CYT387 is a JAK1/JAK2 inhibitor being studied for the treatment of myelofibrosis. A phase I/II study found that CYT387 showed promising efficacy based on three key measures: (1) It converted over 68% of transfusion dependent patients to transfusion independence; (2) It reduced spleen size in over 37% of patients based on IWG-MRT criteria; and (3) It improved constitutional symptoms in the majority of patients. The safety profile was acceptable with the most common adverse events being low grade thrombocytopenia and anemia. The study demonstrated that CYT387 has a favorable risk-benefit profile for the treatment of myelofibrosis.
Mmc1 2 The Lancet - Supplementary appendix 10/15/2014John Redaelli
This appendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem
cell-derived retinal pigment epithelium in patients with age-related macular degeneration
and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet
2014; published online Oct 15. http://dx.doi.org/10.1016/S0140-6736(14)61376-3.
Susan O'Brien, M.D., Professor, Dept. of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center: Newest Strategies in the Treatment of CML/CLL presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center.
BioNIR/EluNIR eDES: 1 Year Outcomes of BIONICS and NIREUS studiesMedinol Ltd
Dr. David Kandzari's overview of the 1 year outcomes of the BIONICS and NIREUS pivotal & randomized studies of the EluNIR elastomer DES by Medinol (formerly BioNIR). Presented during TCT 2016
Mmc1 2 The Lancet - Supplementary appendix 10/15/2014John Redaelli
This appendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem
cell-derived retinal pigment epithelium in patients with age-related macular degeneration
and Stargardt’s macular dystrophy: follow-up of two open-label phase 1/2 studies. Lancet
2014; published online Oct 15. http://dx.doi.org/10.1016/S0140-6736(14)61376-3.
Susan O'Brien, M.D., Professor, Dept. of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center: Newest Strategies in the Treatment of CML/CLL presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center.
BioNIR/EluNIR eDES: 1 Year Outcomes of BIONICS and NIREUS studiesMedinol Ltd
Dr. David Kandzari's overview of the 1 year outcomes of the BIONICS and NIREUS pivotal & randomized studies of the EluNIR elastomer DES by Medinol (formerly BioNIR). Presented during TCT 2016
WASHINGTON, D.C.—Use of certain doses of atopaxar in acute coronary syndrome patients can reduce rates of bleeding, cardiovascular events and better achieve platelet inhibition, according to the results of the LANCELOT-ACS trial presented Sept. 23 as a late-breaking clinical trial during the 2010 Transcatheter Cardiovascular Therapeutics (TCT) annual meeting.
www.cardiovascularbusiness.com/topics/coronary-intervention-surgery/tct-lancelot-acs-says-certain-doses-atopaxar-can-reduce-bleeding-cv-events
From Alzahra Oncology Center in Dubai, in the heart of Middle East lead by Dr Sadir Alrawi AMERICAN boarded, minimal invasive surgery, with Dr Thamir Alkasab, Khaled Koutech and Dr Ziad Aluobiadi
Volker Diehl, M.D., Professor, University of Cologne, Germany Customization: The Treatment of Hodgkin's Disease
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Join expert faculty members Joseph J. Eron, Jr., MD, and Kimberly Y. Smith, MD, MPH, for a review of the HIV highlights of this important annual conference.
WASHINGTON, D.C.—Use of certain doses of atopaxar in acute coronary syndrome patients can reduce rates of bleeding, cardiovascular events and better achieve platelet inhibition, according to the results of the LANCELOT-ACS trial presented Sept. 23 as a late-breaking clinical trial during the 2010 Transcatheter Cardiovascular Therapeutics (TCT) annual meeting.
www.cardiovascularbusiness.com/topics/coronary-intervention-surgery/tct-lancelot-acs-says-certain-doses-atopaxar-can-reduce-bleeding-cv-events
From Alzahra Oncology Center in Dubai, in the heart of Middle East lead by Dr Sadir Alrawi AMERICAN boarded, minimal invasive surgery, with Dr Thamir Alkasab, Khaled Koutech and Dr Ziad Aluobiadi
Volker Diehl, M.D., Professor, University of Cologne, Germany Customization: The Treatment of Hodgkin's Disease
Presented at New Frontiers in the Management of Solid and Liquid Tumors hosted by the John Theurer Cancer Center at Hackensack University Medical Center. jtcancercenter.org/CME
Join expert faculty members Joseph J. Eron, Jr., MD, and Kimberly Y. Smith, MD, MPH, for a review of the HIV highlights of this important annual conference.
Describes the changes made over years in the management of advanced renal cell carcinoma with special focus on re-empowering of the concept of immunotherapy
Pathways and targets how might these affect my treatment decisions gail eckh...Fight Colorectal Cancer
Dr. Gail Eckhardt
Professor and Head of the Division of Medical Oncology at the University of Colorado Denver and Health Sciences Center.
Join us for an exciting webinar about pathways and targets. Dr. Eckhardt will discuss the basic of pathways within a cancer cell, and how (and why) they can affect treatment options for patients. She'll explain how we learn about how new pathways are discovered, and how this information tell us what drugs may work in certain patients and why some drugs don’t.
Dr. Eckhardt will discuss the idea of targeted therapies, and the difference between them and regular chemotherapy. She'll talk about the relationship between pathways and targeted drugs, and how this may impact drug development in the future.
Using Novel Kidney Biomarkers to Guide Drug Therapy.pdfDr.Mahmoud Abbas
Using Novel Kidney Biomarkers to Guide Drug Therapy: Presentation by Dr Sandra Gill , President SCCM at the Egyptian Critical Care Summit 2022 held at Cairo, Egypt and organized by the Egyptian College of Critical care Physicians (ECCCP)
2. Safe Harbor
This presentation may contain forward-looking statements, which reflect the Company's current
expectation regarding future events. These forward-looking statements involve risks and
uncertainties that may cause actual results, events or developments to be materially different
from any future results, events or developments expressed or implied by such forward-looking
statements. Such factors include, but are not limited to, changing market conditions, the
successful and timely completion of clinical studies, the establishment of corporate alliances, the
impact of competitive products and pricing, new product development, uncertainties related to
the regulatory approval process or the ability to obtain drug product in sufficient quantity or at
standards acceptable to health regulatory authorities to complete clinical trials or to meet
commercial demand, and other risks detailed from time to time in the Company's ongoing
quarterly and annual reporting. Except as required by applicable securities laws, we undertake
no obligation to publicly update or revise any forward-looking statements, whether as a result of
new information, future events or otherwise.
2 YM Corporate Presentation | ASH 2012
3. CYT387: A Potent, Selective JAK1/JAK2 Inhibitor
– Highly specific, small molecule, ATP-
competitive, JAK1/JAK2 inhibitor
– Rationally designed for optimal JAK binding
– Inhibits cellular proliferation driven by JAK2
or JAK1, but not JAK3 or other mechanisms
– Inhibits STAT phosphorylation downstream
of constitutively active JAK2 or cytokine-
stimulated JAK1 or JAK2
– Orally active
– Favourable preclinical profile
3 YM Corporate Presentation | ASH 2012
4. Clinical Presentations of Myelofibrosis
– Decreased erythropoiesis or thrombopoiesis
– Proliferation of dysfunctional megakaryocytes
– Hypercellular bone marrow leading to fibrosis
– Extramedullary hematopoiesis
– Elevated cytokine levels
– Anemia – often requiring transfusions
– Thrombocytopenia
– Splenomegaly
– Constitutional symptoms
Fatigue, night sweats, pruritus, bone pain,
weight loss, fever
4 YM Corporate Presentation | ASH 2012
5. Anemia Impacts Survival in Myelofibrosis
Anemia at diagnosis Anemia at any time
– ~70% of myelofibrosis patients are Intermediate-II or High risk †
– Estimated that 30-50% of all myelofibrosis patients are transfusion dependent‡,
majority of whom are Intermediate-II and High risk patients
† DIPSS-Plus; Gangat et al. JCO 2011; 29(4), 392
‡ Elena et al. Haematologica 2011 96(1) 167
5 YM Corporate Presentation | ASH 2012
6. CYT387: Target Product Profile
CYT387 is able to provide myelofibrosis
patients with clinically meaningful benefits:
1. Converting 2. Reducing spleen 3. Improving
transfusion volume in constitutional
dependent patients with symptoms and
patients to enlarged quality of life
transfusion spleens
independence
6 YM Corporate Presentation | ASH 2012
7. Safety and Efficacy of CYT387
Phase I/II Data – ASH 2012
7 YM Corporate Presentation | ASH 2012
8. Phase I/II Study of CYT387, a JAK1/JAK2
Inhibitor for the Treatment of Myelofibrosis
1Mayo Clinic, Rochester, MN
2Stanford University School of Medicine, Stanford, CA
3Princess Margaret Hospital, Toronto, ON
4Royal Melbourne Hospital, Parkville, Australia
5Dana Farber Cancer Institute, Boston, MA
6Jewish General Hospital, Montreal, QC
7YM BioSciences Inc., Mississauga, ON
54th ASH Annual Meeting, December 9, 2012
Animesh Pardanani1, MBBS, PhD; Jason Gotlib2, MD, M.S.; Vikas Gupta3, MBBS, MD, MRCP, FRCPath; Andrew W
Roberts4, MBBS, PhD, FRACP, FRCPA; Martha Wadleigh5, MD; Shireen Sirhan6, MD, FRCP; Jun Kawashima7, MD;
Linda M Bavisotto7, MD; Mark Kowalski7, MD, PhD; and Ayalew Tefferi1, MD.
8 YM Corporate Presentation | ASH 2012
9. A Phase I/II Open-Label, Non-Randomized,
Dose-Escalation Study
Core Extension
Study Study
(n=166) (n=120)
9 months of dosing in Core Study Continued long term dosing
Dosing complete Dosing ongoing
100 mg QD (n=3) 73 patients (61%) remain in the
150 mg QD (n=52) * * Extension Study
150 mg BID (n=42)
200 mg QD (n=3)
300 mg QD (n=60) * Data collection and analysis
400 mg QD (n=6) ongoing
DLT level: 400 mg QD
MTD: 300 mg QD
*Dose level targeted for dose expansion
9 YM Corporate Presentation | ASH 2012
10. Key Entry Criteria
• PMF or post-ET/PV MF as per revised WHO criteria
• High risk or Intermediate-2 risk MF (as defined by the International Prognostic
Scoring System [IPSS]); or
• Intermediate-I risk MF (IPSS) associated with symptomatic
splenomegaly/hepatomegaly and/or unresponsive to available therapy
• Evidence of acceptable organ function within seven days of initiating study drug,
including:
• Absolute neutrophil count ≥ 500/μL
• Platelet count ≥ 50,000/μL
10 YM Corporate Presentation | ASH 2012
11. Key Clinical Endpoints
Clinical Responses:
• Anemia response according to IWG-MRT criteria
• Minimum transfusion-free period of 12 weeks (transfusion dependency by IWG-MRT)
• Minimum 2 g/dL increase in hemoglobin (requires hemoglobin <10 g/dL at baseline)
• Spleen response according to IWG-MRT criteria
• Minimum 50% decrease from baseline in palpable spleen length lasting at least 8 weeks
(for baseline spleens ≥10 cm)
• 100% decrease from baseline in palpable spleen length lasting at least 8 weeks (for
baseline spleens >5 cm and <10 cm)
• Improvement in constitutional symptoms
Safety Assessments:
• MTD determination
• Adverse events
• Laboratory assessments
11 YM Corporate Presentation | ASH 2012
12. Subject Baseline Characteristics
Characteristic Value Characteristic Value
Prior Therapy
Number of Subjects 166 JAK2 inhibitor (ruxolitinib, TG101348, unspecified) 13%
IMiDs (pomalidomide, thalidomide, lenalidomide) 9%
Age (years)
Palpable Splenomegaly > 10cm 79%
Median 68
Range 34-89
Spleen Size (cm) (Spleen Evaluable; n=145)
Sex Mean (STD) 18.3 (6.4)
Male 58% Median 18.0
Female 42%
RBC Transfusion Dependent (Evaluable; n=68) 44%
Myelofibrosis
Primary 63% Median Hemoglobin (g/dL)
Post-polycythemia vera 22% All subjects (n=166) 9.4
Post-essential thrombocythemia 15% Transfusion independent subjects (n=93) 10.3
Transfusion dependent subjects (n=73) 8.7
JAK2V617F Positive 77%
Platelet Count (109/L)
Median 182
DIPSS-Plus Category*
10% * Based on available data; includes unfavorable karyotype, platelet count and
Int-1
62% transfusion dependent status as additional prognostic factors.
Int-2
28%
High
12 YM Corporate Presentation | ASH 2012
13. Subject Disposition
• Median follow-up (range) for Core and Extension: 16.9 months (0.8 – 34.2*)
• Study discontinuation during Core: n=42 (25%); 75% retention rate
• Reasons for discontinuation during Core (n=42)
• Unrelated comorbid conditions (n=14)
• Disease progression (n=8)
• Possibly or probably related adverse events (n=8)
• Neuropathy (n=2) • Cough (n=1)
• Transaminitis (n=1) • Thrombocytopenia (n=1)
• Hepatitis B (n=1) • AST increased (n=1)
• Muscular weakness (n=1)
• Investigator’s decision (n=5)
• Subject withdrew consent (n=4)
• Stem cell transplant (n=2)
• Intercurrent illness (n=1)
• Deaths during Core: n=16 (10%)
*Ongoing as of November 2012
13 YM Corporate Presentation | ASH 2012
14. Transfusion Independence Response
150 mg QD 300 mg QD 150 mg BID Total1
Response by Dose (Core Study)
(n=52) (n=60) (n=42) (n=166)
Transfusion dependent at baseline (evaluable) 24 28 14 68
Transfusion independence rate (12 wks) 63% 75% 57%2 68%
Minimum 2 g/dL increase in hemoglobin level (8 wks) 11% 8% 14% 13%
IWG-MRT anemia response rate 48% 55% 36% 48%
• Of the transfusion dependent patients who did not achieve a full transfusion independence response,
23% achieved at least a 50% reduction in transfusion requirement in any 3-month period
Onset and Durability of Response (Core and Extension Study) Median Min-Max
Time to confirmed response (12 weeks) (Core; days) 3 85 85-353
Duration of transfusion-free period (12 weeks) (Core and Extension; days) 3 Not yet reached 85-988*
• 3 additional subjects achieved 12 week transfusion independence response during the Extension Study
1 Includes 100mg QD (n=3), 200mg QD (n=3), and 400mg QD (n=6) doses
2 Not statistically significant vs. 300mg QD
3 Data based on responders
* Ongoing as of November 2012
14 YM Corporate Presentation | ASH 2012
16. Percentage of Patients Receiving RBC Transfusions
in Prior 4 Weeks
50%
45%
% Patients with Transfusions
40% Week 0: 166 patients
Week 40: 125 patients
35%
30%
25%
20%
15%
10%
5%
0%
0 4 8 12 16 20 24 28 32 36 40
Weeks Post Day 1
16 YM Corporate Presentation | ASH 2012
17. Spleen Response
150 mg QD 300 mg QD 150 mg BID Total1
Response by Dose (Core Study)
(n=52) (n=60) (n=42) (n=166)
Spleen evaluable (n) 47 51 37 145
Spleen response (IWG-MRT) 32% 39% 38% 37%
Median spleen decrease at six months2 -36% -38% -46% -38%
• 3 additional subjects achieved spleen response during the Extension Study
• 11 subjects were evaluable for MRI response at six months (≥ 35% decrease in spleen volume)
• 45% response at six months
• 41% median decrease from baseline at six months
Onset and Durability of Response (Core and Extension Study) Median Min-Max
Time to IWG-MRT response (Core; days) 22 6-260
Duration of response (Core and Extension; days) 744† 56-859*
1 Includes 100 mg QD (n=3), 200 mg QD (n=3), and 400 mg QD (n=6) doses
2 Based on patients with C6D29 spleen assessment reported
* Ongoing as of November 2012
† As of November 2012
17 YM Corporate Presentation | ASH 2012
18. Maximal Change in Palpable Spleen Size
(Core Study; n=145)
75%
≥25% decrease from baseline: 87%
≥50% decrease from baseline: 50%
50% ≥75% decrease from baseline: 25%
100% decrease from baseline: 17%
% Change from Baseline
25%
0%
-25%
-50%
-75%
-100%
18 YM Corporate Presentation | ASH 2012
20. Related Hematologic Adverse Events
Adverse Event *(n=166) Grade 1 Grade 2 Grade 3 Grade 4
Anemia 2% 2% 2% 0%
Leukopenia 2% <1% 0% <1%
Neutropenia <1% 2% 1% 2%
Thrombocytopenia 14% 8% 17% 7%
Baseline platelets > 150 x 109/L (n=97) 18% 1% 9% 1%
*Events occurring in more than one subject
At least possibly related to study drug
Common Terminology Criteria for Adverse Events v3.0
20 YM Corporate Presentation | ASH 2012
21. Related Non-Hematologic Adverse Events
Adverse Event (n=166) Incidence ≥ 10% Grade 1 Grade 2 Grade 3 Grade 4
Diarrhea 18% 4% 0% 0%
Dizziness1 22% 1% 0% 0%
Headache 14% 0% 1% 0%
Nausea 20% <1% 0% 0%
Neuropathy peripheral 25% 2% 0% 0%
At least possibly related to study drug
Common Terminology Criteria for Adverse Events v3.0
1 Includes First Dose Effect
21 YM Corporate Presentation | ASH 2012
22. Related Non-Hematologic Laboratory Adverse Events
Adverse Event (n=166) Incidence ≥ 5% Grade 1 Grade 2 Grade 3 Grade 4
ALP increased 5% 1% 1% 0%
ALT increased 9% 3% 2% 0%
Amylase increased 7% 2% 0% 0%
AST increased 9% 2% 1% 0%
Bilirubin increased 7% 2% 0% 0%
Creatinine increased 5% 3% 0% 0%
Lipase increased 8% <1% 4% 0%
At least possibly related to study drug
Common Terminology Criteria for Adverse Events v3.0
22 YM Corporate Presentation | ASH 2012
23. CYT387 Conclusions
CYT387 treatment results in significant, durable responses in anemia, splenomegaly and
constitutional symptoms in MF patients
– Substantial decrease in percentage of patients requiring transfusions during study (44% at
baseline; <10% at week 40)
– 68% of patients achieved a durable 12-week transfusion independence response rate with a
maximal duration of response approaching 3 years; overall IWG anemia response rate was
48%
– 50% of transfusion independence responders achieved a transfusion-free period lasting ≥ 1
year
– 37% of patients exhibited a durable spleen response per IWG-MRT with a maximal duration
of response of nearly 2.5 years
– Complete resolution or marked improvement of common constitutional symptoms is achieved
in the majority of subjects
23 YM Corporate Presentation | ASH 2012
24. CYT387 Conclusions
• CYT387 is well tolerated in myelofibrosis patients for dosing periods currently up to
three years and ongoing
– Majority of adverse events are Grade 1
– Common reported adverse events include thrombocytopenia; transient, mild dizziness; mild
peripheral neuropathy; and abnormalities in liver/pancreas-related laboratory tests
– Treatment-emergent anemia and neutropenia are rare
• 300mg QD is a safe dosing regimen providing compelling efficacy and has been
selected for use in the Phase III clinical development program
24 YM Corporate Presentation | ASH 2012
25. Acknowledgements
• Animesh Pardanani, Mayo Clinic, Rochester, MN
• Jason Gotlib, Stanford University School of Medicine, Stanford, CA
• Vikas Gupta, Princess Margaret Hospital, Toronto, ON
• Andrew Roberts, Royal Melbourne Hospital, Parkville, Australia
• Martha Wadleigh, Dana Farber Cancer Institute, Boston, MA
• Shireen Sirhan, Jewish General Hospital, Montreal, QC
• Patients and their Families
25 YM Corporate Presentation | ASH 2012
27. CYT387 Well Suited for Myelofibrosis
Variable Diagnosis* >1 year* CYT387
Anemia 38% 64% Benefit
Transfusion dependency 25% 45% Benefit
Palpable spleen >10cm 21% 46% Benefit
Constitutional symptoms 29% 34% Benefit
CYT387 has a profile that addresses MF clinical needs and overarching risk factors
> Benefit on anemia and transfusion dependency
> Activity for spleen and symptoms
> Low myelosuppression
CYT387 is well tolerated for dosing periods up to and exceeding three years
* Mayo Clin Proc 2012;87(1): 25-33
27 YM Corporate Presentation | ASH 2012
28. CYT387 BID Dose Escalation Study
– Designed to explore BID schedule to complement
QD MTD (Starting at 200mg BID, increasing by
50mg BID)
– Enrolment of 61
– Spleen response measured by palpation and MRI
patients completed
– Constitutional symptoms assessed using the Q3 2012
Myelofibrosis Symptom Assessment Form
– Median follow-up
(MFSAF)
(range): 5.3 months
– To assess anemia response, a minimum three (0.5 – 13.9)
months of transfusion history will be collected
– Comprehensive blood work and biomarkers being
recorded for correlative/mechanistic studies
MD Huntsman Princess Jewish Mayo
Mayo Clinic
Anderson Cancer Institute Margaret General Clinic
(Arizona)
(Texas) (Utah) (Ontario) (Quebec) (Florida)
28 YM Corporate Presentation | ASH 2012
30. CYT387: Next Steps
ASH 2012
• Phase I/II Core study results strongly reinforce differentiated profile
Business Development
• Explored multiple opportunities to develop CYT387 with other
companies
• Conducted a broad, robust business development process
• Rationalized portfolio
• Process on-track to conclude in the near-term
Phase III
• Preparations for Phase III advancing under assumption of
collaboration/hand-off
30 YM Corporate Presentation | ASH 2012