Item 1. Business
ITEM
1. BUSINESS.
Description
of Business
We
are 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.
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.
On
January 11, 2023, we announced that the ORA-D-013-1 Phase 3 trial did not meet its primary or secondary endpoints. As a result, we terminated
this trial and a parallel Phase 3, ORA-D-013-2 clinical trial. In 2023, we completed an analysis of the data from the ORA-D-013-1 Phase
3 trial and found that subpopulations of patients with pooled specific parameters, such as body mass index, or BMI, baseline HbA1c and
age, responded well to oral insulin. Based on this analysis, we are working on a protocol for a new Phase 3 clinical trial to be submitted
to the FDA. We are additionally examining our existing pipeline and have commenced an evaluation process of potential strategic opportunities,
with the goal of enhancing value for our stockholders.
Scilex
Transaction
On
August 7, 2023, we entered into a Stock Purchase Agreement, as subsequently amended on August 9, 2023 and August 21, 2023, or the Sorrento
SPA, with Sorrento Therapeutics, Inc., or Sorrento, to acquire certain equity securities of Scilex owned by Sorrento, or the Purchased
Securities, for a purchase price of $105 million. Sorrento and its affiliated debtor, Scintilla Pharmaceuticals, Inc., or Scintilla and
together with Sorrento, the Debtors, are in Chapter 11 bankruptcy proceedings.
On
August 9, 2023, we entered into a Senior Secured, Super-Priority Debtor-in-Possession Loan and Security Agreement, or the Senior DIP
Loan Agreement, with the Debtors in the principal amount of $100 million, which included a non-refundable closing fee of $450,000 paid
in full out of the proceeds. This amount was subsequently drawn in full by the Debtors and was intended to be used by us as a credit
for the consideration for the Purchased Securities, with an additional $5,000,000 in cash to be paid by us at closing. Thereafter, we
and Sorrento continued discussions and negotiations relating to the sale contemplated under the Sorrento SPA.
Securities
Purchase Agreement
On
September 21, 2023, or the Closing Date, we entered into and consummated the transactions, or, collectively, the Transaction, contemplated
by a Securities Purchase Agreement, or the Scilex SPA, with Scilex and Acquiom Agency Services LLC. Pursuant to the Scilex SPA, in exchange
for Scilex assuming Sorrento’s outstanding obligations under the Senior DIP Loan Agreement, or the DIP Assumption, and for the
ability to credit the amounts assumed under the DIP Assumption in exchange for certain equity securities of Scilex owned by Sorrento,
Scilex (i) issued to us (A) a Senior Secured Promissory Note due 18 months from the date of issuance in the principal amount of $101,875,000,
or the Note, which includes accrued and unpaid interest of $875,000 under the Senior DIP Loan Agreement and $1,000,000 of fees added
to the principal amount of the Note, (B) a warrant to purchase up to an aggregate of 4,500,000 shares of common stock of Scilex, par
value $0.0001 per share, or the Scilex Common Stock, and containing certain restrictions on exercisability, or the Closing Penny Warrant,
and (C) warrants to purchase up to an aggregate of 8,500,000 shares of Scilex Common Stock, or the Subsequent Penny Warrants, and, together
with the Closing Penny Warrant, the Penny Warrants, each with an exercise price of $0.01 per share and each with certain restrictions
on exercisability, and (ii) caused certain outstanding warrants to purchase up to an aggregate of 4,000,000 shares of Scilex Common Stock
with an exercise price of $11.50 per share to be transferred to us, or the Transferred Warrants and together with the Penny Warrants,
the Warrants. In addition, on the Closing Date, Scilex reimbursed $1,910,000 of the Company’s Transaction expenses pursuant to
the Scilex SPA.
Pursuant
to the terms of the Scilex SPA, Scilex agreed to certain restrictions on additional issuances of equity securities. In connection with
the Transaction, we and Sorrento mutually agreed to terminate the Sorrento SPA and to release all claims we and Sorrento may have against
one another, and Scilex completed the acquisition of the Purchased Securities.
1
Senior
Secured Promissory Note
The
Note matures on March 21, 2025 or upon an uncured event of default, subject to certain mandatory prepayments, and bears interest at a
rate per annum equal to Term SOFR (as defined in the Note) plus 8.5% (subject to a Term SOFR floor of 4.0%), to be paid in-kind, by being
capitalized and added to the principal amount of the Note on a monthly basis. The Scilex SPA provides for principal payments of (i) $5
million on December 21, 2023, (ii) $15 million on March 21, 2024, and (iii) $20 million on each of June 21, 2024, September 21, 2024,
and December 21, 2024, and for the entire remaining principal balance of the Note to be paid on March 21, 2025. If the Note is not repaid
in full on or prior to March 21, 2024, an exit fee equal to $3,056,250 shall be payable upon repayment of the Note in full.
The
Note constitutes senior secured indebtedness of Scilex and is guaranteed by all existing or future formed, direct and indirect, domestic
subsidiaries of Scilex and is secured by a first priority security interest in and liens on all of the assets of Scilex, subject to customary
and mutually agreed permitted liens and except for certain specified exemptions.
Mandatory
prepayments under the Note are required following the earlier of (a) April 1, 2024 and (b) the date upon which certain of Scilex’s
outstanding indebtedness is repaid in full. Voluntary prepayments may be made at Scilex’s discretion; provided that, if made prior
to the one-year anniversary of the Closing Date, Scilex will also be required to pay a customary 50% interest make-whole on the portion
of the Note so prepaid.
The
Note includes customary events of default, upon which the Note will bear interest at a default rate of Term SOFR plus 15.0%, which shall
be payable in-kind, by being capitalized and added to the principal amount of the Note on a monthly basis. If the Note is accelerated
upon an event of default, Scilex is required to repay the principal amount of the Note at a mandatory default rate of 125% of such principal
amount (together with 100% of accrued and unpaid interest thereon and all other amounts due in respect of the Note).
Until
the obligations under the Note are repaid in full, we have the right to designate one non-voting observer, to attend meetings of the
board of directors and committees of Scilex and its subsidiaries. Currently, David Silberman, our Chief Financial Officer, is the observer.
Pursuant
to the terms of the Scilex SPA, we received the first principal payment of $5 million on December 21, 2023. The next principal payment
in the amount of $15 million is expected to be paid on March 21, 2024.
Warrants
The
Closing Penny Warrant will be exercisable upon the earliest of (i) March 14, 2025, (ii) the date on which the Note has been repaid in
full and (iii) the Management Sale Trigger Date (as defined therein), if any, and will expire on the date that is the fifth anniversary
of the issuance date. For purposes of the Closing Penny Warrant (as well as the Subsequent Penny Warrants), the Management Sale Trigger
Date is generally the first date that either Dr. Henry Ji, Scilex’s Executive Chairperson, or Mr. Jaisim Shah, Scilex’s Chief
Executive Officer and President and a member of Scilex’s Board of Directors, engages in certain sales or other similar transfers
of shares of Scilex Common Stock or other of Scilex’s or any of its subsidiaries’ securities, subject to certain exceptions
as are customary for lock-up agreements executed by directors and officers in connection with financings or similar transactions. The
exercise price of the Closing Penny Warrant is $0.01 per share, subject to adjustment.
We
were issued four Subsequent Penny Warrants, each for 2,125,000 shares of Scilex Common Stock, which shall vest and become exercisable
on the date that is the later of (i) March 19, 2024, June 17, 2024, September 15, 2024 or December 14, 2024, respectively, or the Subsequent
Penny Warrant Vesting Date, and (ii) the earliest of (A) March 14, 2025, (B) the date on which the Note has been repaid in full and (C)
the Management Sale Trigger Date (as defined therein), if any. Each Subsequent Penny Warrant will expire on the date that is the fifth
anniversary of the issuance date; provided that, if the Note is repaid in full prior to the Subsequent Penny Warrant Vesting Date applicable
to such Subsequent Penny Warrant, such Subsequent Penny Warrant will expire on the date the Note is repaid in full. We may exercise the
Penny Warrants by means of a “cashless exercise.”
The
Penny Warrants may not be exercised if we, together with our affiliates, would beneficially own in excess of 9.9% of the number of shares
of Scilex Common Stock outstanding immediately after giving effect to such exercise; provided, that we may increase or decrease such
limitation upon 61 days’ prior notice to Scilex.
The
Transferred Warrants are listed on the Nasdaq Capital Market, or Nasdaq, have an exercise price of $11.50 per share, are fully exercisable,
and expire on November 10, 2027.
2
Registration
Rights Agreement
In
connection with the Scilex SPA, on September 21, 2023, we entered into a registration rights agreement with Scilex, pursuant to which
Scilex granted us certain registration rights applicable to the resale of the shares underlying the Warrants and agreed to pay liquidated
damages equal to the product of 2.0% multiplied by the sum of (x) the aggregate principal amount outstanding under the Note and (y) the
aggregate Exercise Price (as defined in the Closing Penny Warrant) of the Closing (capped at 12%) of the aggregate subscription amount.
Research
and Development
Oral
Insulin
Type
2 Diabetes : We 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 or 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 2023, we completed an analysis of the data from the ORA-D-013-1 Phase
3 trial and found that subpopulations of patients with pooled specific parameters, such as BMI, baseline HbA1c and age, responded well
to oral insulin. These subsets exhibited an over 1% placebo adjusted, statistically significant, reduction in HbA1c. Based on this analysis,
we are working on a protocol for a new Phase 3 clinical trial to be submitted to the FDA.
Joint
Venture Agreement : On January 22, 2024, Oramed and its wholly-owned subsidiary, Oramed Ltd., entered into a Joint Venture Agreement,
or the JV Agreement, with HTIT Biotech and Technowl Limited, a wholly-owned indirect subsidiary of HTIT Biotech, or HTIT Sub, and together
with HTIT Biotech, HTIT, pursuant to which, subject to the terms and conditions set forth in the JV Agreement, the parties will establish
a joint venture, or the JV, based on Oramed’s oral drug delivery technology.
The
JV will focus on the development and worldwide commercialization of innovative products based on Oramed’s oral insulin and POD™
(Protein Oral Delivery) pipeline and HTIT’s manufacturing capabilities and technologies. The parties intend for the JV to use the
protocol we are currently working on to initiate a Phase 3 oral insulin trial in the United States.
Oramed
and HTIT will initially hold equal shares in the JV, with each owning 50% of the equity. The board of directors will initially consist
of equal representation from HTIT and Oramed. HTIT will contribute to the JV $70 million in cash, while Oramed will contribute $20 million
(comprised of $10 million in cash and $10 million in shares of Oramed common stock that will be subject to certain registration rights)
and will transfer intellectual property related to its oral insulin and POD™ technology, as well as other assets in the Oramed
pipeline. HTIT will have an option to invest additional funds into the JV up to an aggregate amount of $20 million, thereby increasing
its equity holdings and board representation. Oramed will be entitled to receive a 3% royalty on gross revenues of the JV generated from
Oramed related assets.
The
consummation of the JV Agreement is subject to and contingent upon the parties entering into additional agreements within a three-month
period, including an asset transfer agreement for the transfer of Oramed’s intellectual property to the JV, a commercial supply
agreement for the manufacture and supply of products by HTIT to the JV, as well as other documents and agreements to regulate the relationship
of the parties and the JV to be formed pursuant to the JV Agreement. There is no assurance that the parties will complete and sign these
additional agreements within the agreed timeline or at all. If such agreements are not signed within the agreed timeframe, then either
party may apply a 30-day extension, after which the JV Agreement may be terminated and voided by either party. Thereafter, the consummation
of the JV transaction is further subject to the satisfaction or waiver of certain other closing conditions within a three-month period
following the completion of the aforesaid ancillary agreements. If the closing conditions are not met within the agreed timeframe, then
either party may apply a 30-day extension, after which the JV Agreement may be terminated and voided by either party. In addition, completion
of the transactions contemplated under the JV Agreement is subject to the satisfaction or waiver of customary and certain other closing
conditions.
NASH :
On September 13, 2022, we reported positive top line results from a double blind, placebo controlled clinical trial of ORMD-0801 for
the treatment of non-alcoholic steatohepatitis, or NASH, in T2D, 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. The trial also evaluated
the effectiveness of ORMD-0801 in reducing liver fat content over the 12-week treatment period by observing several independent measures.
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.
3
Oral
Vaccine
On
March 18, 2021, we entered into a license agreement, or the Oravax License Agreement, with Oravax, a 63% owned joint venture to commercialize
oral vaccines for COVID-19 and other novel coronaviruses based on Premas Biotech Pvt. Ltd.’s proprietary vaccine technology involving
a triple antigen virus like particle, or the Oravax product.
In
October 2022, Oravax reported positive preliminary Phase 1 data for Cohort A of a Phase 1 clinical trial, meeting primary or 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 virus like particle vaccine antigens observed in the majority of the patients dosed, and no safety
issues were observed, including mild symptoms. Cohort B completed dosing in January 2023. Cohort B measured Immunoglobulin G, or IGG,
against the spike (S) protein, showing positive IGG in approximately 55% of the patients dosed. We are currently evaluating our path
forward for Oravax’s oral vaccines for COVID-19.
PeriTech
Acquisition and License
In
December 2023, we executed and completed an agreement with PeriTech Pharma Ltd., or PeriTech, acquiring the rights to their film-forming
technology tailored for the delivery of topical/dermatology agents. This includes a once-daily over-the-counter treatment for hemorrhoids.
The PeriTech pipeline extends its potential applications to include indications such as pruritus ani, anal warts, anal fissures and herpes
labialis.
We
have entered into an exclusive licensing agreement with Genomma Lab Internacional S.A.B. de C.V, or Genomma Labs, pursuant to which we
granted Genomma Labs the development and commercialization rights to the PeriTech pipeline, in exchange for a royalty based on net sales.
Impact
of Current Events
On
October 7, 2023, the State of Israel was attacked by and subsequently declared war on Hamas. Israel has been in an ongoing
state of war with Hamas since that time. Following the attack by Hamas, Hezbollah has also launched attacks against Israel and Israel
has been responding to these attacks with targeted air strikes. It is possible that other terrorist organizations, including Palestinian
military organizations in the West Bank, as well as other hostile countries, such as Iran, will join the hostilities. As of March 6,
2024, we believe that there is no immediate risk to our business operations related to these events. For further information, see “Item
1A. Risk Factors,” under “We are affected by the political, economic and military risks of having operations in Israel.”
Raw
Materials
Our
oral insulin capsule for clinical trials was manufactured by Fidelio Healthcare, a diversified European Contract Development and Manufacturing
Organization (CDMO) in the pharmaceutical and healthcare industries.
In
July 2010, 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
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
Diabetes
is a disease in which the body does not produce or properly use insulin. Insulin is a hormone that causes sugar to be absorbed into cells,
where the sugar is converted into energy needed for daily life. The cause of diabetes is attributed both to genetics (type 1 diabetes,
or T1D) and, most often, to environmental factors such as obesity and lack of exercise (T2D). According to the International Diabetes
Federation, or IDF, an estimated 537 million adults (20-79 years) worldwide suffered from diabetes in 2021 and the IDF projects this
number will increase to 783 million by 2045. Also, according to the IDF, in 2021, an estimated 6.7 million people died from diabetes.
According to the American Diabetes Association, or ADA, in the United States there were approximately 37.3 million people with diabetes,
or 11.3% of the United States population in 2019. Diabetes is a leading cause of blindness, kidney failure, heart attack, stroke and
amputation.
4
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
maintain a proactive intellectual property strategy, which includes patent filings in multiple jurisdictions, including the United States
and other commercially significant markets. We hold 38 patent applications currently pending, with respect to various compositions, methods
of production and oral administration of proteins and exenatide. Expiration dates for pending patents, if granted, will fall between
2026 and 2039.
We
hold 117 patents, eight of which were issued during the fiscal year ended December 31, 2023, 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, Brazilian and Japanese patent offices
that cover part of our technology for the oral delivery of exenatide; and patents issued by the European, Austrian, Belgian, Denmark,
French, German, Irish, Italian, Luxembourg, Monaco, Netherlands, Norway, Spanish, Swedish, Swiss, U.K. and Japanese patent offices for
treating diabetes.
Consistent
with our strategy to seek protection in key markets worldwide, we have been and will continue to pursue the patent applications and corresponding
foreign counterparts of such applications. We believe that our success will depend on our ability to obtain patent protection for our
intellectual property.
Our
patent strategy is as follows:
● 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.
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 and unpatentable know-how that we seek to protect, in part, by confidentiality agreements. Our policy is to
require our employees, consultants, contractors, manufacturers, outside scientific collaborators and sponsored researchers, Board of
Directors, or 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.
5
Out-Licensed
Technology
Entera
Bio
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, Oramed Ltd. 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, 2023, 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. During the years ended December 31, 2023 and 2022, we did not sell any of DNA’s ordinary shares.
As of December 31, 2023, we held approximately 1.4% of DNA’s outstanding ordinary shares and approximately 0.4% of Entera’s
outstanding ordinary shares.
HTIT
On
November 30, 2015, we entered into a Technology License Agreement, or TLA, with 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 Agreement. 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 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. 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, 2023, we received aggregate milestone payments of $20.5 million out of the aggregate amount of $37.5 million.
On
August 21, 2020, we received a letter from HTIT, disputing certain pending payment obligations of HTIT under the TLA. We wholly disputed
said claims and are planning to resolve any such claims as part of our discussions with HTIT.
See
“—Research and Development” above regarding the JV Agreement we signed with HTIT to establish the JV, based on Oramed’s
oral drug delivery technology. The proposed JV will focus on the development and worldwide commercialization of innovative products based
on Oramed’s oral insulin and POD™ (Protein Oral Delivery) pipeline and HTIT’s manufacturing capabilities and technologies.
Oravax
License
In
consideration for the grant 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, of which two members will be appointed by us, that will oversee the ongoing research, development, clinical
and regulatory activity with respect to the Oravax product. In addition, we agreed to buy and Oravax agreed to issue to us 1,890,000
shares of common stock of Oravax, representing 63% of the common stock of Oravax for the aggregate amount of $1.5 million. Akers Biosciences
Inc. contributed $1.5 million in cash to Oravax and a license agreement to the Oravax product.
6
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 were received by Oramed in 2022, and up to 15% royalties on gross sales. Medicox will also be responsible
for gaining regulatory approval in the Republic of Korea.
Government
Regulation
The
Drug Development Process
Regulatory
requirements for the approval of new drugs vary from one country to another. In order to obtain approval to market our drug portfolio,
we need to go through a different regulatory process in each country in which we apply for such approval. In some cases, information
gathered during the approval process in one country can be used as supporting information for the approval process in another country.
As a strategic decision, we decided to first explore the FDA regulatory pathway. The following is a summary of the FDA’s requirements.
The
FDA requires that pharmaceutical and certain other therapeutic products undergo significant clinical experimentation and clinical testing
prior to their marketing or introduction to the general public. Clinical testing, known as clinical trials or clinical studies, is either
conducted internally by life science, pharmaceutical or biotechnology companies or is conducted on behalf of these companies by CROs.
The
process of conducting 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 trials are conducted, as well as describe a number of the parties involved in these
trials.
Protocols .
Before commencing human clinical trials, the sponsor of a new drug or therapeutic product must submit an IND application to the FDA.
The application contains, among other documents, what is known in the industry as a protocol. A protocol is the blueprint for each drug
study. The protocol sets forth, among other things, the following:
● Who
must be recruited as qualified participants,
● How
often to administer the drug or product,
● What
tests to perform on the participants, and
● What
dosage of the drug or amount of the product to give to the participants.
Institutional
Review Board . 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. The institutional review board does not report
to the FDA, but its records are audited by the FDA. Its members are not appointed by the FDA. 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
trials. It approves 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 trials.
Clinical
Trials . Human clinical trials or testing of a potential product are generally done in three stages known as Phase 1 through Phase
3 testing. The names of the phases are derived from the regulations of the FDA. Generally, there are multiple trials conducted in each
phase.
Phase
1 . 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. Phase 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.
7
Phase
2 . 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 . Phase 3 trials involve testing large numbers of participants, typically several hundred to several thousand persons. The purpose
is to verify effectiveness and long-term safety on a large scale. These trials generally last two to three years. Phase 3 trials are
conducted at multiple locations or sites. 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 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. market.
Phase
4 . The FDA may 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 is time-consuming, involves substantial expenditures of resources, and depends upon a number of factors, including
the severity of the illness in question, the availability of alternative treatments, and the risks and benefits demonstrated in the clinical
trials.
Other
Regulations
Various
federal, state and local laws, regulations, and recommendations relating to safe working conditions, laboratory practices, the experimental
use of animals, the environment and the purchase, storage, movement, import, export, use, and disposal of hazardous or potentially hazardous
substances, including radioactive compounds and infectious disease agents, used in connection with our research are applicable to our
activities. They include, among others, the U.S. Atomic Energy Act, the Clean Air Act, the Clean Water Act, the Occupational Safety and
Health Act, the National Environmental Policy Act, the Toxic Substances Control Act, and Resources Conservation and Recovery Act, national
restrictions on technology transfer, import, export, and customs regulations, and other present and possible future local, state, or
federal regulation. The compliance with these and other laws, regulations and recommendations can be time-consuming and involve substantial
costs. In addition, the extent of governmental regulation which might result from future legislation or administrative action cannot
be accurately predicted and may have a material adverse effect on our business, financial condition, results of operations and prospects.
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Competition
Competition
in the area of biomedical and pharmaceutical research and development is intense and significantly depends on scientific and technological
factors. These factors include the availability of patent and other protection for technology and products, the ability to commercialize
technological developments and the ability to obtain regulatory approval for testing, manufacturing and marketing. Our competitors include
major pharmaceutical, medical products, chemical and specialized biotechnology companies, many of which have financial, technical and
marketing resources significantly greater than ours. In addition, many biotechnology companies have formed collaborations with large,
established companies to support research, development and commercialization of products that may be competitive with ours. Academic
institutions, governmental agencies and other public and private research organizations are also conducting research activities and seeking
patent protection and may commercialize products on their own or through joint ventures. We are aware of certain other products manufactured
or under development by competitors that are used for the treatment of the diseases and health conditions that we have targeted for product
development. We can provide no assurance that developments by others will not render our technology obsolete or noncompetitive, that
we will be able to keep pace with new technological developments or that our technology will be able to supplant established products
and methodologies in the therapeutic areas that are targeted by us. The foregoing factors could have a material adverse effect on our
business, prospects, financial condition and results of operations. These companies, as well as academic institutions, governmental agencies
and private research organizations, also compete with us in recruiting and retaining highly qualified scientific personnel and consultants.
Competition
within our sector is increasing, so we will encounter competition from existing firms that offer competitive solutions in diabetes treatment
solutions. These competitive companies could develop products that are superior to, or have greater market acceptance, than the products
being developed by us. We will have to compete against other biotechnology and pharmaceutical companies with greater market recognition
and greater financial, marketing and other resources.
Our
competition will be determined in part by the potential indications for which our technology is developed and ultimately approved by
regulatory authorities. In addition, the first product to reach the market in a therapeutic or preventive area is often at a significant
competitive advantage relative to later entrants to the market. Accordingly, the relative speed with which we, or our potential corporate
partners, can develop products, complete the clinical trials and approval processes and supply commercial quantities of the products
to the market are expected to be important competitive factors. Our competitive position will also depend on our ability to attract and
retain qualified scientific and other personnel, develop effective proprietary products, develop and implement production and marketing
plans, obtain and maintain patent protection and secure adequate capital resources. We expect our technology, if approved for sale, to
compete primarily on the basis of product efficacy, safety, patient convenience, reliability, value and patent position.
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
We
maintain a Scientific Advisory Board consisting of internationally recognized scientists who advise us on scientific and technical aspects
of our business. The Scientific Advisory Board meets periodically to review specific projects and to assess the value of new technologies
and developments to us. In addition, individual members of the Scientific Advisory Board meet with us periodically to provide advice
in their particular areas of expertise. The Scientific Advisory Board consists of the following members, information with respect to
whom is set forth below: Dr. Roy Eldor, Professor Ele Ferrannini, Dr. Alexander Fleming, Professor Avram Hershko, Dr. Harold Jacob, Dr.
Julio Rosenstock, Dr. Jay Skyler and Dr. Anne Peters.
Dr.
Roy Eldor , MD, PhD , joined the Oramed Scientific Advisory Board in July 2016. He is an endocrinologist, internist and
researcher with over twenty years of clinical and scientific experience. 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. 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. 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.
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Professor
Ele Ferrannini , MD , joined the Oramed Scientific Advisory Board in February 2007. He is a past President to the European
Association for the 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. Professor 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.
Dr.
Alexander Fleming, MD , joined the Oramed Scientific Advisory Board in December 2019. Dr. 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 therapies. He also represented the FDA at the World Health Organization and on multiple expert working
groups of the International Conference on Harmonization (ICH). Dr. 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. In 2020, Dr. 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. 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 the B. 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 of the U.S. Academy of Sciences since 2003.
Dr.
Harold Jacob, MD , joined the Oramed Scientific Advisory Board in November 2016. Since 1998, Dr. Jacob has served as the president
of Medical Instrument Development Inc., a company which provides a range of support and consulting services to start-up and early stage
companies as well as patenting its own proprietary medical devices. Since 2011, Dr. Jacob has also served as an attending physician at
Hadassah University Medical Center in Jerusalem, Israel, where he has served as the director of the gastrointestinal endoscopy unit since
September 2013. Dr. 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. Dr. Jacob founded and served
as Editor in Chief of Endoscopy Review and has authored numerous publications in the field of gastroenterology.
Dr.
Julio Rosenstock, MD , joined the Oramed Scientific Advisory Board in January 2020. Dr. 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. Dr. Rosenstock has been the author or co-author of 386 peer-reviewed
manuscripts ( H-index 124 ) and several hundreds of scientific abstracts and he is considered a key opinion leader in Type 2 Diabetes.
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.
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Dr.
Jay Skyler, MD, MCAP, FRCP , joined the Oramed Scientific Advisory Board in January 2020. Dr. 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 and Metabolism.
In addition, Dr. Skyler is Deputy 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 at the University of Colorado in Denver. Dr. 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.
Dr.
Anne Peters, MD , joined the Oramed Scientific Advisory Board in June 2022. Dr. 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. Dr. 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 under-resourced populations. Dr. Peters has consulted for many
entities, including the FDA, the Centers for Disease Control and Prevention and the National Institutes of Health to help guide the development
and use of treatments for diabetes. In addition to being an investigator for more than 40 research studies, Dr. 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. She was a recipient of the ADA Outstanding
Physician Clinician Award, the Bernardo Houssay Award from the National Minority Quality Forum and received an Endocrine Society Laureate
Award for Public Service.
Employees
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, 2023, we have contracted with fifteen individuals for employment or consulting arrangements, including employees of
Oravax. Of our staff, five are senior management, four are engaged in research and development work, and the remaining six 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 employees. 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. 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.
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