This document outlines a proposed clinical trial protocol to evaluate the efficacy and safety of DM-102, an investigational antisense oligonucleotide, for the treatment of type 2 diabetes mellitus. The trial would be a 12-week, randomized, double-blind, placebo-controlled, multi-center phase IIb study. The primary objective is to evaluate the effect of DM-102 on HbA1c levels compared to placebo. Secondary objectives include evaluating effects on body weight, fasting plasma glucose, post-prandial glucose, lipids, insulin secretion, C-peptide, glucagon, and safety parameters. The trial plans to enroll 150 patients on metformin monotherapy or dual therapy randomized to placebo, 25mg DM-

1. Protocol Presentation
Therapeutic Area: Type 2
Diabetes Mellitus
Presenters:
Dr Manjesh P S
Dr Pooja S G
JR-III, Dept. Of Pharmacology & Therapeutics
Seth GSMC & KEMH

2. Flow of Presentation
• Definition
• Problem Statement
• Diagnosis
• Current Treatment Guidelines
• Issues and Unmeet need
• Pathophysiology
• Investigational Product
• Ca β3 and Impaired Insulin
Secretion
09-02-2021 2
• Study title and details
• Objectives and endpoints
• Study Design
• Sample size Calculation
• Inclusion and Exclusion Criteria
• Study timeline, Visit plan
• Drug/Placebo administration
• Rescue & concomitant
medication
• Withdrawal Criteria
• Statistical Analysis

3. Definition of Type 2 Diabetes Mellitus (T2DM)
Type 2 DM is a heterogeneous group of
disorders characterized by
• Variable degrees of insulin resistance
• Impaired insulin secretion
• Increased glucose production.
09-02-2021 3
Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J. Harrison's
principles of internal medicine.19th ed. New York: McGraw-Hill; 2015.

4. Burden of the Disease
• 1 in 2 (212 million) people with
diabetes were undiagnosed1
• The cost of diabetes worldwide
was US$1·31 trillion in 2015 2
1) IDF DIABETES ATLAS, 8th edition, 2017. 2) The Lancet. doi: 10.1016/S2213-8587(17)30097-9.
09-02-2021 4
425 million
(20-79 yrs)
2017
2045
G
l
o
b
a
ll
y
629 million

5. 09-02-2021 5
• Asia is the epicentre of T2DM epidemic1
• Prevalence of Type 2 diabetes in adults : 8.8%2
1. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications.
Nat Rev Endocrinol. 2018 Feb;14(2):88-98
2. IDF Diabetes.

6. Pathophysiology of Type 2 DM
09-02-2021 6
Brunton L, Knollmann B, Hilal-Dandan R. Goodman & Gilman's. New York, N.Y.: McGraw-Hill Education LLC.; 2018.
Environmental & Genetic factors
Insulin resistance
Series of pathogenic mechanisms
Hyperglycemia
Decreased insulin secretion
Increased Glucose production
Defect in fat & protein metabolism

7. Pathophysiology of Type 2 DM
09-02-2021 7
Brunton L, Knollmann B, Hilal-Dandan R. Goodman & Gilman's. New York, N.Y.: McGraw-Hill Education LLC.; 2018.
• Early Beta cell dysfunction

8. Diagnosis of Type 2 DM
• FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least
8 h.*
OR
• 2-h PPG ≥ 200 mg/dL (11.1 mmol/L) during OGTT.
The test should be performed as described by the WHO, using a glucose load
containing the equivalent of 75-g anhydrous glucose dissolved in water.*
OR
• A1C ≥ 6.5% (48 mmol/mol). The test should be performed in a laboratory using a
method that is NGSP certified and standardized to the DCCT assay.*
OR
• In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a
random plasma glucose ≥ 200 mg/dL (11.1 mmol/L).
09-02-2021 8

9. Current Treatment Guidelines
Diabetes Management Algorithm, Endocr Pract. 2019;25(No. 1)
• Lifestyle optimization is essential for all patients with diabetes.
• The choice of diabetes therapies must be individualized based
on:
Initial A1C
Duration of T2D &
Obesity status.
• Comprehensive care: Comorbidities and complications
09-02-2021 9

10. Diabetes Management Algorithm, Endocr Pract. 2019;25(No. 1)
09-02-2021 10
Glycemic Control Algorithm

11. Issues & Unmet Need
• Mimicking the pattern of premonitory insulin secretion is an essential
feature of normal glucose tolerance – key challenge for successful
insulin therapy in diabetic patients.
• Discontinuation of GLP-1Receptor Agonists due to –
➢Inadequate blood glucose control(45.6%)
➢lack of weight loss(25.4%)
➢Gastrointestinal side effects(64.4%)
09-02-2021 11
2. Sikirica M, Martin A, Wood R, Leith A, Piercy J, Higgins V. Reasons for discontinuation of GLP1 receptor agonists: data from a
real-world cross-sectional survey of physicians and their patients with type 2 diabetes. Diabetes, Metabolic Syndrome and
Obesity: Targets and Therapy. 2017;Volume 10:403-412.
1. Brunton L, Knollmann B, Hilal-Dandan R. Goodman & Gilman's. New York, N.Y.: McGraw-Hill Education LLC.; 2018.

12. Issues – Limitations of Current Medications
09-02-2021 12
Sulphonyl urea
• Weight gain
• Hypoglycemia risk
• Hastens beta-cell
dysfunction
Meglitinides
• Hypoglycemia risk
• Weight gain
• Mealtime dosing
DPP-4 inhibitor
• Possible pancreatitis risk
• Modest A1C effect
• Cost
Insulin
• Hypoglycemia
• Weight gain
• Injection site effects
GLP-1 agonist
• Nausea/vomiting
• Injection site effects
• Questionable pancreatitis
or thyroid cancer risk
• Cost
SGLT-2 inhibitors
• Genital mycotic infections
• Urinary tract infections

13. 09-02-2021 13
There is a Need for New Therapeutic Options

14. Investigational product (IP) – DM 102
Traditional Drug Treatment
Antisense oligonucleotide Treatment
Antisense Oligonucleotides (ASO)1
Short synthetic strands of DNA that consist of 15-25 nucleotide
units target their complementary stretches of RNA
09-02-2021 14
1. Dinc E. Antisense Oligodeoxynucleotide Technology: A Novel Tool for
Gene Silencing in Higher Plants. PhD Thesis. University of Szeged; 2012.

15. Caβ3 and Impaired Insulin Secretion
09-02-2021 15
Voltage-gated Ca2+ channels (Cav) play a critical role in Insulin secretion
Pancreatic β cell

16. 09-02-2021 16
expression of Cavβ3 in islets
Improved [Ca2+]i dynamics
↑ First and second phase Insulin
secretion
Antisense Oligonucleotide

17. 09-02-2021 17
Effect of DM-102 has been evaluated in:
• ob/ob mice
• HFD mice
• Cavβ3-deficient (Cavβ3- −/−) mice
• Human Pancreatic Islet cells

18. Available Data regarding the IP
Phase I
• DM-102 was rapidly absorbed following SC administration
• Tmax: 45 h
• T1/2 – 6.5 days, metabolism- endonucleases, excretion- kidneys
• Doses tested previously: 25, 50, 100, 200mg (100 &above
not tolerated)
• Weight loss seen in 25, 50, 100 mg doses
• Few incidence of nausea, vomiting and infections
• Increase in Serum Alkaline Phosphatase with dose 100 & above
09-02-2021 18

19. 09-02-2021 19
Phase IIa (25 mg)
• Insulin 6.6 fold ↑ in First phase, 3 fold ↑ in second phase
• C-peptide 6.09 fold ↑ in First phase, 2.08 fold ↑ in Second
phase
• Glucagon ↓ in mean concentrations

20. A Phase IIb, Multicentre, Placebo-controlled,
Randomized, Double-Blind, Clinical Trial to Evaluate the Efficacy
and Safety of DM-102 in Subjects with
Type 2 Diabetes Mellitus
Protocol Version: 01/2019; dated 29/6/2019
Clinical Trial Site: Seth GS Medical College & K E M Hospital
Sponsor: KEMceutics Pvt. Ltd
Principle Investigator: Dr. MSD
Department of Endocrinology
Co-investigators: Dr. VK
Dept. of General Medicine
09-02-2021 20

21. • Study Co-ordinators: Dr ABD
Dr VVS
• Other sites: Additional 4 sites all over India
PART OR ALL OF THE INFORMATION IN THIS DOCUMENT MAY BE UNPUBLISHED MATERIAL AND SHOULD
BE TREATED AS CONFIDENTIAL AND PROPERTY OF KEMCEUTICS PVT. LTD, NOT TO BE DIVULGED TO
UNAUTHORIZED PERSONS IN ANY FORM, INCLUDING PUBLICATIONS AND PRESENTATIONS WITHOUT
THE EXPRESS WRITTEN CONSENT OF AUTHORIZED PERSON FROM KEMCEUTICS PVT. LTD.
09-02-2021 21

22. Objectives and Endpoints
Secondary objectives:
1. To evaluate the effect of DM-102 on body weight compared to Placebo
Primary objective
1. To evaluate the effect of DM-102 on Hemoglobin A1c (HbA1c) compared to
Placebo
Endpoint: Change in Hemoglobin A1c (HbA1c) from baseline to Week 12 with DM-
102 compared to placebo in subjects with T2DM.
09-02-2021 22
Endpoint: Mean change in body weight in kg from baseline to 12 weeks with DM-
102 compared to placebo

23. 2. To evaluate the effect of DM-102 on FPG compared to Placebo
3. To evaluate the effect of DM-102 on PPG compared to Placebo
09-02-2021 23
Endpoint: Change in 2h Post prandial plasma glucose (PPG) from
baseline to Weeks 3, 6, 9 and Week 12 with DM- 102 compared to
placebo
Endpoint: Change in fasting plasma glucose (FPG) from baseline to
Weeks 3, 6, 9 and 12 with DM- 102 compared to placebo

24. 4. To evaluate the effect of DM-102 on Lipids compared to Placebo
5. To evaluate the effect of DM-102 on Insulin secretion rate compared to
Placebo
Time points for AUC: 0, 5, 10, 30, 60, 120 minutes
09-02-2021 24
Endpoint: Change in Insulin Secretion (AUC0-10, AUC10-120) ) During IV
Hyperglycaemic Clamp –From Baseline to Week 12
[ Time Frame: Baseline, Week 12 ]
Endpoint: Changes in lipids [total cholesterol (TC), low-density lipoprotein cholesterol
(LDLC), high-density lipoprotein cholesterol (HDLC), non-high density cholesterol (non-
HDL-C) and triglycerides (TG)] from baseline to Week 12 with DM- 102 compared
to placebo

25. 09-02-2021 25
6. To evaluate the effect of DM-102 on C-peptide compared to
Placebo
Endpoint: Change in C-peptide (AUC0-10, AUC10-120) ) During IV
Hyperglycaemic Clamp –From Baseline to Week 12
[ Time Frame: Baseline, Week 12 ]
7. To evaluate the effect of DM-102 on Glucagon compared to
Placebo
Endpoint: Change in Glucagon (AUC0-10, AUC10-120) ) During IV
Hyperglycaemic Clamp –From Baseline to Week 12
[ Time Frame: Baseline, Week 12 ]

26. 09-02-2021 26
8. To evaluate the effect of DM-102 on the proportion of subjects achieving
HbA1c < 7.0% at Week 12 compared to placebo
Immunogenicity Objective
1. To evaluate the Incidence of Anti-ASO antibodies
Endpoint: Proportion of subjects achieving HbA1c < 7.0% at Week 12
with DM- 102 compared to placebo
Endpoint: No. of Patients developing the antibodies against DM-102 at
the end of 12 weeks

27. 09-02-2021 27
Safety Objective
To evaluate the safety and tolerability of DM-102 in subjects with T2DM
assessed by treatment emergent adverse events (TEAEs) and change in vital
signs and safety laboratory values.
AESI: Increased Serum Alkaline phosphatase levels
Endpoints:
a. The proportion of subjects with TEAE.
b. Changes in routine safety laboratory testing (i.e., hematology, chemistry) from
baseline to Week 3, 6, 9, 12.
c. The proportion of subjects with cardiovascular events including cardiovascular death,
nonfatal myocardial infarction, transient ischemic attack and non-fatal stroke,
hospitalization for unstable angina, urgent coronary revascularization intervention and
hospitalization for congestive heart failure
d. Incidence and Rate of Hypoglycemia

28. Study Design
• Randomized
• Double blind
• Placebo controlled
• 3 arm
• Parallel group
• Multicentre
• Phase IIb
09-02-2021 28

29. Sample Size Calculation
• Power- 90%
• Alpha error- 5%
• Standard Deviation- 1.1%
• Effect size- 0.8 % = 40
• Drop-out rate: 25%
• 50 per arm
09-02-2021 29
Total No of Patients in the study is 150
Sealed Envelope Ltd. 2012. Power calculator for continuous outcome superiority trial. [Accessed Sun Jun 23 2019]

30. Sample Size Calculation
Placebo v/s Group 1 (25mg) Placebo v/s Group 2 (50mg)
09-02-2021 30
Sealed Envelope Ltd. 2012. Power calculator for continuous outcome superiority trial. [Accessed Sun Jun 23 2019]

31. Inclusion Criteria
Subjects must satisfy all of the following criteria to be included in the
study:
• Able to provide written informed consent and willing to adhere to the
study visit schedule and treatment
• Diagnosed with Type 2 diabetes mellitus as defined in the American
Diabetes Association Standards of Medical Care in Diabetes 2018
• Screening HbA1c ≥ 7.0% and ≤ 10%
• Male or female ≥ 18 and ≤ 65 years of age
09-02-2021 31

32. 09-02-2021 32
• On stable (≥ 8 weeks) metformin monotherapy ≥ 1500 mg/day
or
On Dual Therapy with metformin (>1500mg/day) stable for atleast 4 weeks
prior to visit 1 and a second OHA and be willing to washout second OHA.
• Screening fasting C-peptide > 0.5 ng/mL
• Women of child bearing potential
• must be willing to use double barrier contraception for the entire study
• must have a negative pregnancy test
• Body mass index ≥ 18 kg/m2 and ≤ 30 kg/m2 at the Screening Visit

33. Exclusion Criteria
• History of type 1 diabetes and/or history of ketoacidosis
• History of insulin use for > 2 weeks within 2 months prior to the
Screening Visit
• during the second week of Run-in Period
• Two or more readings of fasting SMBG > 240 mg/dL or
• Worsening symptoms of hyperglycemia with one SMBG level of > 240 mg/dL,
confirmed by laboratory measurement
• Screening eGFR ≤ 60ml/minute
09-02-2021 33

34. 09-02-2021 34
• History of unstable angina, myocardial infarction, cerebrovascular
accident, transient ischemic attack, peripheral arterial event or any
revascularization procedure during the 6 months prior to the Screening
Visit or planned vascular procedures or surgery during study period
• History of congestive heart failure (CHF)
• Abuse of or dependence on prescription medications, illicit drugs, or
alcohol within the last 1 year
• Any history of a malignancy
• Has any condition or laboratory abnormality that, in the judgment of the
investigator, would make the subject inappropriate for entry into this trial.

35. 09-02-2021 35
Metformin
monotherapy(≥
1500 mg/day)
A1C ≥ 7.0%
and ≤ 10.0%
Metformin
(≥1500
mg/day)
+ other AHA
A1C ≥ 7.0%
and ≤ 10.0%
V1
Screening
V1A
Washout
Placebo
Run-in
V2
Week -2
V3
W0
V4
W1
V5
W2
V8
W6
V9
W9
V10
W12
V7
W4
V6
W3
Follow
up
Proceed
directly to V2
D/C other
OHA, enter
washout
R
DM-102 25 mg
DM-102 50 mg
Placebo
Background Metformin 1500 mg/day
Education and training
• Appropriate injection site locations
• Injection technique
• Signs and symptoms of local adverse
reactions
• Documentation and use of study related
devices
• Atleast 2 supervised placebo injections
2
w
e
e
k
s
≥ 8 weeks

36. Trial Period Screening Run-in Randomi
zation
Treatment Post treatment
Visit title Scree
ning
Wash-
out
Run-in Randomi
zation
Week 1 Week 2 Week 3 Week 4 Week 6 Week 9 Week
12
Discontinua
tion Visit
Follow-up
Day 14
Visit
number
1 1A 2 3 4 5 6 7 8 9 10 Discontinua
tion
14 day follow
up visit
Visit
window
+/- 3
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 3
days
+/- 3
days
+/- 3
days
+/- 3
days
Administrative procedures
Signed
informed
consent
X
Inclusion/e
xclusion
criteria
X X X
Assignmen
t of
randomizat
ion
number
X
Demograp
hic details
X
Contact
IVRS
X X X X X X X X X X X

37. 09-02-2021 37
Trial Period Screening Run-in Randomi
zation
Treatment Post treatment
Visit title Screen
ing
Wash-
out
Run-in Randomi
zation
Week 1 Week 2 Week 3 Week 4 Week 6 Week 9 Week
12
Discontinua
tion Visit
Follow-up
Day 14
Visit number 1 1A 2 3 4 5 6 7 8 9 10 Discontinua
tion
14 day follow
up visit
Visit window +/- 3
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 3
days
+/- 3
days
+/- 3
days
+/- 3
days
Clinical procedures/Assessments
Height X
Weight/Vital
signs
X X X X X X X X X X X X
Medical/Surgic
al history
X
Full body
physical
examination
assessment
X
Brief physical
examination
assessment
X X X X X X X X X
ECG(12 lead) X X X X X
Adverse events X---------------------------------------------------------------------------------------------------X X X

38. Trial Period Screening Run-in Randomi
zation
Treatment Post treatment
Visit title Screen
ing
Wash-
out
Run-in Randomi
zation
Week 1 Week 2 Week 3 Week 4 Week 6 Week 9 Week
12
Discontinua
tion Visit
Follow-up
Day 14
Visit number 1 1A 2 3 4 5 6 7 8 9 10 Discontinua
tion
14 day follow
up visit
Visit window +/- 3
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 3
days
+/- 3
days
+/- 3
days
+/- 3
days
Laboratory Parameters (Central Laboratory assessment)
HbA1c X X X X X X X
FPG X X X X X X X X
PPG X X X X X X X X
Lipid panel X X X X
Insulin,Glucagon
c-peptide AUC
X X
C-peptide X X
Pregnancy test X X X X X X X
TSH X X X X X X
HIV/HCV/HBsAg X
Immunogenicity
assay
X X X
Urine analysis X X X X

39. Trial Period Screening Run-in Randomi
zation
Treatment Post treatment
Visit title Screen
ing
Wash-
out
Run-in Randomi
zation
Week 1 Week 2 Week 3 Week 4 Week 6 Week 9 Week
12
Discontinua
tion Visit
Follow-up
Day 14
Visit number 1 1A 2 3 4 5 6 7 8 9 10 Discontinua
tion
14 day follow
up visit
Visit window +/- 3
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 3
days
+/- 3
days
+/- 3
days
+/- 3
days
Safety
laboratory
(Chemistry
,Hematology)
X X X X X X X X X
Drugs and devices
Washout
Second OHA,
X
Instruct Self-
Administration
Of Medication
X X
Supervised
Single-Blind
Placebo
Administration
X
Dispense
Double-Blind
IP
X X X X X X X

40. Trial Period Screening Run-in Randomi
zation
Treatment Post treatment
Visit title Screen
ing
Wash-
out
Run-in Randomi
zation
Week 1 Week 2 Week 3 Week 4 Week 6 Week 9 Week
12
Discontinua
tion Visit
Follow-up
Day 14
Visit number 1 1A 2 3 4 5 6 7 8 9 10 Discontinua
tion
14 day follow
up visit
Visit window +/- 3
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 3
days
+/- 3
days
+/- 3
days
+/- 3
days
Drugs and devices (contd...)
Witness Dose
of Blinded IP in
Clinic*
X X* X* X* X* X* X* X*
Concomitant
medications
Review
X X X X X X X X X X X X
Assess Trial
Medication
Compliance(Co
llect Unused
and Used IP)
X X X X X X X X X
Dispense blood
glucose meter
and electronic
Tab
X X

41. Trial Period Screening Run-in Randomi
zation
Treatment Post treatment
Visit title Screen
ing
Wash-
out
Run-in Randomi
zation
Week 1 Week 2 Week 3 Week 4 Week 6 Week 9 Week
12
Discontinua
tion Visit
Follow-up
Day 14
Visit number 1 1A 2 3 4 5 6 7 8 9 10 Discontinua
tion
14 day follow
up visit
Visit window +/- 3
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 1
days
+/- 3
days
+/- 3
days
+/- 3
days
+/- 3
days
Patient Education
Diet /Exercise
Counselling
X X X X X X X X
Instructions on
Hypoglycemia
Assessment
Log, symptoms
and
management
X X
Use of blood
glucose meter
and electronic
Tab
X X

42. Drug/ placebo administration
• Subcutaneous
• Weekly
• Timing: Preferably, Morning (Uniformity
over all doses)
• Doses if missed, should be taken as soon as
remembered & should be notified to the
sponsor
• Missing 2 doses is not allowed, patient will
be withdrawn
• Reminder for dosing will be sent through
Tab
09-02-2021 42

43. Electronic Tab
• Book an Appointment
• Maintain Hypoglycemia Log
• Notification of AE’s- will receive a call from the sponsor
• Enter Self Monitoring of Blood Glucose (SMBG) details
everyday
• Diet & exercise Instructions including videos.
• Reminder for exercise, dosing, SMBG
• Video demonstration of s.c Injection
09-02-2021 43

44. Supply and Storage of Investigational drugs
• Study drug and comparator drug will be supplied by KEMceutics Pvt Ltd
• Supply required till the next visit only will be dispensed
• Blinded single-use, 1 mL prefilled syringe with a fixed 27 gauge needle
providing 25/50mg of DM-102 or matching placebo injections
• Will bear study code, expiry date and name of the sponsor, batch number
of the drug, storage conditions and the statement “For Clinical Trial Use
Only”
09-02-2021 44

45. 09-02-2021 45
• Open label Metformin 500 mg (IR/XR) tablets
• All study medications (except metformin) will be stored at the trial site in
refrigerator (2°to 8°C ) with access restricted to the investigator and to
qualified delegated personnel.
• Transportation: in a cool carrier with an ice pack

46. Rescue Criteria & Medication
Hyperglycemia
Visit Interval Glycemic Thresholds
After Visit 3/Day 1 through
Visit 8/Week 6
FPG >270 mg/dL (15.0
mmol/L)
After Visit 8/Week 6 through FPG >240 mg/dL (13.3
mmol/L)
09-02-2021 46
Managed as considered appropriate by the investigator (selection of agent
and starting dose, timing of administration, and uptitration) to be
documented in eCRF.
US FDA. Guidance for Industry on Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and
Prevention; 2008.

47. Rescue Criteria & Medication (Contd.)
Hypoglcemia
• <54 mg/dL (<3 mmol/L) with or without symptoms of hypoglycemia or
• ≤70 mg/dL (≤3.9 mmol/L) with symptoms of hypoglycaemia
Medication:
If ≤ 70 mg: Fast-acting carbohydrate tablets (20g), recheck BG, if <70,
take again.
If ≤ 54 mg: IV Glucose or Glucagon (1mg IV/IM/SC)
09-02-2021 47
EMA. Guideline on clinical investigation of medicinal products in 4 the treatment or
prevention of diabetes mellitus; 2018.

48. Concomitant medication
Prohibited Medication Allowable Medication
All Antihyperglycemic medications with
the exception of background Metformin
Acetaminophen and NSAIDs
Corticosteroids (Treatment for ≥ 14
days/ repeated course)
Blood Pressure and Lipid-lowering
Medications*
Weight-loss Medications Hormonal Replacement Therapy*
Supplements and Traditional Medicines Thyroid Hormone Replacement Therapy*
Doses of these medications must remain stable during the double-blind treatment
period. Any dose adjustment if required should be made before randomization
09-02-2021 48

49. Withdrawal Criteria
• Subject’s decision to stop active participation
• Hyperglycemia: A consistent value of high FPG (defined as a repeat
measurement performed within 7 days of notification from the central
laboratory).
• Hypoglycemia: Repeated (2 or more episodes since the prior visit)
episode as measured by FPG or fingerstick glucose
• Missing ≥ 2 doses (To ensure Compliance ≥ 80%)
• Requirement for one of the prohibited medications
• Pregnancy
09-02-2021 49

50. 09-02-2021 50
• Abnormal liver function tests meeting criteria specified below
ALT or AST ≥8X ULN or ≥3X ULN with symptoms consistent with liver
injury
or
ALT or AST ≥5X ULN for 2 weeks or longer
• Elevation in circulating serum lipase ≥3X ULN that is associated with
clinical evidence of pancreatitis (e.g., symptoms of nausea/vomiting,
abdominal pain)
• Parameters of Renal Function
• Serum creatinine concentrations consistently ≥1.5 mg/dL in men or
≥1.4 mg/dL in women
• eGFR consistently <60 mL/min/1.73 m2

51. Statistical Analysis
• Safety: Modified intention to treat analysis.
• Efficacy: Per protocol
• P<0.05 will be considered significant
• Continuous Parametric Data: ANOVA followed by post-hoc Tukey’s test or
repeated measure ANOVA followed by post hoc Dunn’s test
• Continuous Non parametric data: Kruskal-Wallis test followed by Mann
Whitney U test with Bonferroni correction or Freidman test
• For proportions: Chi Square test/Fishers exact test
09-02-2021 51

52. 09-02-2021 52
Endpoint Parametric Test Nonparametric Test
Change in Hemoglobin A1c
(HbA1c) from baseline to
Week 12
ANOVA Kruskal-Wallis
Mean change in body weight
from baseline to 12 weeks
ANOVA Kruskal-Wallis
Change in fasting plasma
glucose (FPG) from baseline
to Weeks 3, 6, 9 and 12
ANOVA and Repeated
Measures ANOVA
Kruskal-Wallis
And Friedman test
Change in 2h Post prandial
plasma glucose (PPG) from
baseline to 3, 6, 9 and 12
ANOVA and Repeated
Measures ANOVA
Kruskal-Wallis
And Friedman test
Changes in lipids from
baseline to week 12
ANOVA Kruskal-Wallis

53. 09-02-2021 53
Endpoint Parametric Test Nonparametric Test
Proportion of subjects achieving
HbA1c < 7.0% at Week 12
Chi-square/Fisher’s exact
test
Chi-square/Fisher’s exact test
No. of Patients developing the
antibodies against DM-102 at
the end of 12 weeks
Chi-square/Fisher’s exact
test
Chi-square/Fisher’s exact test
Change in AUC of Glucagon, Insulin, c-peptide
= AUC at 12 week- AUC at baseline
Safety Data will be presented using Descriptive Statistics

54. Future Plan of evaluation
• Patient Population: Pre-diabetic patients, on life style and diet therapy
• Aim: To evaluate the effect of DM-102 in prevention of development of
diabetes
• Primary Endpoint: Time to development of Type 2 DM.
09-02-2021 54

55. Thank
you....