Ym bio sciences corppres ash2012 dec 10 12

1 YM Corporate Presentation | ASH 2012

Corporate Presentation

ASH 2012


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.


– 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

CYT387: A Potent, Selective JAK1/JAK2 Inhibitor


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


Anemia Impacts Survival in Myelofibrosis

– ~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

Anemia at any time Anemia at diagnosis


CYT387: Target Product Profile

CYT387 is able to provide myelofibrosis

patients with clinically meaningful benefits:

1. Converting

transfusion

dependent

patients to

transfusion

independence

2. Reducing spleen

volume in

patients with

enlarged

spleens

3. Improving

constitutional

symptoms and

quality of life


Safety and Efficacy of CYT387

Phase I/II Data – ASH 2012


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.


9 months of dosing in Core Study

Dosing complete

100 mg QD (n=3)

150 mg QD (n=52)

200 mg QD (n=3)

300 mg QD (n=60)

400 mg QD (n=6)

A Phase I/II Open-Label, Non-Randomized, Dose-Escalation Study

DLT level: 400 mg QD

MTD: 300 mg QD

Continued long term dosing

Dosing ongoing

73 patients (61%) remain in the

Extension Study

Data collection and analysis

ongoing

Core

Study

(n=166)

Extension

Study

(n=120)

150 mg BID (n=42) *

*

*

*Dose level targeted for dose expansion


• 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

Key Entry Criteria


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

Key Clinical Endpoints


Characteristic Value

Number of Subjects 166

Age (years)

Median

Range

68

34-89

Sex

Male

Female

58%

42%

Myelofibrosis

Primary

Post-polycythemia vera

Post-essential thrombocythemia

63%

22%

15%

JAK2V617F Positive 77%

DIPSS-Plus Category*

Int-1

Int-2

High

10%

62%

28%

Subject Baseline Characteristics

Characteristic Value

Prior Therapy

JAK2 inhibitor (ruxolitinib, TG101348, unspecified)

IMiDs (pomalidomide, thalidomide, lenalidomide)

13%

9%

Palpable Splenomegaly > 10cm 79%

Spleen Size (cm) (Spleen Evaluable; n=145)

Mean (STD)

Median

18.3 (6.4)

18.0

RBC Transfusion Dependent (Evaluable; n=68) 44%

Median Hemoglobin (g/dL)

All subjects (n=166)

Transfusion independent subjects (n=93)

Transfusion dependent subjects (n=73)

9.4

10.3

8.7

Platelet Count (109/L)

Median

182

* Based on available data; includes unfavorable karyotype, platelet count and

transfusion dependent status as additional prognostic factors.


• 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

Subject Disposition


Response by Dose (Core Study) 150 mg QD

(n=52)

300 mg QD

(n=60)

150 mg BID

(n=42)

Total1

(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%

Transfusion Independence Response

• 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

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

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


Maximum Duration of Transfusion-Free Period (responders with onset in Core Study; n=46)

*ongoing †data collection ongoing

*

*

*

* *

* *

* *

* *

* *

* *

* *

* *

*

0 100 200 300 400 500 600 700 800 900 1000

Days

Core

Extension†

≥ 6 months: 74%

≥ 12 months: 50%

≥ 18 months: 28%

≥ 24 months: 9%

18

mo

nth

s

12

mo

nth

s

6 m

on

ths

24 m

onth

s

30

mo

nth

s


Percentage of Patients Receiving RBC Transfusions in Prior 4 Weeks

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

0 4 8 12 16 20 24 28 32 36 40

% P

ati

en

ts w

ith

Tra

ns

fusio

ns

Weeks Post Day 1

Week 0: 166 patients

Week 40: 125 patients


Response by Dose (Core Study) 150 mg QD

(n=52)

300 mg QD

(n=60)

150 mg BID

(n=42)

Total1

(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%

Spleen Response

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

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*

• 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


Maximal Change in Palpable Spleen Size (Core Study; n=145)

-100%

-75%

-50%

-25%

0%

25%

50%

75%

% C

han

ge f

rom

Baselin

e

≥25% decrease from baseline: 87%



100% decrease from baseline: 17%


Constitutional Symptoms Response

21% 24% 26% 18%

57% 52%

33%

29%

100%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Night Sweats(n=62)

Pruritis(n=46)

Bone Pain(n=43)

Cough(n=28)

Fever(n=10)

% o

f P

ati

en

ts

Complete Resolution

Marked Improvement


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

Baseline platelets > 150 x 109/L (n=97)

14%

18%

8%

1%

17%

9%

7%

1%

Related Hematologic Adverse Events

*Events occurring in more than one subject

At least possibly related to study drug

Common Terminology Criteria for Adverse Events v3.0


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%

Related Non-Hematologic Adverse Events

1 Includes First Dose Effect




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%

Related Non-Hematologic Laboratory Adverse Events




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

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

CYT387 Conclusions


• 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

Acknowledgements


CYT387 Next Steps


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 Well Suited for Myelofibrosis

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


CYT387 BID Dose Escalation Study

– Designed to explore BID schedule to complement

QD MTD (Starting at 200mg BID, increasing by

50mg BID)

– Spleen response measured by palpation and MRI

– Constitutional symptoms assessed using the

Myelofibrosis Symptom Assessment Form

(MFSAF)

– To assess anemia response, a minimum three

months of transfusion history will be collected

– Comprehensive blood work and biomarkers being

recorded for correlative/mechanistic studies

Mayo Clinic

(Arizona)

MD

Anderson

(Texas)

Huntsman

Cancer Institute

(Utah)

Princess

Margaret

(Ontario)

Jewish

General

(Quebec)

Mayo

Clinic

(Florida)

– Enrolment of 61

patients completed

Q3 2012

– Median follow-up

(range): 5.3 months

(0.5 – 13.9)


Preliminary Efficacy

* Ongoing

MRI Spleen Response

Response by Visit C3D29

Spleen evaluable (n) 53

Spleen response* (≥35% decrease from baseline) 57%

Median spleen decrease -47%

Insert Palpation Data??

Palpation Spleen Response

Spleen Response C3D29

Spleen evaluable (n) 47

Spleen response* 60%


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


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