The Billion-Dollar Molecule’s Next Chapter: Innovator Behind Risen Bio’s 8-Year Bootstrapped Journey Files IPO

This year marks the ninth year since Professor Cheng Jiawei, a scientist from Vertex Pharmaceuticals, led Raythea Bio into the development of first-in-class new drugs.

At a time when the domestic market was dominated by generic drugs, the probability of successfully developing a first-in-class (FIC) innovative drug was merely one in 100,000. Nevertheless, Cheng Jiawei and Ruiser chose the path of “innovation” and “risk-taking.”

Over its nine-year development, Ruiser Bio has not followed the conventional path of innovative pharmaceutical companies but has instead charted a unique course: its lead product was developed outside China’s five mainstream regulatory and research systems, the company has never engaged in external financing since its inception, and its drug’s first indicated indication directly targets pancreatic cancer, known as the “king of cancers.”

Today, Ruiser Bio’s first innovative drug for the treatment of pancreatic cancer has received Orphan Drug Designation from the U.S. FDA and entered the clinical trial phase, marking a milestone achievement in its innovative drug pipeline laid out a decade ago.

Behind Reith’s unconventional path lie three pivotal decisions made by Cheng Jiawei and the founding team of Reith Biopharmaceuticals.

At the age of 29, Cheng Jiawei earned his Ph.D. from the University of Washington, becoming the fastest physical chemistry doctoral graduate in the university’s history of over a century by completing his degree in less than four years. His first job after graduation was as a research and development scientist at Vertex Pharmaceuticals, which is now widely renowned.

At that time, Vertex was still a small company with only dozens of employees, yet it had assembled a group of outstanding scientists. Its founder, Joshua Boger, hailed as the “Harvard Genius” and the “Prince of the Pharmaceutical Industry,” led an elite team that had never previously brought a new drug to market. Within three years, he took Vertex public and developed a molecule generating annual sales exceeding $1 billion. Today, Vertex boasts a market capitalization of $63.1 billion, firmly securing its place among the top 30 pharmaceutical companies worldwide and emerging as a phenomenal dark horse in the industry.

The key to Vertex’s rise to fame lay in its subversion of traditional pharmaceutical paradigms. In the 1990s, drug research and development were relatively backward; many pharmaceutical companies preferred to focus on minor modifications of existing drugs rather than investing in new drug discovery. However, from its inception, Vertex was dedicated to creating novel therapeutics. This adventurous spirit, unbound by the constraints of traditional pharmaceutical firms, profoundly influenced Cheng Jiawei’s entrepreneurial philosophy.“We must independently develop new drugs in the future.”The seed took root in his heart.

However, the path of innovation is exceptionally arduous. During his tenure at Vertex Pharmaceuticals, Jiawei Cheng endured the darkest hours marked by the failure of the flagship FK-506 development project and the company’s near-collapse, and he also witnessed how the HIV protease inhibitor VX-478 brought the company back from the brink.

These experiences reinforced his inner conviction:The risks of developing new drugs are enormous, but taking these risks is worthwhile because the rewards from innovation are equally substantial.

From the laboratory to Wall Street, Vertex’s “fascinating adventure story” was later chronicled in the book *A Billion-Dollar Molecule*, which has become essential reading for pharmaceutical entrepreneurs seeking to understand the modern medical revolution.

But Cheng Jiawei’s adventure story has only just begun.

After working at Vertex for two years, Cheng Chia-wei returned to National Tsing Hua University in Taiwan as an associate professor and, a few years later, became the youngest full professor on campus at that time. Today, one-third of the university’s technical patents in the field of biomedicine are his inventions, earning him the reputation among industry insiders as a “genius” in innovative drug research and development. In 2002, when Taiwanese policy began allowing university professors to establish biotechnology companies externally while retaining their on-campus laboratories and faculty positions, Cheng embarked on his entrepreneurial journey.

Over the seven years since leaving academia, Cheng Jiawei successfully grew a biotechnology startup from inception to its listing on a Canadian stock exchange. Along the way, he forged many valuable friendships, including with Zhou Jianwei, Co-Founder and General Manager of Ruise Biologics. Sharing a common vision on “the strategic direction for innovative pharmaceutical companies,” Cheng Jiawei has once again embarked on the journey of novel drug development.

And this time,Vertex’s “innovation” and “risk-taking spirit” have been replicated at Resilience Bio.Since 2006, traditional pharmaceutical companies in China have continued to focus primarily on chemical drugs and generics, with very few enterprises engaged in the research and development of innovative biologics—a sector that was largely viewed unfavorably by industry insiders.

However, Raythe Biotech has set its sights on developing first-in-class biopharmaceuticals.

“Innovation” and “a spirit of adventure” have been consistent themes throughout Cheng Jiawei’s entrepreneurial journey, playing a pivotal role in the three key decisions he made after founding Raythor Biologics. The most challenging of these was the decision to go eight years without raising any external financing.

After 2015, domestic biopharmaceutical startups in China began to spring up like mushrooms after rain, ushering in successive waves of investment fervor and propelling the Chinese biopharmaceutical industry into a golden age of development that was the envy of all.

For Rese Bio, founded in 2013, holding multiple patents, adhering to source innovation, and developing first-in-class (FIC) innovative drugs, its substantial core advantages make the “financing-to-IPO” path a perfectly natural choice. However, “we do not wish to hype up the concept of innovative drugs; there are too few companies truly dedicated to the meticulous R&D of innovative medicines.” This is the consensus reached by Zhou Jianwei and Cheng Jiawei.

The partnership between Zhou Jianwei and Cheng Jiawei is clearly defined: one handles external resource integration, while the other oversees internal product development. Many scientist-entrepreneurs face a common challenge—balancing the need for focused scientific research with the demands of engaging various stakeholders. When excessive time and energy are diverted to these external interactions, it becomes impossible to maintain the focus required for product development.

This is also a profound insight from Cheng Jiawei’s entrepreneurial journey. Through the experience of taking his first company public, he came to understand the dual positive and negative pressures that capital exerts on the development of a biopharmaceutical company.

In Cheng Jiawei’s view, if investors with aligned philosophies are not secured, the pursuit of returns by capital may divert the R&D pace—originally controlled by scientists—onto a different trajectory. Therefore, finding a balance between capital interests and R&D progress is particularly critical.

In the early days of Ruise Biopharma, as it was developing entirely original drugs with no precedents to reference, everything remained unknown. Consequently, Ruise Biopharma’s R&D team always proceeded step by step, making extensive preparations for each foundational research project. However, from an outsider’s perspective,"Eight years of dedicated, grounded R&D work is particularly precious."

The ability to persevere for eight years stems from the unwavering commitment and investment of Ruise Biologics’ shareholders. Having personally witnessed the suffering endured by their friends and family members in the late stages of cancer, they are even more determined to see Ruise Biologics’ products transition from scientific research to commercialization, thereby benefiting a broader patient population.

Throughout this process, Raythe Biology did receive acquisition offers from large pharmaceutical companies and faced the lure of capital financing, but Cheng Jiawei remained steadfast in his convictions and unmoved.“Maintaining our own R&D pace and truly benefiting patients is what matters most.”

Nowadays, the uncertainty surrounding R&D is gradually dissipating. Reser Bio has gained a clearer understanding and greater control over its products and clinical performance, and its development roadmap has become largely defined. Cheng Jiawei believes it is time to initiate external fundraising. With a firm grasp of product R&D progress, the company will carefully consider how to deliver strong returns to investors and safeguard their interests in the next phase.

Another critical decision lay in the selection of indications for its flagship product, RP-72. This time, however, Ruise demonstrated a prudent and pragmatic R&D strategy.

June 2019,Raythera Biologics’ Core Product RP-72 Receives U.S. FDA Orphan Drug Designation for Pancreatic Cancer Treatment, marking a significant milestone in the company's development.

RP-72 is the world’s first IL-8-targeted anti-tumor protein therapeutic developed to modulate the tumor microenvironment., with CXCR1/2 as its target. Composed of natural amino acids, it undergoes natural metabolism in vivo and inhibits tumor growth and metastasis by modulating immune homeostasis within the tumor microenvironment of solid tumors.

Pancreatic cancer is a highly aggressive malignancy with a very poor prognosis and relative insensitivity to chemotherapy. For patients undergoing first-line chemotherapy, the median survival from treatment initiation to therapeutic failure is only 3.7 months.

When asked why pancreatic cancer was chosen as the first indication, Cheng Jiawei stated that this was a carefully considered R&D strategy for the company: “If we can achieve favorable efficacy in treating pancreatic cancer, a notoriously challenging disease, we will have greater confidence in expanding to the treatment of other solid tumors.”

Currently, numerous anticancer drugs have been approved for market launch; however, there are few medications specifically targeting patients with advanced-stage cancer, leaving them as a population with limited therapeutic options. RP-72, as a broad-spectrum anticancer agent, has demonstrated promising therapeutic efficacy in clinical trials involving patients with advanced cancer. Nevertheless, clinical trials entail substantial financial investment from pharmaceutical companies. Raythea Biosciences seeks to identify a pathway that can both expedite regulatory approval and demonstrate drug efficacy, thereby providing treatment solutions to patients in need as soon as possible. This pathway is obtaining Orphan Drug Designation from the U.S. Food and Drug Administration (FDA).

Obtaining orphan drug designation means that the number of patients required for clinical trials will be significantly lower than that for cancers with large patient populations. Once efficacy is demonstrated, the next phase of clinical trials can be advanced rapidly. Furthermore, after securing orphan drug designation in the United States and achieving success in clinical trials, a drug may qualify for the FDA’s Breakthrough Therapy Designation, which can substantially shorten the clinical development timeline. This provides a significant boost to the drug’s approval and market launch.

“After conquering pancreatic cancer, we will proceed with broader development and application for other cancer types.”"Cheng Jiawei said."

Currently, Ruisai Biotech’s flagship products are RP-72 and RP-15, both of which are novel, original anti-tumor biologics. Among them, RP-72 is the most advanced, having entered Phase I clinical trials in the United States, while RP-15 remains in preclinical development.

Selecting RP-72 as the company’s flagship anti-cancer product was underpinned by a tortuous journey from its inception to validation. This experience also corroborates what Cheng Jiawei has consistently emphasized,“Drug Development Truly Based on Clinical Needs”。

RP-72 was initially developed primarily for lung injury. The 2003 SARS outbreak increased the demand for treatments for acute lung injury. However, after the SARS epidemic ended, the development of RP-72 was discontinued.

The turning point emerged during Cheng Jiawei’s academic research on cancer therapy, as the anticancer potential of RP-72 gradually came to light. Upon entering clinical trials, the efficacy of RP-72 was validated, and the quality of life during survival was significantly improved.

Witnessing the improvement in patients who had previously exhausted all therapeutic options, Cheng Jiawei and the founding team resolved to bring the drug to market, leveraging the most rigorous scientific approaches to drug development to meet patients’ treatment needs.

Robust clinical data are key to validating drug efficacy. During the Phase I clinical trial, RP-72 primarily targeted pancreatic cancer patients who had undergone first-line chemotherapy. Its safety has been scientifically validated to a certain extent: the first dose caused no toxic side effects in three patients, two of whom showed improved conditions with effects lasting over two months. RP-72 has now entered the second dose escalation stage. With dose safety assured, Raythe Biotech will proceed to validate the safety of combination therapy.

Currently,Only Three Cancer Drugs That Alter the Tumor Microenvironment Have Entered Clinical Trials Worldwide, both antagonists and monoclonal antibody drugs are in the R&D pipeline. Major pharmaceutical companies such as BMS and AstraZeneca have already invested heavily in this therapeutic area. Notably, BMS has combined this therapy with its PD-1 inhibitor Opdivo and launched Phase II clinical trials across eight different cancer types.

Meanwhile, RP-72 aims to obtain clinical trial approval from China’s National Medical Products Administration (NMPA) in the first half of 2023, enabling the direct initiation of Phase II clinical studies for pancreatic cancer and the launch of investigator-initiated trials (IITs) across multiple cancer types in collaboration with major hospitals such as Beijing 301 Hospital. Ruiser also hopes to conduct joint research projects with the National Health Commission to promote the expansion of this drug’s indications.

Another drug, RP-15, is an oncolytic peptide (ACP) therapeutic developed by Rayther Biologics using its PDC drug development platform. It works by injecting oncolytic peptides into solid tumors to induce tumor destruction and release antigens, thereby guiding the patient’s immune system to recognize and kill cancer cells. Preclinical animal studies have demonstrated significant efficacy.

Although currently there are only two product pipelines, Ruisai Biotech is not worried, especially with RP-72 as its flagship product, due to its ability toCore Advantages of Combination Therapy, it can not only penetrate the market by combining with chemotherapy and radiotherapy drugs as well as other targeted therapies, but also expand into other therapeutic areas, thereby deriving more drugs with therapeutic potential through continuous combination and development.

Raythor Bio’s innovative adventure story will continue.