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Item 1. Business

2023-03-06 compared with 2021-11-24 · 400 added, 528 removed, 191 unchanged (83% of the section changed)

Description of Business

Research and Development

We are a pharmaceutical company

currently engaged in the research and development of innovative pharmaceutical solutions, including an oral insulin capsule to be used

for the treatment of individuals with diabetes, and the use of orally ingestible capsules or pills for delivery of other polypeptides.

We utilize Clinical Research Organizations, or CROs, to conduct our clinical studies.

We are currently a pharmaceutical

company engaged in the research and development of innovative pharmaceutical solutions with a technology platform that allows for the

oral delivery of therapeutic proteins.

Through our research and development

efforts, we have successfully developed an oral dosage form intended to withstand the harsh environment of the stomach and intestines

and effectively deliver active insulin or other proteins, such as Glucagon-like peptide-1, or GLP-1, leptin, and others.

The excipients

in the formulation are not intended to modify the proteins chemically or biologically, and the dosage form is designed to be safe to ingest.

We plan to continue to conduct clinical trials to show the effectiveness of our technology.

Oral insulin :

Our proprietary flagship product, an orally ingestible insulin capsule, or ORMD-0801, allows insulin to travel from the gastrointestinal

tract via the portal vein to the bloodstream, revolutionizing the manner in which insulin is delivered.

It enables the passage in a more

physiological manner than current delivery methods of insulin.

FDA Guidance:

2017, the U.S.

Food and Drug Administration, or FDA, instructed us that the regulatory pathway for the submission of ORMD-0801 would be

If approved the BLA pathway would grant us 12 years of marketing exclusivity for ORMD-0801, from the approval date, and an additional

six months of exclusivity may be granted to us if the product also receives approval for use in pediatric patients.

Phase IIb Study:

May 2018, we initiated a three-month dose-ranging Phase IIb clinical trial of ORMD-0801 (Cohort A).

This placebo controlled, randomized,

90-day treatment clinical trial was conducted on 269 type 2 diabetic, or T2D, patients in multiple centers throughout the United States

pursuant to an Investigational New Drug application, or IND, with the FDA.

The primary endpoints of the trial were to assess the safety

and evaluate the effect of ORMD-0801 on HbA1c levels over a 90-day treatment period.

Secondary endpoints of the trial included measurements

of fasting plasma glucose, or FPG, post-prandial glucose, or PPG levels, during a mixed-meal tolerance test, or MMTT, and weight.

May 2019, we initiated an extension of this protocol for approximately 75 T2D patients, who were dosed using a lower dosage of insulin

In November 2019, we announced positive results from the initial cohort of the Phase IIb trial.

Patients randomized in the trial to once-daily

ORMD-0801 achieved a statistically significant (p-value 0.036) reduction from baseline in HbA1c of 0.60% (0.54% with placebo adjustment).

This 0.54% reduction in HbA1c is clinically meaningful.

Treatment with ORMD-0801 demonstrated an excellent safety profile, with no serious

drug-related adverse events and with no increased frequency of hypoglycemic episodes when compared to placebo.

In addition, during this

90-day trial, no weight gain was observed.

In the initial cohort, 269 U.S.-based patients were enrolled and treated with a dose-increasing

16 mg initial dose, titrated to 24 mg per dose, and then titrated to 32 mg per dose.

Patients were randomized into three groups

to assess dosing frequency:

once-daily (32 mg per day), twice-daily (64 mg per day), thrice daily (96 mg per day).

There was a corresponding

placebo for each treatment arm.

Two hundred nine (209) patients completed treatment to the 12-week endpoint and were included in the data

analysis (24 subjects did not complete the full 12 weeks of treatment).

The twice-daily arms achieved statistically significant (p-value

0.042) reductions from baseline in HbA1c of 0.59% (0.53% with placebo adjustment).

The thrice-daily arm did not meet statistical significance

(p-value 0.093).

In addition, due to evidence of treatment-by-center interaction, two sites (36 patients (13.4% of enrolled subjects))

were excluded from the statistical analysis as they showed results opposite from the rest of the statistically significant results.

internal investigation as well as an independent investigation did not find a cause for such discrepancy.

In February 2020, we announced positive topline data from the second and final cohort of the Phase IIb trial with a different regimen

across three daily dose ranges (8 mg, 16 mg, 32 mg).

Patients randomized in the trial treated with 8 mg of ORMD-0801 once-daily achieved

a statistically significant (p-value 0.028) observed mean reduction of 1.29% from baseline and a least square mean reduction of 0.95%

from baseline, or 0.81% adjusted for placebo.

Patients who had HbA1c readings above 9% at baseline and received 8 mg of oral insulin once-daily

experienced a 1.26% reduction in HbA1c by week 12.

Treatment with ORMD-0801 at all doses demonstrated an excellent safety profile, with

no serious drug-related adverse events and with no increased frequency of hypoglycemic episodes or weight gain compared to placebo.

primary efficacy endpoint was a reduction in HbA1c at week 12.

Phase III Study :

Based on guidance received from the FDA as part of the end-of-phase II meeting process for our oral insulin candidate, ORMD-0801, we have

submitted to the FDA the protocols for our upcoming pivotal Phase III studies.

In line with the FDA’s expectations and recommendations,

we intend to conduct two Phase III studies concurrently in patients with T2D.

These studies involve about 1,125 patients to provide evidence

of ORMD-0801’s safety and efficacy in T2D patients over a treatment period of 6 to 12 months.

A geographically diverse patient population

will be recruited from multiple sites throughout the United States, Europe, and Israel.

Our Phase III study will be composed from 2 protocols:

ORA-D-013-1 :

This study will treat T2D patients with inadequate glycaemic control who are currently on 2 or 3 oral glucose-lowering agents.

study will recruit 675 patients from at least 75 clinical sites located throughout the U.S.

Patients will be randomized 1:1:1 in this

double-dummy study into cohorts of:

8 mg ORMD-0801 once-daily at night and placebo 45 minutes before breakfast;

8 mg ORMD-0801 twice-daily,

at night and 45 minutes before breakfast;

and placebo twice-daily, at night and 45 minutes before breakfast.

The primary endpoint of the

study is to evaluate the efficacy of ORMD-0801 compared to placebo in improving glycaemic control as assessed by HbA1c, with a secondary

efficacy endpoint of assessing the change from baseline in fasting plasma glucose at 26 weeks.

We initiated this trial in December 2020.

In November 2021, we announced that 75% of the 675 patients were enrolled and randomized.

ORA-D-013-2 :

This study will include T2D patients with inadequate glycaemic control who are managing their condition with either diet alone or with

diet and metformin monotherapy.

A total of 450 patients will be recruited through 36 sites in the U.S.

and 25 sites in Western Europe

Patients will be randomized 1:1 into two cohorts dosed with:

8 mg ORMD-0801 at night;

and placebo at night.

The primary endpoint

is to evaluate the efficacy of ORMD-0801 compared to placebo in improving glycaemic control as assessed by HbA1c over a 26-week treatment

period, with a secondary efficacy endpoint of assessing the change from baseline in fasting plasma glucose at 26 weeks.

We initiated this

trial in the U.S.

in March 2021.

In August 2021, we announced that over 25% of the 450 patients were enrolled and randomized.

We expect to receive the efficacy

data from the trials after patients have completed the first 6 months of treatment.

Safety will be further monitored as patients will

be exposed to the drug over an additional 6 months (total 12 months).

The trial’s topline results are expected in 2022 and we anticipate

filing a BLA with the FDA in 2023.

A BLA would grant us 12 years of marketing exclusivity from the date of approval in the U.S.

2020, we presented topline data of 8 patients from an open-label trial that assessed the safety, tolerability, and early effects of 16

mg ORMD-0801 (2x8 mg capsules) on liver fat in T2D, patients with nonalcoholic steatohepatitis, or NASH.

The 12-week dosing had no serious

adverse events and it induced an observed mean 6.9±6.8% reduction in liver fat content (p-value:

0.035), and the relative reduction

of 30%, as measured by MRI-derived proton density fat fraction, or MRI-PDFF.

In parallel, concentrations of gamma-glutamyltransferase

(GGT), a key marker of chronic hepatitis, were significantly lower after 12 weeks of treatment as compared to baseline (-14.6±13.1

In September 2020, we initiated an open label clinical

trial of our oral insulin capsule, ORMD-0801, for the treatment of NASH.

This 10 patient multi-center trial is comprised of three clinical

sites in Belgium.

The trial will measure change and percent change in MRI-PDFF from baseline to week 12.

In December 2020, we initiated a double blind,

placebo controlled clinical trial of our oral insulin capsule, ORMD-0801, for the treatment of NASH.

This 30 patient multi-center trial

is comprised of five clinical sites:

three in the U.S.

and two in Israel.

The trial will measure change and percent change in MRI-PDFF

from baseline to week 12.

In September 2021, we announced that over 50% of the patients were enrolled and randomized.

Oral Glucagon-Like Peptide-1:

Glucagon-Like Peptide-1, or GLP-1, is an incretin hormone, which stimulates the secretion of insulin from the pancreas.

In addition to

our flagship product, the ORMD-0801 insulin capsule, we use our technology for an orally ingestible GLP-1 capsule, or ORMD-0901.

In February 2019, we completed a Phase I pharmacokinetic

trial to evaluate the safety and pharmacokinetics of ORMD-0901 compared to placebo in healthy volunteers.

We initiated a follow-on trial

in T2D patients, in June 2021 in the U.S.

under an IND submitted to the FDA.

The following table gives

an overview of the above described primary R&D pipeline:

Our clinical trials are planned

in order to substantiate our results as well as for purposes of making future filings for drug approval.

We also plan to conduct further

research and development by deploying our proprietary drug delivery technology for the delivery of other polypeptides in addition to insulin,

and to develop other innovative pharmaceutical products.

On March 18, 2021, we entered into a license agreement,

or the Oravax License Agreement, with Oravax.

For more information about the Oravax License Agreement, please see below under “Out-Licensed

Oravax, Oramed’s 63% owned joint venture

combines our proprietary POD™ oral delivery technology and the novel vaccine technology of Premas Biotech Pvt.

Ltd., or Premas.

We are considering ways in which our shareholders could benefit more directly from Oravax, including potentially issuing some of our shares

in Oravax to our shareholders as a dividend, which would make Oravax a publicly held company that may in turn apply for listing on a stock

A single dose of Oravax’s oral vaccine produced

a significant antibody response in a preclinical in-vivo study.

Oravax’s novel vaccine technology may be a candidate for

protection against COVID-19 and its variants due to triple antigen targeting, easier distribution and ease of administration.

On October 29, 2021, we announced Oravax’s

oral COVID-19 vaccine has received clearance from the South African Health Products Regulatory Authority to initiate Phase I trial and

subsequently to commence patient enrollment in a first in human, Phase 1 clinical trial, for its oral COVID-19 vaccine.

Other Products

We are developing a new drug

candidate, a weight loss treatment in the form of an oral leptin capsule.

During the third quarter of the 2020 calendar year, we finalized

a proof of concept single-dose trial for this candidate to evaluate its pharmacokinetics and pharmacodynamics (glucagon reduction) in

10 type 1 adult diabetic patients without any safety issues.

Patients who received leptin on average had a decrease in glucose as compared

to the placebo group during the first 30-180 minutes following dosing.

At different time periods, the leptin treated patients on average

had glucagon values that were either lower than or similar to, those in the placebo group.

We are currently in the middle of a second

study of 15 type 1 adult diabetic patients who serve as both the active and placebo arms in this study, with anticipated results in the

fourth quarter of the 2021 calendar year.

efforts, we have developed an oral dosage form intended to withstand the harsh environment of the stomach and effectively deliver active

biological insulin or other proteins.

The excipients in the formulation are not intended to modify the proteins chemically or biologically,

and the dosage form is designed to be safe to ingest.

We plan to continue to conduct clinical trials to show the effectiveness of our

On January 11, 2023, we

announced that our Phase 3 trial, or the ORA-D-013-1 Phase 3 trial, did not meet its primary and secondary endpoints.

As a result, we

terminated both ORA-D-013-1 and ORA-D-013-2 Phase 3 clinical trials.

In parallel, we have initiated a comprehensive analysis of the data

to understand if there is a path forward for our oral insulin candidate.

We are examining our existing pipeline and have commenced an

evaluation process of potential strategic opportunities, with the goal of enhancing value for our stockholders.

Research and Development

Type 2 Diabetes :

conducted the ORA-D-013-1 Phase 3 trial on patients with type 2 diabetes, or T2D, with inadequate glycaemic control who were on two or

three oral glucose-lowering agents.

The primary endpoint of the trial was to evaluate the efficacy of our oral insulin capsule, ORMD-0801,

compared to placebo in improving glycaemic control as assessed by HbA1c, with a secondary efficacy endpoint of assessing the change from

baseline in fasting plasma glucose at 26 weeks.

On January 11, 2023, we announced that the ORA-D-013-1 Phase 3 trial did not meet its

primary and secondary endpoints.

Following the results of the ORA-D-013-1 Phase 3 trial, we also terminated the ORA-D-013-2 Phase 3 trial,

a second Phase 3 trial that included T2D patients with inadequate glycaemic control who were attempting to manage their condition with

either diet alone or with diet and metformin.

In December 2020,

we initiated a double blind, placebo controlled clinical trial of ORMD-0801 for the treatment of non-alcoholic steatohepatitis, or NASH,

On September 13, 2022, we reported positive top line results from this trial, demonstrating that ORMD-0801 was safe and well tolerated

at 8 mg twice daily dosing, meeting the primary endpoint of no difference in adverse events for ORMD-0801 compared to placebo.

also evaluated the effectiveness of ORMD-0801 in reducing liver fat content over the 12-week treatment period by observing several independent

All the measurements showed a consistent clinically meaningful trend in favor of ORMD-0801.

We are currently evaluating our

path forward for ORMD-0801 for NASH.

On March 18, 2021, we entered

into a license agreement, or the Oravax License Agreement, with Oravax, our 63% owned joint venture, pursuant to which we granted to Oravax

an exclusive, worldwide license of our rights in certain patents and related intellectual property relating to our proprietary oral delivery

technology to further develop, manufacture and commercialize oral vaccines for COVID-19 and other novel coronaviruses based on Premas

Ltd.’s, or Premas’s, proprietary vaccine technology involving a triple antigen virus like particle, or the Oravax

product, which was previously owned by Cystron Biotech LLC, and later acquired by Akers Biosciences Inc., or Akers.

Effective January

1, 2022, Oravax transferred its rights and obligations under the Oravax License Agreement to its wholly-owned subsidiary, Oravax Medical

For further details regarding the Oravax License Agreement, see note 12 to our audited consolidated financial statements.

In October 2021, Oravax’s

oral virus-like particle, or VLP, COVID-19 vaccine received clearance from the South African Health Products Regulatory Authority (SAPHRA)

to initiate a Phase 1 trial.

On December 14, 2021, Oravax screened and enrolled the first participant in this Phase 1 clinical trial.

The trial protocol was divided into two cohorts each comprised of 12 participants, with a 42-day safety waiting period between cohorts.

Due to several factors, including the fact that many volunteers did not qualify during screening due to prior asymptomatic COVID-19 infection

and other conditions, the rate of enrollment was slower than anticipated and as a result, we added an additional clinical site.

11, 2022, Oravax reported positive preliminary Phase 1 data for Cohort A of this trial, meeting primary and secondary endpoints of safety

and immunogenicity.

These results included significant antibody response (2-6 fold over baseline) as measured by multiple markers of immune

response to VLP vaccine antigens observed in the majority of the patients dosed, and no safety issues were observed, including mild symptoms.

Cohort B completed dosing on January 5, 2023 and data is expected in the first half of 2023.

On December 29, 2021, Oravax signed a cooperation

and purchase agreement for an initial pre-purchase of 10 million doses of oral COVID-19 vaccines with Tan Thanh Holdings to commercialize

the vaccine in Southeast Asia.

Raw Materials

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In July 2010, Oramed Ltd.

entered into the Manufacturing and Supply Agreement, or MSA, with Sanofi-Aventis Deutschland GMBH, or Sanofi-Aventis.

According to the

MSA, Sanofi-Aventis will supply Oramed Ltd.

entered into the Manufacturing and Supply Agreement with Sanofi-Aventis Deutschland GMBH, or Sanofi-Aventis.

According to the agreement,

Sanofi-Aventis supplies Oramed Ltd.

with specified quantities of recombinant human insulin to be used for clinical trials.

We purchase, pursuant to separate

agreements with third parties, the raw materials required for the manufacturing of our oral capsule.

We generally depend upon a limited

number of suppliers for the raw materials.

Although alternative sources of supply for these materials are generally available, we could

incur significant costs and disruptions if we need to change suppliers.

The termination of our relationships with our suppliers or the

failure of these suppliers to meet our requirements for raw materials on a timely and cost-effective basis could have a material adverse

effect on our business, prospects, financial condition and results of operations.

We have purchased, pursuant

to separate agreements with third parties, the raw materials required for the manufacturing of our oral capsule.

We generally depend upon

a limited number of suppliers for the raw materials.

Although alternative sources of supply for these materials are generally available,

we could incur significant costs and disruptions if we need to change suppliers.

The termination of our relationships with our suppliers

or the failure of these suppliers to meet our requirements for raw materials on a timely and cost-effective basis could have a material

adverse effect on our business, prospects, financial condition and results of operations.

Market Overview

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Diabetes is a leading cause of blindness, kidney failure, heart attack, stroke and amputation.

The latest report

of the ADA that analyzed the economic costs of diabetes in the U.S in 2017 indicates that the total cost of diagnosed diabetes in the

United States in 2017 was $327 billion.

Intellectual Property

Impact of COVID-19

We do not expect any material

impact on our development timeline and our liquidity due to COVID-19.

However, we experienced approximately six months of delays in clinical

trials due to slow-downs of recruitment for trials generally.

On the other hand, Oravax continues to develop its oral vaccine, the demand

for which may be reduced if COVID-19 continues to abate.

We continue to assess the effect on our operations by monitoring the status of

Intellectual Property and Patents

We own a portfolio of patents

and patent applications covering our technologies, and we are aggressively protecting these technology developments on a worldwide basis.

We are led by an experienced management team knowledgeable in the treatment of diabetes.

Our Chief Scientific Officer, Miriam Kidron,

PhD, is a recognized pharmacologist and a biochemist and the innovator primarily responsible for our oral insulin technology development

and know-how.

Scientific Advisory

Our management team has access to our internationally recognized Scientific Advisory Board whose members are thought-leaders

in their respective areas.

The Scientific Advisory Board is comprised of Dr.

Roy Eldor, Dr.

Ele Ferrannini, Dr.

Alexander Fleming, Dr.

Avram Hershko, Dr.

Harold Jacob, Dr.

Julio Rosenstock and Dr.

We plan to ultimately seek

a strategic commercial partner, or partners, with extensive experience in the development, commercialization, and marketing of insulin

applications and/or other orally digestible drugs.

We anticipate such partner or partners would be responsible for, or substantially support,

late-stage clinical trials (Phase III) to increase the likelihood of obtaining regulatory approvals and registrations in the appropriate

markets in a timely manner.

We further anticipate that such partner, or partners, would also be responsible for sales, marketing and support

of our products in these markets.

Such planned strategic partnership, or partnerships, may provide a marketing and sales infrastructure

for our products as well as financial and operational support for global clinical trials, post marketing studies, label expansions and

other regulatory requirements concerning future clinical development.

In 2015, we successfully executed this strategy when we, Oramed

and HTIT entered into a Technology License Agreement pursuant to which we granted HTIT an exclusive commercialization license in

the territory of the People’s Republic of China, Macau and Hong Kong, or the Territory, related to our oral insulin capsule, ORMD-0801.

Any future strategic partner, or partners, may also provide capital and expertise that would enable the partnership to develop new oral

dosage forms for other polypeptides.

While our strategy is to partner with an appropriate party, no assurance can be given that we will

in fact be able to reach an agreeable partnership with any third party.

Under certain circumstances, we may determine to develop one or

more of our oral dosage forms on our own, either world-wide or in select territories.

In line with our strategy,

we have entered into a joint venture focused on the development of novel oral COVID-19 vaccines, based on our proprietary oral delivery

technology and our partners’ novel vaccine technology.

In addition to developing

our own oral dosage form drug portfolio, we are, on an on-going basis, considering in-licensing and other means of obtaining additional

technologies to complement and/or expand our current product portfolio.

Our goal is to create a well-balanced product portfolio that will

enhance and complement our existing drug portfolio.

Potential Material Impact of COVID-19

The COVID-19 pandemic has

negatively impacted the global economy, disrupted consumer spending and global supply chains and created significant volatility and disruption

of financial markets.

Although to date the COVID-19 pandemic has not had a material adverse effect on us, the COVID-19 pandemic may have

a material adverse effect on our business and financial performance in the future.

The extent of the impact of the COVID-19 pandemic,

including our ability to execute our business strategies as planned, will depend on future developments, including the duration and severity

of the pandemic, which are highly uncertain and cannot be predicted.

Although, as of the date of

this Annual Report on Form 10-K, we do not expect any material impact on our long-term activity, the extent to which COVID-19 impacts

our business will depend on future developments, which are highly uncertain and cannot be predicted, including new information which may

emerge concerning the severity of COVID-19 and the actions to contain COVID-19 or treat its impact, among others.

Patents and Licenses

We maintain a proactive intellectual

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Expiration dates for pending patents, if granted, will fall between 2026 and 2039.

We hold 87 patents, one of

which was issued during the fiscal year ended August 31, 2021, or fiscal 2021, including patents issued by the United States, Swiss, German,

French, U.K., Italian, Netherlands, Swedish, Spanish, Australian, Israeli, Japanese, New Zealand, South African, Russian, Canadian, Hong

Kong, Chinese, European and Indian patent offices that cover a part of our technology, which allows for the oral delivery of proteins;

patents issued by the Australian, Canadian, European, Austrian, Belgian, French, German, Irish, Italian, Luxembourg, Monaco, Netherlands,

Norwegian, Spanish, Swedish, Swiss, U.K., Israeli, New Zealand, South African, Russian and Japanese patent offices that cover part of

We hold 112 patents, twenty

of which were issued during the fiscal year ended December 31, 2022, including patents issued by the United States, Swiss, German, French,

U.K., Italian, Netherlands, Swedish, Spanish, Australian, Israeli, Japanese, New Zealand, South African, Russian, Canadian, Hong Kong,

Chinese, European and Indian patent offices that cover a part of our technology, which allows for the oral delivery of proteins;

issued by the Australian, Canadian, European, Austrian, Belgian, French, German, Irish, Italian, Luxembourg, Monaco, Netherlands, Norwegian,

Spanish, Swedish, Swiss, U.K., Israeli, New Zealand, South African, Russian, Brazilian and Japanese patent offices that cover part of

our technology for the oral delivery of exenatide;

7 unchanged sentences

Our patent strategy is as

Aggressively protect all current and future technological developments to assure strong and broad protection by filing patents and/or continuations in part as appropriate,

Protect technological developments at various levels, in a complementary manner, including the base technology, as well as specific applications of the technology, and

Establish comprehensive coverage in the United States and in all relevant foreign markets in anticipation of future commercialization opportunities.

● Aggressively

protect all current and future technological developments to assure strong and broad protection by filing patents and/or continuations

in part as appropriate,

technological developments at various levels, in a complementary manner, including the base technology, as well as specific applications

of the technology, and

comprehensive coverage in the United States and in all relevant foreign markets in anticipation of future commercialization opportunities.

Trademarks and Trade Secrets

We have trademark applications

pending in Israel, with Corresponding international trademark applications in Australia, Brazil, Canada, China, Colombia, the European

Union, India, Indonesia, Japan, Kazakhstan, Korea, Malaysia, Mexico, New Zealand, Norway, Oman, Philippines, Russia, Singapore, Switzerland,

Thailand, Turkey, Ukraine, United Arab Emirates, United Kingdom, U.S.A., Uzbekistan and Vietnam.

We also rely on trade secrets

1 unchanged sentence

Our policy is to require our employees, consultants,

contractors, manufacturers, outside scientific collaborators and sponsored researchers, our board of directors, or our Board, technical

review board and other advisors, to execute confidentiality agreements upon the commencement of employment or consulting relationships

These agreements provide that all confidential information developed or made known to the individual during the course of the

individual’s relationship with us is to be kept confidential and not disclosed to third parties except in specific limited circumstances.

We also require signed confidentiality or material transfer agreements from any company that is to receive our confidential information.

In the case of employees, consultants and contractors, the agreements provide that all inventions conceived by the individual while rendering

services to us shall be assigned to us as the exclusive property of the Company.

There can be no assurance, however, that all persons

who we desire to sign such agreements will sign, or if they do, that these agreements will not be breached, that we would have adequate

remedies for any breach, or that our trade secrets or unpatentable know-how will not otherwise become known or be independently developed

by competitors.

contractors, manufacturers, outside scientific collaborators and sponsored researchers, our Board, technical review board and other advisors,

to execute confidentiality agreements upon the commencement of employment or consulting relationships with us.

These agreements provide

that all confidential information developed or made known to the individual during the course of the individual’s relationship with

us is to be kept confidential and not disclosed to third parties except in specific limited circumstances.

We also require signed confidentiality

or material transfer agreements from any company that is to receive our confidential information.

In the case of employees, consultants

and contractors, the agreements provide that all inventions conceived by the individual while rendering services to us shall be assigned

to us as the exclusive property of the Company.

There can be no assurance, however, that all persons who we desire to sign such agreements

will sign, or if they do, that these agreements will not be breached, that we would have adequate remedies for any breach, or that our

trade secrets or unpatentable know-how will not otherwise become known or be independently developed by competitors.

Out-Licensed Technology

In June 2010, Oramed Ltd.

entered into a joint venture agreement with D.N.A Biomedical Solutions Ltd., or D.N.A, for the establishment of Entera Bio Ltd., or Entera.

Under the terms of a license

agreement, as amended, that was entered into between Oramed Ltd.

and Entera in August 2010, we out-licensed technology to Entera, on an

exclusive basis, for the development of oral delivery drugs for certain indications to be agreed upon between the parties.

The out-licensed

technology differs from our main delivery technology that is used for oral insulin and GLP-1 analog and is subject to different patent

applications.

Entera’s initial development effort is for an oral formulation for the treatment of osteoporosis.

In March 2011, we

entered into a patent transfer agreement, or the Patent Transfer Agreement, to replace the original license agreement pursuant to which

assigned to Entera all of its right, title and interest in and to the patent application that it had licensed to Entera in

Under this agreement, Oramed Ltd.

is entitled to receive from Entera royalties of 3% of Entera’s net revenues and a

license back of that patent application for use in respect of diabetes and influenza.

In March 2011, we also consummated

a transaction with D.N.A, whereby we sold to D.N.A 47% of Entera’s outstanding share capital on an undiluted basis, retaining a

3% interest as of March 2011.

In consideration for the shares sold to D.N.A, we received, among other payments, ordinary shares of D.N.A.

The D.N.A ordinary shares are traded on the Tel Aviv Stock Exchange and its quoted price is subject to market fluctuations, and may, at

times, have a price below the value on the date we acquired such shares.

In addition, the ordinary shares of D.N.A have historically experienced

low trading volume;

as a result, there is no guarantee that we will be able to resell the ordinary shares of D.N.A at the prevailing market

During the years ended August 31, 2021, 2020 and 2019, we did not sell any of the D.N.A ordinary shares.

As of August 31, 2021,

we held approximately 1.7% of D.N.A’s outstanding ordinary shares.

On December 11, 2018, Entera

announced that it had entered into a research collaboration and license agreement, or the Amgen License, with Amgen Inc.

related to research

of inflammatory disease and other serious illnesses.

As reported by Entera, under the terms of the Amgen License, Entera will receive

a modest initial technology access fee from Amgen and will be responsible for preclinical development at Amgen’s expense.

will be eligible to receive up to $270,000,000 in aggregate payments, as well as tiered royalties up to mid-single digits, upon achievement

of various clinical and commercial milestones if Amgen decides to move all of these programs forward.

To the extent the Amgen License

results in net revenues as defined in the Patent Transfer Agreement, Oramed Ltd.

In June 2010, our wholly-owned

subsidiary, Oramed Ltd., entered into a joint venture agreement with DNA GROUP (T.R.) Ltd.

(formerly D.N.A Biomedical Solutions Ltd.),

or DNA, for the establishment of Entera Bio Ltd., or Entera.

In March 2011, Oramed Ltd.

sold shares of Entera to DNA, retaining 117,000 ordinary shares (after giving effect to a stock split by Entera in July 2018).

In consideration

for the shares sold to DNA, the Company received, among other payments, ordinary shares of DNA (see also note 3 to our audited consolidated

financial statements).

As part of this agreement,

entered into a patent transfer agreement, or the Patent Transfer Agreement, according to which Oramed Ltd.

assigned to Entera

all of its rights to a patent application related to the oral administration of proteins that it has licensed to Entera since August 2010,

in return for royalties of 3% of Entera’s net revenues and a license back of that patent application for use in respect of diabetes

and influenza.

As of December 31, 2022, Entera had not paid any royalties to Oramed Ltd.

On December 11, 2018, Entera announced that it

had entered into a research collaboration and license agreement with Amgen, Inc., or Amgen.

To the extent that the license granted to

Amgen results in net revenues as defined in the Patent Transfer Agreement, Oramed Ltd.

will be entitled to the aforementioned royalties.

On November 30, 2015, we,

and HTIT entered into a Technology License Agreement, or TLA, and on December 21, 2015, these parties entered into an Amended

and Restated Technology License Agreement that was further amended by the parties on June 3, 2016 and July 24, 2016, or the License Agreement.

According to the License Agreement, we granted HTIT an exclusive commercialization license in the Territory, related to our oral insulin

capsule, ORMD-0801, or the Product.

Pursuant to the License Agreement, HTIT will conduct, at its own expense, certain pre-commercialization

and regulatory activities with respect to our subsidiary’s technology and ORMD-0801 capsule, and will pay (i) royalties of 10% on

net sales of the related commercialized products to be sold by HTIT in the Territory, or Royalties, and (ii) an aggregate of $37.5 million,

of which $3 million was payable immediately, $8 million will be paid subject to our entry into certain agreements with certain third parties,

and $26.5 million will be payable upon achievement of certain milestones and conditions.

In the event that we will not meet certain conditions,

the Royalties rate may be reduced to a minimum of 8%.

Following the final expiration of our patents covering the technology in the Territory

in 2033, the Royalties rate may be reduced, under certain circumstances, to 5%.

The royalty payment obligation shall apply during the

period of time beginning upon the first commercial sale of the Product in the Territory, and ending upon the later of (i) the expiration

of the last-to-expire licensed patents in the Territory;

and (ii) 15 years after the first commercial sale of the Product in the Territory,

or the Royalty Term.

The License Agreement shall remain in effect until the expiration of the Royalty Term.

The License Agreement contains

customary termination provisions.

Through August 31, 2021, we received aggregate milestone payments of $20.5 million out of the aggregate

amount of $37.5 million.

As part of a consulting agreement with a third party dated February 15, 2011, Oramed Ltd.

is obliged to pay this third party royalties

of 8% of the net royalties received in respect of the patent that was sold to Entera in March 2011.

During the years ended December 31,

2022, 2021 and four month period ended December 2021, we did not sell any of DNA’s ordinary shares.

As of December 31, 2022, we

held approximately 1.4% of DNA’s outstanding ordinary shares and approximately 0.4% of Entera’s outstanding ordinary shares.

On November 30, 2015, we entered into a Technology License Agreement,

or TLA, with Hefei Tianhui Incubator of Technologies Co., Ltd., or HTIT, and on December 21, 2015, these parties entered into an Amended

and Restated Technology License Agreement that was further amended by the parties on June 3, 2016 and July 24, 2016, or the HTIT License

According to the HTIT License Agreement, we granted HTIT an exclusive commercialization license in the territory of the People’s

Republic of China, Macau and Hong Kong, related to our oral insulin capsule, ORMD-0801, or the Product.

Pursuant to the HTIT License Agreement,

HTIT will conduct, at its own expense, certain pre-commercialization and regulatory activities with respect to our technology and ORMD-0801

capsule, and will pay (i) royalties of 10% on net sales of the related commercialized products to be sold by HTIT in the territory, or

Royalties, and (ii) an aggregate of $37.5 million, of which $3 million was payable immediately, $8 million will be paid subject to our

entry into certain agreements with certain third parties, and $26.5 million will be payable upon achievement of certain milestones and

In the event that we will not meet certain conditions, the Royalties rate may be reduced to a minimum of 8%.

Following the

final expiration of our patents covering the technology in the territory in 2033, the Royalties rate may be reduced, under certain circumstances,

The royalty payment obligation shall apply during the period of time beginning upon the first commercial sale of the Product in

the territory, and ending upon the later of (i) the expiration of the last-to-expire licensed patents in the territory;

and (ii) 15 years

after the first commercial sale of the Product in the territory.

The HTIT License Agreement shall remain in effect until the expiration

of the royalty term.

The HTIT License Agreement contains customary termination provisions.

Through December 31, 2022, we received aggregate

milestone payments of $20.5 million out of the aggregate amount of $37.5 million.

On August 21, 2020, we received

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with HTIT in an attempt to reach a mutually agreeable solution.

We are currently evaluating with HTIT a path forward to continue our collaboration,

following the results of our ORA-D-013-1 Phase 3 trial.

Oravax License

On March 18, 2021, we entered into the Oravax License

Agreement with Oravax, pursuant to which we will grant to Oravax an exclusive, worldwide license , or the License, under our rights in

certain patents and related intellectual property in which Oravax will receive certain rights relating to our proprietary oral delivery

technology to further develop, manufacture and commercialize oral vaccines for COVID-19 and other novel coronaviruses based on Premas’s

proprietary vaccine technology involving a triple antigen virus like particle, or the Oravax Product, which was previously owned by Cystron

Biotech LLC, or Cystron, and later acquired by Akers Biosciences Inc., or Akers.

In consideration for the grant

of the License, the Oravax License Agreement provides that we will receive (i) royalties equal to 7.5% on net sales, as defined in the

Oravax License Agreement, of each product commercialized by Oravax, its affiliates and permitted sublicensees related to the License during

the term specified in the Oravax License Agreement, (ii) sublicensing fees equal to 15% of any non-sales-based consideration received

by Oravax from a permitted sublicensee and (iii) other payments ranging between $25 million to $100 million, based on certain sales milestones

being achieved by Oravax.

of the license under the Oravax License Agreement, we will receive (i) royalties equal to 7.5% on net sales, as defined in the Oravax

License Agreement, of each product commercialized by Oravax, its affiliates and permitted sublicensees related to the license during the

term specified in the Oravax License Agreement, (ii) sublicensing fees equal to 15% of any non-sales-based consideration received by Oravax

from a permitted sublicensee and (iii) other payments ranging between $25 million to $100 million, based on certain sales milestones being

achieved by Oravax.

The parties further agreed to establish a development and steering committee, which will consist of three members,

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representing 63% of the common stock of Oravax for the aggregate amount of $1.5 million.

Akers agreed to contribute to Oravax $1.5 million

in cash and substantially all of the assets of Cystron, including a license agreement to Premas’s novel vaccine technology.

Kidron, the Company’s President and Chief Executive Officer, was one of the former members of Cystron.

See note 12 to the financial

Akers contributed $1.5 million in cash to Oravax

and a license agreement to the Oravax product.

Nadav Kidron, the Company’s President and Chief Executive Officer, was one of the

former members of Cystron.

See note 12 to our audited consolidated financial statements.

Medicox License

On November 13, 2022, we

entered into a distribution license agreement with Medicox Co., Ltd., or Medicox.

an emerging biotech company with a consortium of proven

partnerships in the Republic of Korea.

The agreement grants Medicox the exclusive license to apply for regulatory approval and distribute

ORMD-0801 for ten years in the Republic of Korea.

Medicox will comply with agreed distribution targets and will purchase ORMD-0801 at

an agreed upon transfer price per capsule.

In addition, Medicox will pay Oramed up to $15 million in developmental milestones, $2 million

of which have already been received by Oramed to date, and up to 15% royalties on gross sales.

Medicox will also be responsible for gaining

regulatory approval in the Republic of Korea.

We are currently evaluating

with Medicox a path forward to continue our collaboration, following the results of our ORA-D-013-1 Phase 3 trial.

Government Regulation

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The process of conducting

clinical studies is highly regulated by the FDA, as well as by other governmental and professional bodies.

clinical trials is highly regulated by the FDA, as well as by other governmental and professional bodies.

Below we describe the principal

framework in which clinical studies are conducted, as well as describe a number of the parties involved in these studies.

framework in which clinical trials are conducted, as well as describe a number of the parties involved in these trials.

Before commencing

human clinical studies, the sponsor of a new drug or therapeutic product must submit an IND application to the FDA.

human clinical trials, the sponsor of a new drug or therapeutic product must submit an IND application to the FDA.

The application contains,

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Institutional Review Board .

An institutional review board is an independent committee of professionals and lay persons which reviews clinical research studies involving

An institutional review board is an independent committee of professionals and lay persons which reviews clinical research trials involving

human beings and is required to adhere to guidelines issued by the FDA.

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Its members are not appointed by the FDA.

All clinical studies must be approved by an institutional

All clinical trials must be approved by an institutional

review board.

The institutional review board’s role is to protect the rights of the participants in the clinical studies.

The institutional review board’s role is to protect the rights of the participants in the clinical trials.

the protocols to be used, the advertisements which the company or CRO conducting the study proposes to use to recruit participants, and

the form of consent which the participants will be required to sign prior to their participation in the clinical studies.

the form of consent which the participants will be required to sign prior to their participation in the clinical trials.

Clinical Trials .

Human clinical

studies or testing of a potential product are generally done in three stages known as Phase I through Phase III testing.

the phases are derived from the regulations of the FDA.

Generally, there are multiple studies conducted in each phase.

Phase I studies involve

testing a drug or product on a limited number of healthy or patient participants, typically 24 to 100 people at a time.

Phase I studies

determine a product’s basic safety and how the product is absorbed by, and eliminated from, the body.

This phase lasts an average

of six months to a year.

trials involve testing of no more than 300 participants at a time who may suffer from the targeted disease or condition.

testing typically lasts an average of one to two years.

In Phase II, the drug is tested to determine its safety and effectiveness

for treating a specific illness or condition.

Phase II testing also involves determining acceptable dosage levels of the drug.

II studies may be split into Phase IIa and Phase IIb sub-studies.

Phase IIa studies may be conducted with patient volunteers and are

exploratory (non-pivotal) studies, typically designed to evaluate clinical efficacy or biological activity.

Phase IIb studies are

conducted with patients defined to evaluate definite dose range and evaluate efficacy.

If Phase II studies show that a new drug has

an acceptable range of safety risks and probable effectiveness, a company will generally continue to review the substance in Phase

Phase III studies

clinical trials or testing of a potential product are generally done in three stages known as Phase 1 through Phase 3 testing.

of the phases are derived from the regulations of the FDA.

Generally, there are multiple trials conducted in each phase.

Phase 1 trials

involve testing a drug or product on a limited number of healthy or patient participants, typically 24 to 100 people at a time.

1 trials determine a product’s basic safety and how the product is absorbed by, and eliminated from, the body.

This phase lasts

an average of six months to a year.

Phase 2 trials

involve testing of no more than 300 participants at a time who may suffer from the targeted disease or condition.

Phase 2 testing typically

lasts an average of one to two years.

In Phase 2, the drug is tested to determine its safety and effectiveness for treating a specific

illness or condition.

Phase 2 testing also involves determining acceptable dosage levels of the drug.

Phase 2 trials may be split into

Phase 2a and Phase 2b sub-trials.

Phase 2a trials may be conducted with patient volunteers and are exploratory (non-pivotal) trials, typically

designed to evaluate clinical efficacy or biological activity.

Phase 2b trials are conducted with patients defined to evaluate definite

dose range and evaluate efficacy.

If Phase 2 trials show that a new drug has an acceptable range of safety risks and probable effectiveness,

a company will generally continue to review the substance in Phase 3 trials.

Phase 3 trials

involve testing large numbers of participants, typically several hundred to several thousand persons.

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and long-term safety on a large scale.

These studies generally last two to three years.

Phase III studies are conducted at multiple locations

Like the other phases, Phase III requires the site to keep detailed records of data collected and procedures performed.

These trials generally last two to three years.

Phase 3 trials are conducted at multiple locations

Like the other phases, Phase 3 requires the site to keep detailed records of data collected and procedures performed.

Biological License Application .

The results of the clinical trials for a biological product are submitted to the FDA as part of a BLA.

Following the completion of Phase

III studies, assuming the sponsor of a potential product in the United States believes it has sufficient information to support the safety

and effectiveness of its product, the sponsor will generally submit a BLA to the FDA requesting that the product be approved for marketing.

The application is a comprehensive, multi-volume filing that includes the results of all clinical studies, information about the drug’s

composition, and the sponsor’s plans for producing, packaging and labeling the product.

The FDA’s review of an application

can take a few months to many years, with the average review lasting 18 months.

Once approved, drugs and other products may be marketed

in the United States, subject to any conditions imposed by the FDA.

Approval of a BLA provides 12 years of exclusivity in the U.S.

The FDA may require

that the sponsor conduct additional clinical trials following new drug approval.

The purpose of these trials, known as Phase IV studies,

is to monitor long-term risks and benefits, study different dosage levels or evaluate safety and effectiveness.

In recent years, the FDA

has increased its reliance on these trials.

Phase IV studies usually involve thousands of participants.

Phase IV studies also may be initiated

by the company sponsoring the new drug to gain broader market value for an approved drug.

Similar to the U.S., a European

sponsor of a biological product may submit a Marketing Approval Application to the EMA for the registration of the product.

process in Europe consists of several stages, which together are summed up to 210 days from the time of submission of the application

(net, without periods in which the sponsor provides answers to questions raised by the agency) following which, a Marketing Approval may

During the approval process, the sponsor’s manufacturing facilities will be audited in order to assess Good Manufacturing

Practice compliance.

The results of the clinical trials for a biological product are submitted to the FDA as part of a Biological License Application, or BLA.

Following the completion of Phase 3 trials, assuming the sponsor of a potential product in the United States believes it has sufficient

information to support the safety and effectiveness of its product, the sponsor will generally submit a BLA to the FDA requesting that

the product be approved for marketing.

The application is a comprehensive, multi-volume filing that includes the results of all clinical

trials, information about the drug’s composition, and the sponsor’s plans for producing, packaging and labeling the product.

The FDA’s review of an application can take a few months to many years, with the average review lasting 18 months.

Once approved,

drugs and other products may be marketed in the United States, subject to any conditions imposed by the FDA.

Approval of a BLA provides

12 years of exclusivity in the U.S.

require that the sponsor conduct additional clinical trials following new drug approval.

The purpose of these trials, known as Phase 4

trials, is to monitor long-term risks and benefits, study different dosage levels or evaluate safety and effectiveness.

In recent years,

the FDA has increased its reliance on these trials.

Phase 4 trials usually involve thousands of participants.

Phase 4 trials also may

be initiated by the company sponsoring the new drug to gain broader market value for an approved drug.

European Regulation .

Similar to the U.S., a European sponsor of a biological product may submit a Marketing Approval Application to the European Medicines

Agency, or EMA, for the registration of the product.

The approval process in Europe consists of several stages, which together are summed

up to 210 days from the time of submission of the application (net, without periods in which the sponsor provides answers to questions

raised by the agency) following which, a Marketing Approval may be granted.

During the approval process, the sponsor’s manufacturing

facilities will be audited in order to assess Good Manufacturing Practice compliance.

The drug approval process

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and may have a material adverse effect on our business, financial condition, results of operations and prospects.

Competition in General

Competition in the area of

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product efficacy, safety, patient convenience, reliability, value and patent position.

Competition for Our

Oral Insulin Capsule

We anticipate the oral insulin

capsule to be a competitive diabetes drug because of its anticipated efficacy and safety profile.

The following are some of the treatment

options for T1D and T2D patients:

Insulin injections,

Insulin pumps, or

A combination of diet, exercise and oral medication which improve the body’s response to insulin or cause the body to produce more insulin.

We anticipated that our oral

insulin capsule would be a competitive diabetes drug because of its anticipated efficacy and safety profile;

however, there are other

treatment options for T1D and T2D patients, such as insulin injections, insulin pumps or a combination of diet, exercise and oral medication

which improve the body’s response to insulin or cause the body to produce more insulin.

Scientific Advisory Board

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Harold Jacob, Dr.

Julio Rosenstock and Dr.

Julio Rosenstock, Dr.

Jay Skyler and Dr.

Roy Eldor , MD,

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years of clinical and scientific experience.

He is currently Director of the Diabetes Unit at the Institute of Endocrinology, Metabolism& Hypertension, Tel-Aviv Sourasky Medical Center.

He is currently Director of the Diabetes Unit at the Institute of Endocrinology, Metabolism

& Hypertension at the Tel-Aviv Sourasky Medical Center.

Prior to that, Dr.

Eldor served as Principal Scientist at Merck Research Laboratories,

Clinical Research–- Diabetes & Endocrinology, Rahway, New Jersey.

He has previously served as a senior physician in internal

medicine at the Diabetes Unit in Hadassah Hebrew University Hospital, Jerusalem, Israel;

and the Diabetes Division at the University of

Texas Health Science Center in San Antonio, Texas (under the guidance of Dr.

Eldor is a recognized expert, with over

50 peer reviewed papers and book chapters, and has been a guest speaker at numerous international forums.

Clinical Research – Diabetes & Endocrinology.

He previously served as a senior physician in internal medicine at the Diabetes

Unit in Hadassah Hebrew University Hospital in Jerusalem, Israel;

and the Diabetes Division at the University of Texas Health Science

Center in San Antonio, Texas.

Eldor is a recognized expert, with over 50 peer reviewed papers and book chapters, and has been a guest

speaker at numerous international forums.

Professor Ele Ferrannini ,

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He is a past President to the European Association for the

Study of Diabetes, which supports scientists, physicians and students from all over the world who are interested in diabetes and related

subjects in Europe, and performs functions similar to that of the ADA in the United States.

Professor Ferrannini has worked with various

institutions including the Department of Clinical & Experimental Medicine, University of Pisa School of Medicine, and CNR (National

Research Council) Institute of Clinical Physiology, Pisa, Italy;

and the Diabetes Division, Department of Medicine, University of Texas

Health Science Center at San Antonio, Texas.

He has also had extensive training in internal medicine and endocrinology, and has specialized

in diabetes studies.

Professor Ferrannini has received a Certificate of the Educational Council for Foreign Medical Graduates from the

University of Bologna, and with cum laude honors completed a subspecialty in Diabetes and Metabolic Diseases at the University of Torino.

He has published over 500 original papers and 50 book chapters and he is a “highly cited researcher,” according to the Institute

for Scientific Information.

Study of Diabetes (EASD), which supports scientists, physicians and students from all over the world who are interested in diabetes and

related subjects in Europe and performs functions similar to that of the American Diabetes Association in the United States.

Ferrannini has worked with various institutions including the Department of Clinical & Experimental Medicine at the University of

Pisa School of Medicine, and CNR (National Research Council) Institute of Clinical Physiology in Pisa, Italy;

and the Diabetes Division,

Department of Medicine at the University of Texas Health Science Center in San Antonio, Texas.

He has extensive training in internal medicine

and endocrinology, and has specialized in diabetes trials.

Professor Ferrannini has received a Certificate of the Educational Council

for Foreign Medical Graduates from the University of Bologna, and completed a subspecialty in Diabetes and Metabolic Diseases at the University

of Torino, cum laude .

He has published over 500 original papers and 50 book chapters and he is a “highly cited researcher,”

according to the Institute for Scientific Information.

Alexander Fleming,

MD an endocrinologist, is Founder and Executive Chairman of Kinexum, a strategic advisory firm.

At the FDA from 1986 to 1998,

he served as a supervisory medical officer in the Division of Metabolism and Endocrine Drug Products and was responsible for landmark

approvals of the first statin, metformin, and other endocrine and metabolic therapies.

He also represented the FDA at the World Health

Organization and on multiple expert working groups of the International Conference on Harmonization (ICH).

Fleming coined the term,

Metabesity, which refers to the constellation of major chronic diseases and the aging process itself, all which share common metabolic

root causes and potential preventive therapies.

He organized the first Congress on Metabesity in London in October 2017, followed by annual

Fleming founded in 2020 the not-for-profit Kitalys Institute as a means of producing Metabesity conferences and advancing

interventions of any kind that can improve health and healthspan.

MD , joined the Oramed Scientific Advisory Board in December 2019.

Fleming, an endocrinologist, is Founder and Executive Chairman

of Kinexum, a strategic advisory firm.

From 1986 to 1998, he served at the FDA as a supervisory medical officer in the Division of Metabolism

and Endocrine Drug Products and was responsible for landmark approvals of the first statin, metformin, and other endocrine and metabolic

He also represented the FDA at the World Health Organization and on multiple expert working groups of the International Conference

on Harmonization (ICH).

Fleming coined the term, Metabesity, which refers to the constellation of major chronic diseases and the aging

process itself, all which share common metabolic root causes and potential preventive therapies.

He organized the first Congress on Metabesity

in London in October 2017, followed by annual conferences.

Fleming founded the non-profit Kitalys Institute as a means of

producing Metabesity conferences and advancing interventions of any kind that can improve health and healthspan.

Professor Avram Hershko,

MD, PhD , joined the Oramed Scientific Advisory Board in July 2008.

He earned his MD degree (1965) and PhD degree (1969) from the

Hebrew University-Hadassah Medical School of Jerusalem.

Professor Hershko served as a physician in the Israel Defense Forces from 1965

After a post-doctoral fellowship with Gordon Tomkins at the University of San Francisco (1969 - 72), he joined the faculty

of the Haifa Technion becoming a professor in 1980.

He is now Distinguished Professor in the Unit of Biochemistry in the B.

Faculty of Medicine of the Technion.

Professor Hershko’s main research interests concern the mechanisms by which cellular proteins

are degraded, a formerly neglected field of study.

Professor Hershko and his colleagues showed that cellular proteins are degraded by

a highly selective proteolytic system.

This system tags proteins for destruction by linkage to a protein called ubiquitin, which had previously

been identified in many tissues, but whose function was previously unknown.

Subsequent work by Professor Hershko and many other laboratories

has shown that the ubiquitin system has a vital role in controlling a wide range of cellular processes, such as the regulation of cell

division, signal transduction and DNA repair.

Professor Hershko was awarded the Nobel Prize in Chemistry (2004) jointly with his former

PhD student Aaron Ciechanover and their colleague Irwin Rose.

His many honors include the Israel Prize for Biochemistry (1994), the Gairdner

Award (1999), the Lasker Prize for Basic Medical Research (2000), the Wolf Prize for Medicine (2001) and the Louisa Gross Horwitz Award

Professor Hershko is a member of the Israel Academy of Sciences (2000) and a Foreign Associate of the U.S.

Academy of Sciences

Professor Hershko served as a physician in the Israel Defense

Forces from 1965 to 1967.

After a post-doctoral fellowship with Gordon Tomkins at the University of San Francisco from 1969 to 1972, he

joined the faculty of the Haifa Technion becoming a professor in 1980.

He is now Distinguished Professor in the Unit of Biochemistry in

Rappaport Faculty of Medicine of the Technion in Haifa, Israel.

Professor Hershko’s main research interests concern the mechanisms

by which cellular proteins are degraded, a formerly neglected field of study.

Professor Hershko and his colleagues showed that cellular

proteins are degraded by a highly selective proteolytic system.

This system tags proteins for destruction by linkage to a protein called

ubiquitin, which had previously been identified in many tissues, but whose function was previously unknown.

Subsequent work by Professor

Hershko and many other laboratories has shown that the ubiquitin system has a vital role in controlling a wide range of cellular processes,

such as the regulation of cell division, signal transduction and DNA repair.

Professor Hershko was awarded the Nobel Prize in Chemistry

in 2004, jointly with his former PhD student Aaron Ciechanover and their colleague Irwin Rose.

His many honors include the Israel Prize

for Biochemistry (1994), the Gairdner Award (1999), the Lasker Prize for Basic Medical Research (2000), the Wolf Prize for Medicine (2001)

and the Louisa Gross Horwitz Award (2001).

Professor Hershko is a member of the Israel Academy of Sciences since 2000 and a Foreign Associate

Academy of Sciences since 2003.

Harold Jacob, MD ,

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Jacob has also served as an attending physician at Hadassah University

Medical Center, where he has served as the director of the gastrointestinal endoscopy unit since September 2013.

Jacob has advised

a spectrum of companies in the past and he served as a consultant and then as the Director of Medical Affairs at Given Imaging Ltd., from

1997 to 2003, a company that developed the first swallowable wireless pill camera for inspection of the intestine.

He has licensed patents

to a number of companies including Kimberly-Clark Corporation.

Medical Center in Jerusalem, Israel, where he has served as the director of the gastrointestinal endoscopy unit since September 2013.

Jacob has advised a spectrum of companies in the past and he served as a consultant and then as the Director of Medical Affairs at

Given Imaging Ltd., from 1997 to 2003, a company that developed the first swallowable wireless pill camera for inspection of the intestine.

He has licensed patents to a number of companies including Kimberly-Clark Corporation.

Since 2014, Dr.

Jacob has served as the Chief Medical Officer and a director

of NanoVibronix, Inc., a medical device company using surface acoustics to prevent catheter acquired infection as well as other applications,

where he served as Chief Executive Officer from 2004 to 2014.

He practiced clinical gastroenterology in New York and served as Chief of

Gastroenterology at St.

John’s Episcopal Hospital and South Nassau Communities Hospital from 1986 to 1995, and was a Clinical Assistant

Professor of Medicine at SUNY from 1983 to 1990.

Jacob founded and served as Editor in Chief of Endoscopy Review and has authored

numerous publications in the field of gastroenterology.

Jacob has served as the Chief Medical

Officer and a director of NanoVibronix, Inc., a medical device company using surface acoustics to prevent catheter acquired infection

as well as other applications, where he served as Chief Executive Officer from 2004 to 2014.

He practiced clinical gastroenterology in

New York and served as Chief of Gastroenterology at St.

John’s Episcopal Hospital and South Nassau Communities Hospital from 1986

to 1995, and was a Clinical Assistant Professor of Medicine at SUNY from 1983 to 1990.

Jacob founded and served as Editor in Chief

of Endoscopy Review and has authored numerous publications in the field of gastroenterology.

Julio Rosenstock,

MD , joined the Oramed Scientific Advisory Board in January 2020.

Rosenstock is Director of the Dallas Diabetes Research Center

at Medical City, and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center, Dallas.

He is board certified

in Internal Medicine, and Endocrinology and Metabolism.

His clinical and research activities have focused on exploring novel agents and

therapeutic strategies to improve glycemic control.

Over the last 30 years, he has participated in hundreds of clinical trials and has

had an active role in the development of new diabetes oral agents, incretin-related therapies and insulin formulations, acting often as

a lead clinical investigator and scientific advisor.

Rosenstock is the Senior Scientific Advisor and Director

of Velocity Clinical Research at Medical City, Dallas, Texas, and a Clinical Professor of Medicine at the University of Texas Southwestern

Medical Center in Dallas, Texas.

He is board certified in Internal Medicine, Endocrinology and Metabolism.

His clinical and research activities

have focused on exploring novel agents and therapeutic strategies to improve glycemic control, particularly early combination therapies

in Type 2 Diabetes.

Over the last 30 years, he has participated in hundreds of clinical trials and has had an active role in the development

of new oral agents, incretin-related therapies and insulin formulations, often acting as a lead clinical investigator and scientific advisor

on the design and reporting of these clinical trials.

Rosenstock has been the author or co-author of 360 peer-reviewed manuscripts

(H-index 105) and several hundred scientific abstracts.

He has also contributed to 13 book chapters on various topics in the field of

He is currently an Associate Editor of Diabetes Care.

( H-index 119 ) and several hundreds of scientific abstracts.

He has also contributed to 13 book chapters on various topics in the

field of diabetes and is considered a key opinion leader in Type 2 Diabetes.

Jay Skyler, MD,

MCAP , joined the Oramed Scientific Advisory Board in January 2020.

Skyler is Professor of Medicine, Pediatrics, & Psychology

in the Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Miami Leonard M.

MCAP, FRCP , joined the Oramed Scientific Advisory Board in January 2020.

Skyler is Professor of Medicine, Pediatrics and Psychology

in the Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Leonard M.

Miller School of Medicine.

He previously held the position of Director of the Division of Endocrinology, Diabetes& Metabolism.

He previously held the position of Director of the Division of Endocrinology, Diabetes and Metabolism.

In addition, Dr.

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Director of Clinical Research and Academic Programs at the Diabetes Research Institute, and an Adjunct Professor of Pediatrics at the

Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver.

Skyler’s research focuses on the clinical aspects

of diabetes, specifically the conduct of randomized controlled clinical trials.

From 1993 until 2015, he was Chairman of the NIH (NIDDK)-sponsored

Diabetes Prevention Trial–- Type 1 (DPT-1) and its successor Type 1 Diabetes TrialNet, a nationwide (and global) network conducting

clinical trials to prevent T1D.

We have been successful in

retaining experienced personnel involved in our research and development program.

In addition, we believe we have successfully recruited

the clinical/regulatory, quality assurance and other personnel needed to advance through clinical studies or have engaged the services

of experts in the field for these requirements.

As of August 31, 2021, we have contracted with thirteen individuals for employment or

consulting arrangements.

Of our staff, five are senior management, four are engaged in research and development work, and the remaining

four are involved in administration work.

Barbara Davis Center for Childhood Diabetes at the University of Colorado in Denver.

Skyler’s research focuses on the clinical

aspects of diabetes, specifically the conduct of randomized controlled clinical trials.

From 1993 to 2015, he was Chairman of the National

Institute of Health (NIDDK)-sponsored Diabetes Prevention Trial–- Type 1 (DPT-1) and its successor Type 1 Diabetes Trial Net, a

nationwide and global network conducting clinical trials to prevent T1D.

Anne Peters, MD ,

joined the Oramed Scientific Advisory Board in June 2022.

Peters is Professor of Medicine at the Keck School of Medicine of the University

of Southern California (USC) and Director of the USC Clinical Diabetes Programs.

Peters earned her medical degree from the Pritzker

School of Medicine at the University of Chicago and performed an internal medicine residency at Stanford University and an endocrinology

fellowship at Cedars-Sinai Medical Center.

She previously directed the clinical diabetes programs at Cedars-Sinai Medical Center and UCLA

in California.

Her research has focused on testing new approaches for diagnosing and treating diabetes and developing systems of care

to improve outcomes in diabetic populations.

Peters is the chair of the Endocrine Society Committee on Diabetes Devices and is on

the EASD/ADA Technology Safety Committee.

Additionally, she is a member of the JDRF Panel on Management of Exercise in type 1 Diabetes

and a member of the ABIM Endocrinology Subspecialty Board.

Peters has consulted for many entities, including the FDA, Optum Rx and

CVS/Caremark to help guide the development and use of treatments for diabetes.

In addition to being an investigator for more than 40 research

Peters has published over 200 articles, has written four books, and has given more than 500 lectures locally, nationally,

and internationally.

She has been on multiple guideline writing committees for the treatment of both type 1 and type 2 diabetes.

a recipient of the ADA Outstanding Physician Clinician Award, the Bernardo Houssay Award from the National Minority Quality Forum and

received a 2021 Endocrine Society Laureate Award for Public Service.

We believe it is imperative

to attract and retain top talent for all positions in the Company.

We seek to make Oramed an inclusive, diverse and safe workplace, with

meaningful compensation, benefits and wellness programs and opportunities.

We have experienced personnel involved in our research and development

programs, as well as appropriate clinical/regulatory, quality assurance and other personnel needed to advance through clinical trials

or have engaged the services of experts in the field for these requirements.

As of December 31, 2022, we have contracted with seventeen

individuals for employment or consulting arrangements, including employees of Oravax.

Of our staff, six are senior management, four are

engaged in research and development work, and the remaining seven are involved in corporate and administration work.

We provide competitive compensation,

health and retirement programs for our employees.

We offer variable pay in the form of bonuses and stock-based compensation for eligible

We also provide our employees with additional benefits such as team-building and educational offsite activities and gym facilities.

We believe that this provides a comprehensive package to engage, motivate and retain our employees as a cohesive unit unified in its goal

to achieve the Company’s strategy and objectives.

Additional Information

Additional information about

us is contained on our Internet website at www.oramed.com.

Information on our website is not incorporated by reference into this report.

On our website, under “Investors”, “SEC Filings”, we make available free of charge our Annual Reports on Form

10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and amendments to those reports filed or furnished pursuant to Section

13(a) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, as soon as reasonably practicable after we electronically

file such material with, or furnish it to, the U.S.

Securities and Exchange Commission, or the SEC.

Reports filed with the SEC are made

available on its website at www.sec.gov.

information about us is contained on our Internet website at www.oramed.com.

Information on our website is not incorporated by reference

into this report.

Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and amendments to those

reports filed or furnished pursuant to Section 13(a) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, are available

free of charge on our website under “SEC Filings” as soon as reasonably practicable after we electronically file such material

with, or furnish it to, the SEC.

Reports filed with the SEC are made available on its website at www.sec.gov and

are also available on the website of the Israeli Securities Authority at www.magna.isa.gov.il or

on the website of the Tel Aviv Stock Exchange at www.tase.co.il.

The following corporate governance documents are also posted on our website:

Code of Ethics,

Whistleblowing Policy and the Charters for each of the Audit Committee, Compensation Committee and Nominating Committee of our Board.

Code of Ethics, Whistleblowing Policy and the charters for each of the Audit Committee, Compensation Committee and Nominating Committee

of our Board.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business