therapy cycle
• Sequence Cancer genomes
• Geriatric patients treated and do very well – celebrate the accomplishments to Society

Immunotherapy I: Checkpoint Activation and Cancer Vaccines

Among the most promising approaches to activating therapeutic antitumor immunity is the blockade of immune checkpoints. Checkpoint blockade, prevention of inhibitory signaling that limits activation or function of tumor antigen-specific T cells responses, is revolutionizing the treatment of many poor-prognosis malignancies.Panelists explain why this innovative drug class is stirring excitement with its significant long-term cancer remissions—cures, in some cases—and how this unique approach of boosting the body’s own defenses is producing stunning results when combined with standard anticancer therapies and other immunotherapies. They will also detail the experimental vaccines in development that are designed to “wake up” the immune system so it will trigger reliable and effective attacks on cancer cells.

• Capital and energy going into Immune-therapy
• limits of Biomarkers
• Toxicity in checkpoints
• toxicity of PD1
• targeted therapies
• combinatorial stage competing wiht practicality agenda
• Strategy in market is it affecting: Validation and how many drugs are needed
• Pricing and Costs of these drugs – evolution of the economics

• combination will amplify durability of the response
• pipeline and agents – not easy to be sorted out
• melanoma treatment brought hope
• colon cancer, genomic instability emerging
• biological hypothesis at the Patient level
• side effects of immune activation, target cytokines: rashes,
• guidelines on toxicity – limit the therapeutic bone marrow and host
• CAR-T clinically — safety and efficacy – tolerability – barriers to applied therapies
• regulatory agencies sensitive to NOT anticipated toxicities
• why a combination makes sense, small cohort makes sense, diversity Host and Tumor directly – distruction
• CAR-T maintenance of the clone is important to discontinue therapy vs immune response stimulated

• immune of checkpoint blockage – Host response in Cancer – no hits for the therapeutics potentil of the immune system to be applicable for oncology
• Biomarker, mechanism fro tumor immunity, establish principle vs conbinatorial search for candidate
• recognize tumor cells vs health tissue, cell memory – finite period of type for therapy
• homeostatic condition and adoptive immune systems
• vaccines – mechanism tumor antigens – cable to stimulate immune response — HOW DO YOU DO THAT?
• therapeutic dentric cells
• vaccine need ce coupled with other circulatory modulators
• immune therapies and targeted therapies  – overlap of pathways of the response to viral infections replicative capacity with program cell death and memory cells WIRING not yet discovered, modest amount of work in this area.
• Host response and targeted therapies vs checkpoint blockage and toxicity – cynase activations
• Dta 4 doses over few month have positive effect for 10 years

• cancer multifaceted, response is not predictable always
• diverse stages of combination to be effective
• panceratic vs colon – diagnostics and activation are specific
• complex interactions and apthways will lead to immune activations, microenvironment and evolution of tumors, homogenious tumor is a minority, multiple drugs required due to heterogeneity of the tumors
• Outcomes of therapy – Only 2 out of 10 drugs approved will produce income

• immunogenic tumor only 25% response vs resistance
• Ovarian – oncolytic virus study  – we develop a signature for resistance
• understand the tumor and the host
• lysis will enhance immune response by dendritic cells
• result the impulse to see ALL direction in the immune system
• angiogenic vs cytotoxic modulatory
• response criteria vs psuedo response surrogates neede to avail large studies because of the combinatorial factors and specific responses

• Tissue biopsy, rational combination to go forward, avoid access toxicity
• individual tumor, Hutchkins lymphoma – PD1 – biological rational
• design studies for educational value
• diagnostics, define tumor type by cell of origin, colon and lymphoma infiltrate is been assesses shift in diagnosis
• Biomarkers and assays — interpretation of results
• diagnostics as a commercial enterprise
• agents to analyse the samples – premature to see diagnostics bringing homogeneous analysis
• Biopsis are changing and Pathology Labs are not recognized as they used to be, genomics,
• tissue vs serum biomarker
• response criteria redifined – patients pulled out of studies due to response of progression
• Europe – National system pays only for drugs that have proven impact on longevity