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 Phase 3 oral insulin trial (ORA-D-013-1) 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 ORA-D-013-1
Phase 3 trial data 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, on September 12, 2024 we submitted a protocol for a revised Phase
3 (ORA-D-013-3) clinical trial to the U.S. Food and Drug Administration, or the FDA. We intend to initiate study during 2025. 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.
On
January 22, 2024, we along with our wholly-owned subsidiary Oramed Ltd., entered into a joint venture agreement, or Initial JV Agreement,
with Hefei Tianhui Biotech Co., Ltd. or HTIT, and its subsidiary Technowl Limited or HTIT Sub. OraTech will focus on developing and commercializing
products based on our oral insulin and POD™ technology, utilizing HTIT’s manufacturing capabilities.
On
February 7, 2025, we and HTIT entered into a Joint Venture Agreement, or the JV Agreement, amending the Initial JV Agreement signed on
January 22, 2024. To execute the JV Agreement, we formed OraTech Pharmaceuticals, Inc., or OraTech, which will serve as the joint venture
entity. We currently hold 100% of OraTech shares. OraTech was formed to advance the development and commercialization of oral insulin,
combining our proprietary technology and funding with HTIT’s manufacturing capabilities. Through this partnership, OraTech will
have the technology, resources, and production capacity to bring oral insulin to market. The agreement also outlines the spin-off of
OraTech, or the Spin Off, requiring regulatory filings and the distribution of the majority of OraTech’s shares held by us to our
shareholders. Both we and HTIT agreed to a 120-day lock-up period post-listing, restricting share sales.
The
Initial Closing, set for April 30, 2025, or the Initial Closing, includes an investment of $40,000,000 by HTIT and $7,500,000 by us into
OraTech . Additionally, we will transfer all our intellectual property rights to OraTech. The second closing, contingent on the listing
of OraTech’s shares on Nasdaq, involves a $20,000,000 investment by HTIT and an additional $7,500,000 investment by us, or the
Second Closing. It is expected to close by May 31, 2025, but no later than September 1, 2025. Upon completion of the Initial Closing
and the Second Closing, both HTIT and we will receive OraTech shares, resulting in ownership of 50% for each of HTIT and us, excluding
the impact of the contemplated distribution of OraTech shares to our shareholders.
As
part of the JV Agreement, HTIT will receive $20,000,000 at the Initial Closing and $10,000,000 at the Second Closing under a supply agreement
with OraTech.
1
2023
Scilex Transaction and 2024 Refinancing
2023
Scilex Transaction
On
September 21, 2023, we entered into and consummated transactions, or, collectively, the 2023 Scilex Transaction, with Scilex, pursuant
to which Scilex issued to us:
a.
A senior secured
promissory note, or the Tranche A Note, with a principal amount of $101,875,000, maturing on March 21, 2025 and bearing interest of
SOFR plus 8.5%, payable in-kind. Scheduled principal payments are due on December 21, 2023, March 21, 2024, June 21, 2024, September
21, 2024, and December 21, 2024, with the balance due on March 21, 2025. In January 2025, we extended Tranche A Note maturity from
March 21, 2025 to December 31, 2025. As per the Tranche A Note terms, if the Tranche A Note is not repaid in full on or prior to
March 21, 2024, an exit fee of approximately $3,056,000 was. Since the Tranche A Note was not repaid by March 21, 2024, we are
entitled to the above-mentioned exit fee at the maturity date of the Tranche A Note. As of March 27, 2025, Scilex has repaid
$69,200,000 of the amount due under the Tranche A Note and refinanced $25,000,000 as part of the 2024 Refinancing (as defined
below).
b.
Warrants
to purchase up to 4,500,000 shares of Scilex common stock with an exercise price of $0.01 per share,
or the Closing Penny Warrants, and four additional warrants, or the Subsequent Penny Warrants, each
for 2,125,000 shares of Scilex common stock with an exercise price of $0.01 per share. The Closing
Penny Warrants vested on September 21, 2023, and each of the Subsequent Penny Warrants vested on
each of March 19, 2024, June 17, 2024, September 15, 2024 and December 14, 2024. The Closing Penny
Warrants and the Subsequent Penny Warrants shall become exercisable on the earliest of (i) March
14, 2025 and (ii) the date on which the Tranche A Note has been repaid in full. As of March 27, 2025,
the Closing Penny Warrants and the Subsequent Penny Warrants are fully vested.
On
October 30, 2024, we exercised 4,500,000 Closing Penny Warrants and 2,000,000 Subsequent Penny Warrants that were exercisable at
such time. As a result, we hold 6,500,000 shares of common stock of Scilex.
c.
Transferred warrants, or
the Transferred Warrants, to purchase 4,000,000 shares of Scilex common stock with an exercise price of $11.50 per share, fully exercisable
and expiring on November 10, 2027. On September 20, 2024, we sold the Transferred Warrants for consideration of $300,000 (see below).
As a result, as of March 27, 2025 we do not hold any Transferred Warrants.
On
September 20, 2024, we and Scilex entered into an extension agreement, or the Extension Agreement, to extend the due date of the September
21, 2024 payment under the Tranche A Note. Pursuant to the Extension Agreement, Scilex paid us $2,000,000 on September 23, 2024, which
payment is to be applied as follows: (i) $1,700,000 to the payment due under the Tranche A Note on March 21, 2025 and (ii) $300,000 to
purchase the Transferred Warrants as mentioned above.
2024
Refinancing
On
October 7, 2024, we and certain institutional investors, or the Note B Holders, entered into certain agreements with Scilex, pursuant
to which the Note B Holders purchased in a registered offering, or the 2024 Refinancing, (i) a new tranche B of senior secured convertible
notes of Scilex in the aggregate principal amount of $50,000,000, or the Tranche B Notes, which Tranche B Notes are convertible into
shares of Scilex common stock and (ii) warrants, or the Tranche B Warrants, to purchase up to 7,500,000 shares of Scilex common stock,
or Tranche B Warrants. We purchased 50% of Tranche B Note and Tranche B Warrants and therefore hold an aggregate principal amount of
$25,000,000 under the Tranche B Note and 3,750,000 Tranche B Warrants.
Scilex
received from us, in consideration for our part in Tranche B Notes and the Tranche B Warrants issued to us, an exchange and reduction
of the principal outstanding balance under the Tranche A Note of $22,500,000.
2
Royalty
Purchase Agreement
In
addition, on October 8, 2024, we and certain institutional investors, or the RPA Purchasers, entered into a Purchase and Sale Agreement
or the RPA with Scilex and Scilex Pharmaceuticals Inc., or Scilex Pharma. Pursuant to the RPA, the RPA Purchasers acquired the right
to receive, in the aggregate, 8% of net sales worldwide for 10 years of certain purchase receivables, or the Purchased Receivables with
respect to ZTlido (lidocaine topical system) 1.8%, SP-103 (lidocaine topical system) 5.4%, and any related, improved, successor, replacement
or varying dosage forms of the foregoing. We acquired the right to receive 50% of the Purchased Receivables, as more fully described
in the RPA and therefore hold the right to receive 4% royalties.
In
consideration for our interest in the Purchased Receivables, we exchanged and reduced $2,500,000 of the principal balance under the Tranche
A Note.
Following the refinancing as described above, on October 8, 2024, Scilex
used $12,500,000 of the net proceeds from the proceeds of the Tranche B Note for the repayment of the outstanding balance under the Tranche
A Note.
ZTLido
Rest of the World Binding Agreement
In
addition, on October 8, 2024, we and certain other institutional investors and Scilex entered into a binding term sheet, or the ROW License
Term Sheet, regarding a license and development agreement, or the Lido License Agreement, with respect to services, compositions, products,
dosages and formulations comprising lidocaine, including without limitation, the product and any future product defined as a “Product”
under Scilex Pharma’s existing (i) Product Development Agreement, dated as of May 11, 2011, with Oishi Koseido Co., Ltd., or Oishi,
and Itochu Chemical Frontier Corporation, or Itochu, as amended, and (ii) the associated Commercial Supply Agreement, dated February
16, 2017, between Scilex, Oishi and Itochu, as amended.
Subject
to determination of a final structure for the transactions contemplated by the ROW License Term Sheet, we anticipate that we and such
institutional investors will hold the Lido License Agreement through a joint venture, RoyaltyVest, Inc., or RoyaltyVest.
In
consideration for the rights to be provided under the proposed Lido License Agreement, as more fully described in the ROW License Term
Sheet, (a) RoyaltyVest will invest (whether through cash consideration or in-kind payment through the provision of services) $200,000
per year toward expanding the Product, (b) Scilex will grant RoyaltyVest a worldwide, exclusive right, license and interest to all products
rights for the development, out-licensing, commercialization of any Product outside of the United States and other territories, other
than certain excluded designated territories , or the ROW Territory, and (c) each of RoyaltyVest and Scilex will receive 50% percent
of the net revenue (less expenses) generated from any Product in the ROW Territory. The term sheet is subject to entering into a definitive
agreement (signed on February 22, 2025, see below) and subject to the consent of Oishi and Itochu to the Lido License Agreement.
Tranche
B Note Consent
On January 2, 2025, we and other Tranche B noteholders entered into
deferral and consent agreements with Scilex or the Tranche B Consent, deferring Scilex’s first amortization payment under the Tranche
B Note to October 8, 2026. In consideration, we received approximately $877,000 and 2,500,000 shares of Scilex common stock.
In
addition, as part of the Tranche B Consent and contingent upon certain conditions that were met:
1. Scilex
and the Tranche B Noteholders agreed to a 10-year, assignable 4% royalty on global net sales
of Gloperba and Elyxyb in certain territories outside of the United States , or RoW, of which,
we are entitled to 2% royalties. Gloperba, an oral liquid colchicine formulation for gout,
and Elyxyb, an oral solution for acute migraine treatment, represent key assets in Scilex’s
portfolio. The definitive agreement was signed on February 28, 2025.
2. The
Tranche B Noteholders have the option to fund up to 50% of the cash purchase price for RoW
product rights to Gloperba and Elyxyb (excluding Elyxyb in Canada) and will receive proportional
revenues from commercialization and licensing.
3
Tranche
A Note Maturity Date Extension Amendment
On
January 21, 2025, we entered into an amendment to the Tranche A Note, or the Tranche A Extension Amendment, extending the maturity date
from March 21, 2025, to December 31, 2025 or the Extended Maturity Date. Interest will continue to accrue and be payable on the Extended
Maturity Date. In consideration of the extension, we received 3,250,000 shares of Scilex common stock.
Lidocaine
License Agreement
As
part of the ROW License Term Sheet, on February 22, 2025, we, through its 50% ownership in RoyaltyVest, entered into a license agreement
with Scilex. Under this agreement, RoyaltyVest acquired exclusive rights to develop, manufacture, and commercialize lidocaine-based products,
including ZTlido (lidocaine topical system 1.8%) and SP-103, in the ROW Territory. As part of the arrangement, RoyaltyVest and Scilex
will each receive 50% of the net profits from the commercialization of these products. Given our 50% ownership in RoyaltyVest, we effectively
holds a 25% in the profits generated under this agreement.
BioXcel
In order to diversify our investments as a part of our use of cash
strategy, on
March 4, 2025, we participated in a registered direct offering by BioXcel Therapeutics, Inc. (Nasdaq: BTAI), or BioXcel, acquiring 2,000,000
shares of BioXcel’s common stock and accompanying warrants to purchase up to an additional 2,000,000 shares. The shares and warrants
were purchased at a combined offering price of $3.50 per share and warrant, representing 50% of the total 4,000,000 shares issued in
the offering. The warrants have an exercise price of $4.20 per share, are immediately exercisable, and will expire five years from the
date of issuance.
BioXcel
is a biopharmaceutical company leveraging artificial intelligence to develop innovative medicines in neuroscience and immuno-oncology.
Its lead programs focus on treatments for agitation in neuropsychiatric disorders and other central nervous system conditions.
As of March 27, 2025, we have sold 869,992 shares and continues to
hold 1,130,008 shares of BioXcel common stock.
Real Estate Transactions
Additionally, as a part of
our cash management strategy, we have engaged in certain real estate transactions.
In January 2025, we
entered into an agreement to acquire a parcel of land in Mevaseret Zion, Israel for a total purchase price of NIS 5,800,000
(approximately $1,586,000). The transaction is structured in installments, and as of March 27, 2025, we have paid approximately $1,210,000
toward the acquisition price. Under the agreement, the developer is responsible for executing all development-related activities,
and we and the developer will share the profits upon the future sale of the property.
On March 24, 2025, we
entered into a loan agreement to finance a purchase of a real estate asset in Jerusalem, Israel in the amount of $22,650,000. The
loan has a one-year maturity and is secured by a first-ranking mortgage on a property valued at approximately $800,000,000,
providing significant collateral coverage. The loan bears an annual interest rate of 12%.
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, on September 12, 2024 we submitted a protocol for a revised Phase 3 (ORA-D-013-3) clinical
trial to the FDA. We intend to initiate this study during 2025. 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.
4
Joint
Venture Agreement : As mentioned above, on February 7, 2025, we entered into JV Agreement with HTIT. The collaboration combines our
POD technology with HTIT’s manufacturing capabilities, creating a synergy. This integration of technology and manufacturing expertise
will enable us to ensure consistent, high-quality production at scale, setting new standards for oral protein delivery.
OraTech
is backed by a substantial capital and operational commitment. These resources support the initiation of a Phase 3 clinical trial in
the U.S. As mentioned above, by leveraging insights from prior clinical studies, we have strategically designed this refined Phase 3
trial to focus on key patient subpopulations that we believe have the highest potential to demonstrate efficacy.
Oral
Vaccine
On
March 18, 2021, we entered into a 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.
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.
Impact
of Current Events
On October 7, 2023, the State of Israel was attacked by Hamas, a group
designated as a terrorist organization by the United States, and the State of Israel subsequently declared war on Hamas. Since that time,
Israel has been engaged in a multi-front armed conflict with combatants located in Gaza, the West Bank, Syria, Iran, Lebanon and Yemen.
The situation in the region remains volatile and the possibility of renewed conflicts persist. As of March 27, 2025, 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.”
Real
Estate Investments
On November 7, 2024, our Board of Directors, or the Board, approved
investments of up to $10,000,000 in real estate assets. This decision aligns with our strategic approach to capital allocation, leveraging
opportunities in the current real estate market where we have identified attractive investment prospects. With interest rates expected
to decline and valuations presenting favorable entry points, the Board believes these investments could provide long-term value appreciation
and potential income streams, further strengthening our financial position. As we continues to evaluate our business strategy, including
potential structural changes, these investments are intended to enhance financial flexibility and maximize shareholder value. On February
13, 2025, the Board approved increasing the real estate investments to up to $30,000,000.
Diabetes
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, approximately 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. According to the American Diabetes Association, or ADA, in 2023, the United States there
were approximately 37 million people with diabetes. Diabetes is a leading cause of blindness, kidney failure, heart attack, stroke and
amputation.
5
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 26 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 140 patents, eight of which were issued during the year ended December 31, 2024, 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, 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.
6
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, 2024, Entera had not paid any royalties to Oramed Ltd. During the years
ended December 31, 2024 and 2023, we did not sell any of DNA’s ordinary shares. As of December 31, 2024, we held approximately
1.4% of DNA’s outstanding ordinary shares and approximately 0.3% 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 $37,500,000, of which $3,000,000 was payable immediately,
$8,000,000 will be paid subject to our entry into certain agreements with certain third parties, and $26,500,000 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, 2024, we received aggregate milestone payments of $20,500,000 out of the aggregate amount of $37,500,000.
On
August 21, 2020, we received a letter from HTIT, disputing certain pending payment obligations of HTIT under the TLA.
Pursuant
to the terms of the JV Agreement, each of us, HTIT and HTIT Sub, irrevocably released and waived (i) any claims and demands against each
other party in connection with the TLA; and (ii) all rights, obligations and liabilities set out and arising with respect to the performance
of the TLA.
HTIT
has submitted a Marketing Authorization Application to China’s regulators for the oral insulin capsule in China. Since the TLA was novated
to OraTech, OraTech is expected to receive royalties from any future sales in China
7
Oravax
License
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
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 $25,000,000 to $100,000,000, 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 $1,500,000. Akers Biosciences
Inc. contributed $1,500,000 in cash to Oravax and a license agreement to the Oravax product.
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 $15,000,000 in developmental
milestones, $2,000,000 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. This agreement was assigned to OraTech.
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.
8
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.
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.
9
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.
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.
10
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 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 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. 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.
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.
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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.
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.
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.
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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, 2024, we have contracted with thirteen individuals for employment or consulting arrangements. Of our staff, four are
senior management, three 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.