Oramed Pharmaceuticals Advances Global Commercial Footprint with Oral Insulin Breakthrough and New Filing

In 2016, diabetes giant Novo Nordisk (NYSE: NVO) suddenly announced the cancellation of its oral insulin candidate I338 development program, a decision made shortly after the successful completion of Phase II trials for the insulin pill. Although Novo Nordisk has remained silent on the termination decision, industry speculation suggests that the company was forced to abandon the R&D plan due to the high barriers to drug production and tight financial budgets.

On January 10, 2019, nearly two and a half years after Novo Nordisk terminated its oral insulin development program, the renowned Israeli pharmaceutical company Oramed Pharmaceuticals (TASE: ORMP) announced that it had secured an additional $3 million in funding from Hefei Tianhui Incubation Technologies Co., Ltd. (HTIT). This payment is part of a long-term investment agreement between Oramed Pharmaceuticals and HTIT. Previously, in 2015, HTIT had invested $50 million in Oramed Pharmaceuticals to support the development of its revolutionary flagship product, the oral insulin capsule (ORMD-0801). (For more details, please refer to VCBeat’s coverage.)“Oramed Secures $3 Million in Funding to Develop Oral Insulin Capsules”）

In fact, just one year after Canadian scientists F.G. Banting and C.H. Best discovered insulin in 1921, this protein hormone was already being applied in clinical practice. Three years later, the concept of oral insulin appeared for the first time in professional literature. However, despite the scientific community’s continuous efforts to overcome technical challenges, diabetic patients worldwide still not only engage in a protracted struggle against the disease itself but also contend with the inconvenience and pain associated with insulin injections.

It was not until recent years, as headlines such as “Breakthrough,” “Overcoming the Impossible,” and “First in Humans” gradually began to dominate the medical sections of the media, that the commercialization of oral insulin truly saw the light of day. Among these developments, the most noteworthy has been the progress made by Oramed Pharmaceuticals.

Oramed Pharmaceuticals (NASDAQ: ORMP), founded in 2006 and headquartered in Jerusalem, Israel, was established based on the world-renowned Hadassah University Medical Center, thereby inheriting over 30 years of medical research expertise from its inception.

Hadassah University Medical Center, established in 1934, is a renowned medical institution in Israel founded by Hadassah, the Women’s Zionist Organization of America. As the sixth-largest hospital complex in Israel, it is committed to extending care to all. Hadassah University Medical Center is a tertiary medical center providing specialized and subspecialized treatments. It operates two large hospitals in Ein Kerem and Mount Scopus, with a total of 1,000 beds, 31 operating rooms, and nine specialized intensive care units. The institution employs 5,500 staff members, including 700 physicians and 1,600 nurses.

In addition, Hadassah University Medical Center was nominated for the Nobel Peace Prize in 2005. In 2006, former Israeli Prime Minister Ariel Sharon was hospitalized and treated at Hadassah Hospital following his illness, drawing worldwide attention.

For over two decades, scientists in the Diabetes Unit at Hadassah Hospital, under the leadership of the globally renowned diabetes expert Professor Hanoch Bar-On, have been dedicated to developing a technology that makes oral insulin possible. A medical breakthrough in 2005 laid the foundation for the establishment of Oramed Pharmaceuticals, with researchers from the Hadassah University Medical Center devoting their full efforts to this research. Thus, in the momentous year of 2006, Professor Hanoch Bar-On and Dr. Miriam Kidron co-founded Oramed Pharmaceuticals; it was also in this same year that Professor Hanoch Bar-On passed away.

Logically, the untimely death of a pivotal figure would seem to leave behind the regret of “unfinished business.” However, Professor Hanoch Bar-On not only achieved remarkable accomplishments during his lifetime, but his colleagues have also continued to advance medical technology through Oramed Pharmaceuticals, the company he founded.

Dr. Miriam Kidron, another founder of Oramed Pharmaceuticals, currently serves as a Director and Chief Scientific Officer of the company. Similar to Professor Hanoch Bar-On, this distinguished woman is a pharmacologist and biochemist who has served as a Senior Researcher in the Diabetes Unit at Hadassah University Medical Center for nearly two decades, and she was awarded the Bern Schlanger Prize for her outstanding work in diabetes research. Additionally, Dr. Kidron has been a Visiting Professor at the University of Toronto’s Faculty of Medicine and is a member of the American, European, and Israeli Diabetes Associations.

In contrast, Nadav Kidron, the current Chairman and CEO of Oramed Pharmaceuticals, differs from Professor Hanoch Bar-On and Dr. Miriam Kidron. First, Nadav Kidron is a seasoned entrepreneur who has held executive positions across various companies and multiple industries. He is also a member of the Israel Bar Association and serves on the board of directors of Entera Bio, a joint venture between Oramed Pharmaceuticals and DNA Biomedical Solutions specializing in the biotechnology sector. Furthermore, Nadav Kidron is an international lecturer on Israeli entrepreneurial culture, focusing on the roots of the country as an oasis of innovative ideas.

It can be said that the technology developed by Professor Hanoch Bar-On and his team has been continuously improving. In 2006, the year the company was founded, Oramed Pharmaceuticals announced the launch of its Protein Oral Delivery (POD™) technology, which had undergone more than 30 years of research. Thanks to the relentless efforts of its scientific researchers, Oramed Pharmaceuticals’ technology for converting injectable drugs into oral formulations has become a global leader, establishing the company as a true pioneer in this field.

As a biopharmaceutical company that went public at its inception, Oramed Pharmaceuticals’ core product exemplifies the principle of “accumulating strength over time for a breakthrough.” Backed by more than 30 years of diabetes research, Oramed Pharmaceuticals has enjoyed a relatively smooth fundraising journey since its founding. Its flagship product in clinical development has attracted significant attention from investors, patients with diabetes, and professional researchers alike.

A group of scientists has expressed strong support for Oramed Pharmaceuticals’ technology platform, including prominent figures such as Dr. Michael Berelowitz, former Senior Vice President at Pfizer; Professor John Amatruda, former Senior Vice President at Merck; Professor Ele Ferrannini, former President of the European Association for the Study of Diabetes (EASD); and Professor Avram Hershko, a 2004 Nobel Laureate in Chemistry and a leading authority in drug delivery methods. The Office of the Chief Scientist of Israel has also demonstrated confidence in Oramed’s technology by providing funding for the third consecutive time to support its ongoing research. These endorsements collectively underscore the reliability of Oramed Pharmaceuticals’ technology.

Since its inception, Oramed Pharmaceuticals has been testing its novel technology through various animal and human studies on its two flagship products: the oral insulin capsule ORMD-0801 and the oral exenatide (a GLP-1 analog) capsule ORMD-0901. Furthermore, the combination therapy of these two oral capsules (ORMD-0801 + ORMD-0901) has demonstrated promising results in preclinical trials, with clinical trials expected to follow.

Among these, the oral insulin capsule (ORMD-0801) is the cornerstone of Oramed Pharmaceuticals, serving as the foundation for the company’s new product development. It is currently in Phase II clinical trials, conducted under the supervision of the U.S. Food and Drug Administration (FDA).

Oral Insulin Capsules (ORMD-0801) Are Primarily Targeted at Type 2 Diabetes Mellitus (T2DM).

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by impaired β-cell function and insulin resistance. There are over 340 million patients with T2DM worldwide, imposing an annual economic burden of nearly $50 billion.

According to Oramed Pharmaceuticals, oral insulin is expected to enhance patient medication adherence. Furthermore, orally administered insulin absorbed via the gastrointestinal tract passes through the liver before entering the systemic circulation, thereby mimicking the natural physiological distribution and gradient of endogenous insulin. This innovative therapeutic approach, by enabling early-stage oral insulin administration, has the potential to slow disease progression and delay or even eliminate late-stage complications.

Meanwhile, the oral insulin capsule (ORMD-0801) can also be used as an adjunctive therapy for type 1 diabetes mellitus (T1DM).

Type 1 diabetes, also known as insulin-dependent diabetes mellitus, is an autoimmune disease in which the immune system attacks and destroys pancreatic beta cells. Consequently, patients with type 1 diabetes produce little to no insulin, impairing glucose uptake. Clinically, type 1 diabetes is characterized by fluctuating blood glucose readings and poor glycemic control.

Currently, the oral insulin capsule (ORMD-0801) is expected to serve as an adjunct to insulin injections in the treatment of type 1 diabetes. For unstable, brittle type 1 diabetes, this therapy should enable fewer daily injections and reduce the frequency of blood glucose fluctuations.

According to statistics from the International Diabetes Federation (IDF), there were as many as 425 million diabetes patients aged 20–79 worldwide in 2017, with up to 352 million individuals at risk for type 2 diabetes. The global number of diabetes patients is projected to reach 629 million by 2045. In China, the large population base combined with a continuously rising prevalence rate has led to a rapid increase in the number of diabetes cases. From 2010 to 2017, the number of diabetes patients aged 20–79 in China rose from 43 million to 114 million, and is expected to exceed 150 million by 2045. Meanwhile, the domestic insulin market continues to expand, reaching RMB 57.6 billion in 2018; however, this accounts for only 10% of the global insulin market.

Meanwhile, compared with insulin injection, oral administration holds an irresistible appeal for the patient population, offering benefits such as enhanced patient comfort and medication adherence, reduced risk of infection, simplified application in pediatric care, first-pass metabolism prior to systemic exposure, and cost-effectiveness. These advantages make oral administration the most preferred route of drug delivery. Once the ORMD series of oral formulations truly enters the market, their market penetration potential should not be underestimated.

In early January this year, Oramed Pharmaceuticals secured $3 million in funding from Hefei Tianhui Incubation Technology Co., Ltd. (HTIT) to promote its flagship product, the oral insulin capsule (ORMD-0801), in the Chinese market. This is not its first collaboration with a foreign enterprise. In fact, Oramed Pharmaceuticals’ unique oral delivery technology offers a novel approach to transitioning from currently available injectable therapies to oral administration, prompting pharmaceutical companies of all sizes to seek partnerships with Oramed to assess whether their product pipelines are compatible with its technology. Leveraging its corporate channels, Oramed Pharmaceuticals also facilitates the international market entry of these products.

This includes the Chinese market, with Tianmai Biologics being one of Oramed Pharmaceuticals’ “channel partners,” and it is also the parent company of Hefei Tianhui Incubation Technologies Co., Ltd. (HTIT).

The close relationship between Oramed Pharmaceuticals and Tianmai Biologics dates back to the early stages of its public listing, when Tianmai Biologics’ subsidiary, Hefei Tianhui Incubation Technology Co., Ltd., became one of its shareholders. Furthermore, the two companies entered into a strategic partnership in 2015 focused on their oral insulin product pipelines, jointly establishing a research and development platform for oral drug delivery technologies.

VCBeat (WeChat Official Account: vcbeat) previously conducted an exclusive interview with Tianmai Bio, in which the latter expressed optimism about Oramed Pharmaceuticals’ oral delivery technology. Additionally, considering the substantial market potential post-commercialization, Tianmai Bio has made preparations to build a comprehensive industry chain, ranging from upstream insulin raw material supply to downstream commercial implementation.

“China currently has the world’s largest and most homogeneous population of people with diabetes,” said Nadav Kidron, CEO of Oramed Pharmaceuticals. “We are very pleased to partner with HTIT to bring our oral insulin capsule (ORMD-0801) to this vast market.”

Following Novo Nordisk’s withdrawal from the oral insulin sector, only two companies remain deeply engaged in this field globally: Oramed Pharmaceuticals and Diasome Pharmaceuticals, a biopharmaceutical company based in Ohio, USA. Diasome’s technology utilizes hepatocyte-targeted liposomes to deliver insulin directly to the liver, thereby lowering blood glucose levels by enhancing hepatic glucose uptake.

In addition to Diasome Pharmaceuticals’ hepatocyte-targeting technology, which has already entered clinical trials, researchers at the Massachusetts Institute of Technology (MIT) in the United States leveraged bionic design principles inspired by the balance mechanisms of leopard tortoises to develop a novel device for oral insulin delivery on February 13 this year. Meanwhile, Rani Therapeutics has made progress in the field of robotic capsules, which are poised to become a new vehicle for oral insulin and are currently in the experimental stage. However, compared with Oramed Pharmaceuticals’ established authoritative technology in this domain, recent breakthroughs from the United States have not yet reached a level capable of competing with it.

Moreover, Oramed Pharmaceuticals’ oral insulin is currently undergoing pivotal clinical studies through the FDA regulatory pathway. If successful, the company’s flagship product will become a boon for over 100 million diabetes patients and secure a first-mover advantage in the North American market.

Furthermore, Oramed Pharmaceuticals is striving to maximize the impact of its technological drive. In addition to leveraging Tianmai Bio to enter the Chinese market, the company is expected to soon secure approval for five patents on its technology from the patent offices in Japan, Australia, and New Zealand. This development not only validates Oramed Pharmaceuticals’ technology but also helps establish an international foothold for its oral drug delivery method. Currently, Oramed Pharmaceuticals has 34 additional patents pending, with expectations of further approvals in the future, which is likely to bring about a turnaround in the company’s current financial situation.

Whether from the perspective of ordinary individuals to patients with chronic diseases, or from investors to scientists, the more sensitive humanity becomes to the concepts of “pain” or “convenience,” the more urgent the pursuit of a healthy life becomes. In this arduous journey, the partnership between Oramed Pharmaceuticals and Tianmai Bio may continue to evolve until the technology is refined and ready for market launch. Drug discovery is a significant human endeavor involving three major domains: science, industry, and medical practice. Throughout history, it is evident that exchanges of pharmaceutical knowledge across different countries and cultures have always been key to technological breakthroughs, and such exchanges have typically made indelible contributions to the well-being of all humanity.

Safe and effective medications can not only shorten treatment duration but also conserve various medical resources, carrying significant economic value; oral insulin is undoubtedly a standout in this regard. With healthcare reform imminent in the United States and insulin prices continuing to rise, there is an urgent need for effective therapies among patients and public health systems alike, both domestically and internationally. It is hoped that the day oral insulin becomes available on the market is not too far off.

(Compiled by Ning Chen)