Conference Update June 7, 2017 ASCO 2017 Detailed Presentation Notes Day 5 As part of our ongoing coverage of the 2017 American Society of Clinical Oncology (ASCO) conference, we attended multiple oral presentations on Tuesday June 6 th, and our notes are below. This is our final note for this series. Affected companies include Agios Pharmaceuticals (NasdaqGS: AGIO), Celgene (NasdaqGS: CELG), SFJ Pharmaceuticals (private), Astellas (TYO: 4503), Pfizer (NYSE: PFE), AstraZeneca (NYSE: AZN), Roche (VTX: ROG.VX), and Chugai Pharmaceutical (TYO: 4519). Analysts Sam Slutsky (212) 915-2573 sslutsky@lifescicapital.com Session Notes: Hematologic Malignancies Leukemia, Myelodysplastic Syndromes, and Allotransplant Eytan Stein, MD: Enasidenib in mutant-idh2 relapsed or refractory acute myeloid leukemia (R/R AML): Results of a phase I dose-escalation and expansion study. Companies affected: Celgene, Agios IDH2 mutations occur in about 12% of AML, thereby blocking differentiation. Enasidenib is a potent selective inhibitor of mutant IDH2 and restores differentiation of leukemic cells. This study was designed to interrogate safety and efficacy of enasidenib in patients with mutant IDH2 myeloid malignancies. Best OS by response. 19.7 mos in CRs; 13.6 mos Non-CR; 7 mos No response. Takes time for the responses to come about. Several cycles of therapy are required. Baseline 2HG have similar numbers between the responder and non-responder. Small number of patients went on to transplant. Investigators published a paper describing their finding the journal Blood. Ongoing studies with enasidenib include the Phase III IDHentity trial evaluating enasidenib therapy vs. standard of care regimens in late-stage AML patients, and a Phase I/II studies of enasidenib combination therapies in newly diagnosed AML patients. For analyst certification and disclosures please see page 5 Page 1
Jeffrey E. Lancet, MD: Impact of Targeting Mutations in Myeloid Malignancies Companies affected: Celgene, Agios, Astellas TCGA data suggests 250 recurrent mutations in AML, which comes down to about five mutations per patient. Most common FLT3, NPM1, DNMT3, IDH2 and 1. Optimal targeted therapy in AML: Targeting the driver Targeting initiating or founder mutation Achieving a deep response Amenable to combination with other agents Can prevent resistance conferring mutations The presenter demonstrated enthusiasm for enasidenib as a single agent and potential for combination. Asked whether the lack of a control arm in the enasidenib study hamper development, because ultimately would like to see these patients live longer. Presenter highlighted the results from the CHRYSALIS study with gilteritinib, a FLT3i for treatment of relapsed refractory FLT34 mutant AML. The trial reported impressive response rates as a single agent. One of the highlights from this study is that it used next generation sequencing to quantify a FLT3 mutational burden ratio to characterize a molecular response. In the 80 patient study about a quarter of patients treated with gilteritinib achieved a molecular response. Importantly, in patients that reached a molecular response using this criterion, the median survival was over a year; approximately double that of those who failed to reach a molecular response. These data are the first to show the importance of being able to monitor the response rate level and how it predicts for survival. Session Notes: Lung Cancer Non-Small Cell Metastatic Alice Tsang Shaw, MD, PhD: Efficacy and safety of lorlatinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) with one or more prior ALK tyrosine kinase inhibitor (TKI): A phase I/II study. Company affected: Pfizer Secondary mutations in the ALK domain can introduce resistance to first and second generation TKIs. Lorlatinib is a selective inhibitor against ALK and ROS1 with potency against ALK resistance mutations, including G1202R. In a phase I study showed activity across the blood brain barrier with clinically meaningful results. Study consisted of 6 cohorts consisting of patients with that had undergone prior ALK therapy. Total 82 patients. Primary endpoint was ORR/intracranial ORR. Secondary endpoint: safety and tolerability Results including all cohorts. 1 CR; 26 PR; 27 SD; 17 PD. In patients with prior two prior TKIs. 1 CR; 10 PR; 18 SD; 9 PD. Notable durable responses in patients with one or more ALK TKI therapy of up to 300 days. ORR for patients that received prior ALK TKI therapy with confirmed intracranial lesions. 7 CR; 11 PR; 11 SD; 4 PD. ORR of 18%. Duration of response of up to 7 mos. for patients with intracranial lesions. Most common AE was hyperlipidemia Page 2
Ongoing Phase III Crown study comparing loralatinib to crizotininb in the first-line treatment of patients with ALK+ NSCLC and has begun enrolling patients. Tony Mok, MD, FASCO: Dacomitinib versus gefitinib for the first-line treatment of advanced EGFR mutation positive nonsmall cell lung cancer (ARCHER 1050): A randomized, open-label phase III trial. Companies affected: Pfizer, SFJ Pharmaceuticals, AztraZeneca Dacomitinib is a second generation irreversible EGFRi. Single arm Phase II study of dacomitinib as first line treatment in a subgroup of patients with EGFR activating mutations. RR 76.6%. mpfs 18.2 Phase III ARCHER designed to evaluate dacomitinib vs. gefitinib as first line treatment for pts with advanced NSCLC harboring activating EGFR mutations. Primary endpoint was PFS by blinded independent review and secondary endpoint was investigator assessed PFS, ORR. Study had high Asian population, most non-smokers. Results from ARCHER. In the ITT, PFS was 14.7 mos. in dacomitinib vs. 9.2 mos in gefitinib. Best overall response in blinded independent review was 74% dacomintinib vs. 71.6% in the gefitinib arm. Median duration of the response 14.8 mos. vs. 8.3 mos. OS was not mature, only 36.9% of the events at the time of data cut-off. Change in tumor volume was better in the dacomitinib arm compared to the gefitinib arm. Dacomitinib showed higher toxicity. Diarrhea and dermatitis Overall SAEs were similar between dacomitinib and gefitinib. However, TRSAEs were higher in the dacomitinib arm compared to gefitinib as well as discontinuation rates. AEs were similar to that seen in other studies with dacomitinib. Have reduced dose to manage toxicity. Dacomitinib would be another treatment. There are already three existing therapies. Alice Tsang Shaw, MD, PhD: Alectinib versus crizotinib in treatment-naive advanced ALK-positive non-small cell lung cancer (NSCLC): Primary results of the global phase III ALEX study. Companies affected: Roche, Chugai Pharmaceuticals, Pfizer ALK rearrangements define subset of NSCLC. SOC for patients with ALK rearrangement is crizotinib with an ORR of 74% and mpfs of 10.9 mos. Pts on crizotinib often experience progression after a year of treatment, specifically in the CNS. Previous data showing alectinib treatment results in a 94% ORR and mpfs not reached, 3 year PFS of 62%. Previous studies have shown potent effects of alectinib in CNS lesions, as result its used as standard treatment for ALK positive pts that have progressed on crizotinib. Tested whether alectininb would have superior efficacy over crizotinib as first line therapy for advanced ALK positive NSCLC. (ALEX Study). 303 patients were randomized in the study. Primary endpoint was PFS and key secondary endpoints were time to CNS progression, ORR and OS. 41% of patients had CNS lesion at baseline. 60% had not received treatment for their CNS metastasis. Significantly improved PFS in alectinib group. PFS not reached in the alectinib group (62 PFS events) 11.1 mos. in the crizotinib arm (102 PFS events) Patients with and without CNS mets benefited from alectinib treatment. HR 0.40 in the CNS met group and HR 0.51 in the non- CNS met group. Time to CNS progression at 12 mos. was significantly reduced in the alectinib arm (9.4%) compared the crizotinib arm (41.1%). Page 3
Duration of response was greater in the alectinib arm. Median duration was not reached in alectinib and 11.1 mos. in the crizotinib arm. HR0.36. OS is still immature and not powered to show a difference. Fewer grade 3-5 AEs with alectinib. Common AEs with alectinib were increased bilirubin, myalgia, anemia, and weight gain. A more favorable AE profile than crizotinib. Full study was published in NEJM today. Risk to an Investment Investors should consider the risk of any investment. These stocks can have high risk and high volatility. Clinical stage assets may not be successful in clinical trials or may fail to gain regulatory approval. If products are launched, it is possible that revenues will not meet investor expectations, or that the products will face unexpected competition. The revenues of approved products may also not meet investors expectations, and approval in one disease does not always correlate with success and approval in another disease. Overall market conditions may also affect the value of the underlying securities Page 4
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