INVESTOR & ANALYST BREAKFAST November 18, 2019 1 Safe Harbor - - PowerPoint PPT Presentation

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INVESTOR & ANALYST BREAKFAST

November 18, 2019

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Safe Harbor

Certain statements contained in this material are forward-looking statements. These forward-looking statements are based on the current expectations of the management of Oramed only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward- looking statements, including the risks and uncertainties related to the progress, timing, cost, and results of clinical trials and product development programs; difficulties or delays in obtaining regulatory approval or patent protection for our product candidates; competition from other pharmaceutical or biotechnology companies; and

• ur ability to obtain additional funding required to conduct our research, development and commercialization

activities, and others, all of which could cause the actual results or performance of Oramed to differ materially from those contemplated in such forward-looking statements. Except as otherwise required by law, Oramed undertakes no obligation to publicly release any revisions to these forward-looking statements to reflect events

• r circumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detailed

description of the risks and uncertainties affecting Oramed, reference is made to Oramed's reports filed from time to time with the Securities and Exchange Commission. which involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of the company, or industry results, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Please refer to the company's filings with the Securities and Exchange Commission for a comprehensive list of risk factors that could cause actual results, performance or achievements of the company to differ materially from those expressed or implied in such forward-looking statements. Oramed undertakes no obligation to update or revise any forward-looking statements.

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Oramed Snapshot

▪ Proprietary oral protein delivery platform ▪ Diabetes first - initially targeting the lucrative insulin

• market. Additional huge markets in the pipeline

▪ Strong financial position over $37M in cash and investments, no debt1 ▪ Strong management team backed by world-class scientific experts ▪ Multiple value-creation events for this year ▪ NASDAQ/TASE: ORMP

1 As of May 31, 2019

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Agenda

8:30-9:15

▪ Opening Remarks - Nadav Kidron, Chief Executive Officer, Oramed Pharmaceuticals ▪ Review of the P2b Data - Joel Neutel, Director of Research Orange County Research Center & Kenneth Homer, Director of Biometrics, Integrium ▪ A Clinical Perspective - Ramachandra Naik, Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, SUNY Medical University, Syracuse ▪ Forward Looking Regulatory Pathway - Alexander Fleming, CEO Kinexum, Former Head of Clinical Review of Endocrine and Metabolic Drugs at FDA

9:15-9:45

▪ Q&A from Panel:

• Dr Neutel
• Dr Fleming
• Dr. Naik
• Dr. Miriam Kidron, Chief Scientific Officer, Oramed Pharmaceuticals

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Third Party Review of Phase IIb Data:

A Placebo-controlled, Multi-center Randomized, Phase 2b Study to Evaluate the Efficacy and Safety of ORMD-0801 in Type 2 Diabetes Mellitus Patients with Inadequate Glycemic Control on Oral Therapy

Joel Neutel, Director of Research Orange County Research Center & Kenneth Homer Director of Biometrics, Integrium

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▪ Primary Endpoint – mean change in HbA1c from baseline to Week 12 ▪ 39 sites screened subjects; 36 sites randomized subjects ▪ The Primary Treatment are the subjects who received QD, BID or TID Placebo and ORMD- 0801 32mg ▪ 273 subjects received primary treatment (included in Safety Population) ▪ 269 subjects received primary treatment and had Baseline HbA1c results (included in ITT Population) ▪ 233 subjects were included in the primary analysis (all sites excluding sites 13 and 20) ▪ 36 subjects were excluded from the primary analysis (sites 13 and 20 were excluded due to significant treatment by center interaction) ▪ 209 of the 233 subjects included in the primary analysis had Week 12 HbA1c results

Oramed Protocol ORA-D-015 Presentation of Results

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HbA1c – Observed Means – Primary Analysis

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HbA1c – Least Square Means – Primary Analysis

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HbA1c – Week 12 – Primary Analysis

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▪ Safety assessed by adverse event reporting including adverse events of special significance such as hypoglycemia ▪ Change from baseline in glycemic parameters measured using outpatient CGM ▪ Change in weight from baseline to week 12 of the treatment period

Secondary Endpoints

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Adverse Events Overall Summary

Combined Placebo (N=66) 32 mg QD (N=69) 32 mg BID (N=68) 32 mg TID (N=69) Number of Reported Adverse Events: 111 108 56 79 Number (%) of Subjects With at Least One: Treatment Emergent Adverse Event (TEAE) 46 (69.7) 38 (55.1) 27 (39.7) 35 (50.7) Severe TEAE 1 ( 1.5) 4 ( 5.8) 0 ( 0.0) 2 ( 2.9) Serious TEAE 3 ( 4.5) 5 ( 7.2) 0 ( 0.0) 3 ( 4.3) Drug-related TEAE 7 (10.6) 6 ( 8.7) 3 ( 4.4) 9 (13.0) Drug-related severe TEAE 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Drug-related serious TEAE 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) TEAE leading to withdrawal of study drug 1 ( 1.5) 0 ( 0.0) 1 ( 1.5) 1 ( 1.4) TEAE with outcome of death 1 ( 1.5) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0)

Safety Population

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Treatment Emergent Adverse Events Leading to Discontinuation

Combined Placebo (N=66) 32 mg QD (N=69) 32 mg BID (N=68) 32 mg TID (N=69) Number of Subjects with At Least One Adverse Event 1 ( 1.5) 0 ( 0.0) 1 ( 1.5) 1 ( 1.4) Cardiac Disorders 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) Myocardial Infarction 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) Gastrointestinal Disorders 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.4) Abdominal Pain 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.4) General Disorders & Administration Site Conditions 1 (1.5) 0 (0.0) 1 (1.5) 0 (0.0) Death 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) Fatigue 0 (0.0) 0 (0.0) 1 (1.5) 0 (0.0)

Safety Population

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Hypoglycemic Events

Hypoglycemic Events as reported on the Hypoglycemic / Hyperglycemic Log: Number of Hypoglycemic Events: ▪ Placebo – 21 ▪ ORMD-0801 QD – 16 ▪ ORMD-0801 BID – 4 ▪ ORMD-0801 TID – 32 Number of Subjects with at least 1 Hypoglycemic Event: ▪ Placebo – 4 / 66 (6.1%) ▪ ORMD-0801 QD – 6 / 69 (8.7%) ▪ ORMD-0801 BID – 3 / 68 (4.4%) ▪ ORMD-0801 TID – 6 / 69 (8.7%) Safety Population

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Continuous Glucose Monitoring – Area Under the Curve

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Serum Glucose (mg/dL) – Change from Baseline

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Summary of Weight Change (kg) at Week 12

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Summary of Diabetes Medication Usage During Study

There were a total of 68 subjects on Metformin Alone:

▪ Placebo – 16 (of which 14 have a Week 12 HbA1c) ▪ ORMD-0801 QHS – 20 (of which 16 have a Week 12 HbA1c) ▪ ORMD-0801 BID – 20 (of which 16 have a Week 12 HbA1c) ▪ ORMD-0801 TID – 12 (of which 8 have a Week 12 HbA1c)

Approximately 70% of the randomized patients were on 2 or more glucose lowering drugs

All Patients were on Metformin. Glucose lowering agents taken in addition to Metformin included: Glibenclamide, Glipizide, Empagliflozin, Pioglitazone, Glimepiride, Dapagliflozin, Sitagliptin, Glibomet, Ertugliflozin

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HbA1c Levels – Change from Baseline (Subjects with Baseline HbA1c > or <= 9%)

Baseline HbA1c Values > 9 (92 Subjects): ▪ ORMD-0801 QHS Placebo Adjusted = -0.72 ▪ ORMD-0801 BID Placebo Adjusted = -0.65 ▪ ORMD-0801 TID Placebo Adjusted = -0.54 Baseline HbA1c Values <= 9 (117 Subjects): ▪ ORMD-0801 QHS Placebo Adjusted = -0.41 ▪ ORMD-0801 BID Placebo Adjusted = -0.52 ▪ ORMD-0801 TID Placebo Adjusted = -0.41

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Discussion of Treatment by Site Interaction

When we analyze the data for one group of sites and get one answer which differs from the analysis of the second group of sites, in statistics this is called a treatment by site interaction. This is where we find ourselves.

• 0.06
• 0.59
• 0.06

0.85

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2 Placebo ORMD-0801 QD and BID Combined

Change (%) in HbA1c Least Squares Mean Change in HbA1c (%) at Week 12

Exc Sites 13 and 20 (233 Subjects) Sites 13 and 20 (36 Subjects)

• 0.2
• 0.6
• 1.15
• 0.18
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Placebo ORMD-0801 QD and BID Combined

Change (%) in HbA1c Observed Change in HbA1c (%) at Week 12

Exc Sites 13 and 20 (233 Subjects) Sites 13 and 20 (36 Subjects)

When analyzing the data excluding sites 13 and 20 (233 subjects), it shows that Placebo has a small least squares mean difference from 0 (-0.06) and active shows a much larger drop in least squares mean (-0.59). These two sites were

• bserved to have significant treatment by site interactions when analyzing the results of the linear model. Thus these

sites were selected based on statistical criteria. When analyzing the data for sites 13 and 20 (36 subjects), it shows that Placebo has a small least squares mean difference from 0 (-0.06) while active has a large increase in least squares mean (0.85). These are dramatically different results that lead to very different conclusions. Possible root causes of this difference have yet to be found.

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Handling Data not in Total Agreement

We are constantly bombarded by information that is not in total agreement.

34 2 4 8 12 16 20 24 28 32 36 Yes No Number of Sites

When asking 36 sites: Does ORMD-0801 Lower HbA1c at Week 12? ▪ 34 sites answer Yes, while 2 sites answer No.

233 36 54 108 162 216 270 Yes No Number of Subjects

▪ 233 subjects answer Yes, while 36 subjects answer No.

This type of results are presented to us consistently (on a daily basis), but we do not like to see this when we analyze clinical trial data.

When asking 269 sites: Does ORMD-0801 Lower HbA1c at Week 12?

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Discussion of Results for Sites 13 and 20 – HbA1c Results

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Discussion of Results for Sites 13 and 20 – Serum Glucose

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Summary of Results

Primary endpoint of reduction in HbA1c at Week 12 was achieved

▪ ORMD-0801 32mg QD showed a reduction of 0.54 after adjusting for placebo (p-value=0.036) ▪ ORMD-0801 32mg BID showed a reduction of 0.53 after adjusting for placebo (p-value=0.042)

Significant observed outcomes

▪ No increase in Adverse Events when compared to Placebo. ▪ No increase in Hypoglycemic Events when compared to Placebo. ▪ No weight gain when compared to Placebo

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Oral Insulin in the Therapeutic Armamentarium of Type 2 Diabetes: An Endocrinologist’s Perspective

Ramachandra G. Naik, MD Professor of Medicine Division of Endocrinology, Diabetes, and Metabolism Assistant Dean for Translational and Clinical Research Programs SUNY Upstate Medical University Syracuse, NY

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Learnings from the Oramed Phase IIb Study: Efficacy

▪ Study met the primary efficacy endpoint ▪ Clinically meaningful reduction in A1C from baseline to Week 12 ▪ Comparable A1C-lowering when administered once daily at bedtime (QHS) or twice daily (BID)

• Possible mechanism of QHS dosing could be suppression of increased overnight hepatic

glucose output, a key pathophysiologic abnormality in type 2 diabetes (T2D)

▪ Efficacy was demonstrated in subjects with inadequately controlled T2D on metformin alone or metformin + up to 2 additional oral antihyperglycemic agents (sulfonylurea, DPP-4 inhibitor, SGLT-2 inhibitor, thiazolidinedione)

• Potential to be used as a second-, third-, or fourth-line oral agent in the treatment of T2D

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Learnings from the Oramed Phase IIb Study: Safety

▪ Reassuring safety profile ▪ No drug related severe or serious Treatment Emergent Adverse Events (TRAE) ▪ No increased frequency of hypoglycemic episodes ▪ Weight neutrality

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ORMD-0801: Therapeutic Potential

▪ An oral formulation of insulin (ORMD-0801) may have significant benefits in fostering treatment acceptance and adherence ▪ The data support a unique mechanism of action of ORMD-0801: The oral route of administration replicates the normal physiology of insulin secretion and absorption through the portal vein followed by direct delivery to the liver ▪ The result is a more physiologic replacement of insulin, leading to an effective treatment with less risk of hypoglycemia and weight gain

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Standards of Medical Care in Diabetes – 2019

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Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2019. Diabetes Care 2019;42(Suppl. 1):S90-S102

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▪ If A1C is above target despite recommended first- line treatment and the patient has ASCVD or CKD: ▪ ASCVD Predominates: ▪ Add GLP-1 RA with proven CVD benefit, OR ▪ Add SGLT-2 inhibitor with proven CVD benefit (if eGFR adequate) ▪ If HF or CKD Predominates: ▪ Add SGLT-2 inhibitor with evidence of benefit ▪ If can’t take an SGLT-2 inhibitor, use a GLP-1 RA with proven CVD benefit

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▪ If A1C is above target despite recommended first- line treatment and the patient has ASCVD or CKD: ▪ ASCVD Predominates: ▪ Add GLP-1 RA with proven CVD benefit, OR ▪ Add SGLT-2 inhibitor with proven CVD benefit (if eGFR adequate) ▪ If HF or CKD Predominates: ▪ Add SGLT-2 inhibitor with evidence of benefit ▪ If can’t take an SGLT-2 inhibitor, use a GLP-1 RA with proven CVD benefit

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ORMD-0801: Forward Looking Regulatory Pathway

Alexander Fleming CEO Kinexum, Former Head of Clinical Review of Endocrine and Metabolic Drugs at FDA

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China License Deal: 500M patient potential

* Journal of the American Medical Association

▪ License: Exclusive right to ORMD-0801 in Greater China ▪ Licensee: Hefei Tianhui ("HTIT")

Owns with Sinopharm a state-of-the-art GMP API insulin manufacturing facility

• IND approved for oral insulin trials in China
• HTIT expected to begin clinical trials of ORMD-0801 in Q2 2019

▪ $50M Payments + Royalties:

• $12M in restricted stock (at premium)
• $38M milestone payments

▪ $33M received to date ▪ $17M expected over the next 2-3 years

• Up to 10% royalties on net sales

diabetic (10.9% of adult population) prediabetic (35.7% of adult population) Chinese diabetes market*

114M ~388M

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Q&A Panel

▪ Joel Neutel, Director of Research Orange County Research Center ▪ Kenneth Homer, Director of Biometrics, Integrium ▪ Ramachandra Naik, Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, SUNY Medical University, Syracuse ▪ Alexander Fleming, CEO Kinexum, Former Head of Clinical Review of Endocrine and Metabolic Drugs at FDA ▪ Dr. Miriam Kidron, Chief Scientific Officer, Oramed Pharmaceuticals

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Thank you