UBiENCE Destroys Two Proteins at Once, Could Beat Traditional Cancer Drugs

OIST Innovation and Lifetime Ventures co-host Startup Elevate on September 29-30, 2025, at the Okinawa Institute of Science and Technology (OIST). This article features some of the startups that participated in this deep tech startup showcase event.

The field of targeted protein degradation (TPD) has rapidly emerged as one of the most promising innovative technologies in the global pharmaceutical industry. Leading this transformation with their proprietary SNIPER technology—which surpasses conventional PROTAC (Proteolysis Targeting Chimera) approaches—is UBiENCE, a company dedicated to developing treatments for challenging diseases including cancer and pulmonary fibrosis.

Founded in 2018, UBiENCE aims to commercialize the world’s first bifunctional protein degradation-inducing drugs, building upon research conducted by Dr. Mikihiko Naito, Project Professor at the University of Tokyo. The company operates with a lean three-person executive team: CEO Yasuhiro Iwata (medicinal chemistry specialist), CPO Nobuyuki Takahashi (pharmacology specialist), and Founder / CFO Hirobumi Takeuchi (pictured above, business development and general management), all working together to drive efficient fabless-model research and development.

The global TPD market is experiencing rapid growth, with the first PROTAC drug (Vepdegestrant, developed by Arvinas) reaching the regulatory filing stage in 2025, marking the industry’s entry into the commercialization phase. However, as limitations of conventional PROTAC technology become apparent, UBiENCE’s SNIPER technology demonstrates a revolutionary approach of “simultaneously degrading two proteins with a single drug,” charting a pathway toward next-generation standard treatments.

Proprietary Bifunctional Technology

Traditional drug discovery approaches have relied on “inhibiting” the function of disease-causing proteins to achieve therapeutic effects. However, this methodology faces limitations including drug resistance development and challenges targeting “undruggable” proteins—those lacking appropriate pocket structures for conventional small-molecule drugs to bind effectively.

This led to the emergence of TPD drugs based on the revolutionary concept of “degrading” disease-causing proteins within cells. This technology leverages the cellular ubiquitin-proteasome system (the cell’s protein quality control mechanism) to selectively degrade target proteins.

The drug discovery concept of selectively degrading disease-causing proteins emerged around 2000, but was not technically established until the 2010s. Previously, we achieved therapeutic effects by inhibiting target protein function, but actually degrading and removing the proteins themselves was extremely difficult. What we’re developing represents a completely different therapeutic approach. (Takeuchi)

PROTACs are bifunctional molecules that link target proteins with E3 ubiquitin ligases (enzymes that attach ubiquitin, the degradation signal, to proteins). They consist of a target protein-binding domain connected via a chemical linker to an E3 ligase-binding domain. When this molecule brings the target protein and E3 ligase into proximity within cells, ubiquitin is transferred to the target protein, marking it for proteasomal degradation.

UBiENCE’s SNIPER (Specific and Nongenetic IAP-dependent Protein Eraser) technology features a Two-hand effect (bifunctionality that simultaneously degrades two proteins, like grasping two objects with both hands) that surpasses conventional PROTAC technology. While typical PROTACs only degrade target proteins, SNIPER simultaneously degrades both target proteins and disease-specifically overexpressed IAPs (Inhibitor of Apoptosis Proteins). Apoptosis refers to the mechanism by which predetermined cells undergo programmed death. High expression of IAPs inhibits apoptosis, thereby activating tumors. Due to this mechanism, various pharmaceutical companies have previously worked on IAP inhibitors.

When companies develop PROTACs targeting specific proteins, they typically use industry-standard E3 ligases such as CRBN (cereblon) and VHL (von Hippel-Lindau protein). While this approach can degrade target proteins, it fails to degrade other disease-related proteins. This represents a fundamental limitation of targeting only one protein at a time. (Takeuchi)

In contrast, UBiENCE’s IAP ligands (compounds that bind to apoptosis inhibitor proteins) can degrade both target proteins and IAPs. This dual mechanism of action enables approaches to complete disease elimination that conventional therapeutics struggle to achieve. In cancer cell proliferation inhibition experiments, while typical approaches show approximately 80% inhibitory effects, SNIPER technology achieves over 90% inhibition.

Cancer cells are extremely difficult to inhibit in terms of proliferation. If even 5% remain, they will proliferate again. Moreover, this proliferation leads to further mutations, creating risks that existing drugs become ineffective. Therefore, achieving near-complete suppression is particularly crucial. In cancer treatment, even minimal residual cells cannot be tolerated. (Takeuchi)

SNIPER’s technological advantages extend to overcoming drug resistance. Conventional inhibitors require binding to specific sites (active sites) on target proteins, losing effectiveness when mutations change the “key-hole shape.” However, SNIPER can induce ubiquitination (degradation marking) as long as it connects anywhere on the target protein, potentially addressing resistance acquisition through mutations depending on the compound structure.

Grand View Research’s industry analysis indicates that PROTAC-like chimera approaches account for approximately 50% of the field, with diverse technological approaches including molecular glue degraders competing in the space. Molecular glues are small molecules that directly link target proteins with E3 ligases—unlike PROTACs’ bifunctional design, they induce degradation through single molecules. However, UBiENCE’s SNIPER technology represents an extremely rare bifunctional approach, establishing the company’s unique technological domain.

From a pharmacokinetic perspective, SNIPER demonstrates superior characteristics. Conventional inhibitors face “dose-dependency” issues requiring high drug concentrations due to limited target protein binding sites. SNIPER’s efficient protein degradation enables high therapeutic effects even at low doses, allowing safer and more effective treatments while reducing patient burden.

Fabless Operations and Strategic Partnerships

UBiENCE has maintained extremely lean organizational operations since its founding. Operating with a three-director structure as a fabless startup (a business model focused on R&D without manufacturing facilities), the company minimizes fixed costs through disciplined management. R&D operations are outsourced to Contract Research Organizations (CROs) in India, establishing a global framework from an early stage.

The balance of the three executives’ expertise proves optimal. Iwata’s chemical expertise enables design and synthesis of proprietary IAP ligands, while Takahashi’s pharmacological knowledge allows biological verification and optimization of SNIPER technology’s bifunctionality. Takeuchi’s business oversight facilitates smooth global strategic partnership development and fundraising.

Drawing from extensive experience in drug discovery venture management, Takeuchi served as CEO of TSE-listed biotech company RaQualia Pharma from 2021 to 2024, where he led the acquisition of FIMECS, a protein degradation drug developer. This proven track record in business development and M&A transactions directly contributes to UBiENCE’s strategic growth initiatives.

The current pipeline consists of four disease-specific projects. The most advanced is an IPF-targeted therapeutic being accelerated through collaboration with D. Western Therapeutics Institute (DWTI).

Regarding strategic partnership development across pipelines, Takeuchi cites risk hedging and expertise utilization. While joint project execution provides cost-sharing benefits for risk distribution, the primary advantage lies in partnering with specialists to complement technical capabilities and knowledge in areas beyond the company’s internal capacity.

Therapeutic area-specific expertise becomes particularly crucial from a specialization perspective. The company’s pipeline includes ophthalmology, which Takeuchi identifies as extremely specialized.

The eye is a specialized organ with unique immune systems and pharmacokinetics unlike other organs. Additionally, neglecting these diseases causes clearly visible impacts on quality of life—blindness, for example. Because they directly affect daily life, the safety and efficacy requirements differ from drugs in other therapeutic areas. This necessitates partnerships with specialists possessing relevant expertise.

Considering such drug discovery complexities, Takeuchi emphasizes the necessity of strategies premised on collaboration with other pharmaceutical companies. Collaborative research approaches create important credibility as partnership track records, benefiting future fundraising and business development. Particularly considering combination therapy importance in cancer treatment, synergistic effects through partnerships with existing partner company drugs can be anticipated.

Japanese Drug Discovery Startups facing Challenges

For global expansion, UBiENCE emphasizes early-stage relationship building. Drug discovery startups typically face lengthy paths to licensing deals, with successful cases requiring long-term communication. For example, the partnership between Eli Lilly and PeptiDream required approximately eight years from initial contact to final contract execution.

Throughout such extended relationship-building processes, UBiENCE emphasizes strategic approaches understanding partner characteristics and corporate cultures. Particularly important is addressing differences in business development approaches between Western pharmaceutical companies and Japanese enterprises. Western companies often reflect technology acquisition achievements more significantly in performance evaluations compared to Japanese companies, with specialized Business Development personnel continuously exploring technology acquisition opportunities through sustained information exchange.

Conversely, Japanese companies sometimes experience friction between open innovation departments actively pursuing external technology licensing and research departments dedicated to internal technology development. To avoid such friction, it is necessary to understand partner needs and create mutually beneficial partnerships that demonstrate synergy. The key lies in adapting collaboration approaches to partner characteristics. For Japanese companies, collaborative research and parallel development may facilitate better internal understanding.

International expansion also emphasizes information dissemination through academic conferences and industry events. The company implements multifaceted approaches covering research, business development, and finance through participation in overseas TPD (targeted protein degradation) conferences—Annual TPD & Induced Proximity Summit (Boston, USA), TPD & Induced Proximity Summit Europe (London, UK), and JP Morgan Healthcare Conference (San Francisco, USA).

However, in pursuing such global expansion, Japanese drug discovery startups face structural domestic regulatory constraints. Takeuchi identifies structural problems surrounding Japanese drug discovery startup environments. While improvements are evident in seed creation environments, serious challenges exist at social implementation stages. Major problems include the following:

1. Insufficient funding for basic research: While other countries have significantly increased research funding, Japan’s “selection and concentration” policy has resulted in uneven distribution and insufficient academic research funding. Basic patents often have narrow scopes and may not meet sufficient standards, frequently failing to meet major pharmaceutical companies’ requirements. Naturally, this makes it difficult for drug discovery startups to scale, undermining Japanese intellectual property’s international competitiveness.
   
2. Lack of public support for practical implementation stages like safety testing: Primarily concerning academia-originated seeds, the underlying assumption is that cell toxicity and safety evaluations should be private enterprise responsibilities, and existing research funding often fails to provide sufficient data. From the perspective of independent academic drug discovery, Japan lacks subsidy systems for this stage—a policy gap. Fortunately, continuous efforts by academic researchers have maintained basic research capabilities without decline. If Japan aims to pursue academic drug discovery, comprehensive support is urgently needed.
   
3. Structural defects in IPO systems: While the US biotech IPO market fluctuates significantly with market conditions—reaching over 100 companies in favorable years (143 companies in 2021, according to EY’s Beyond Borders report)—Japan saw only four IPOs in 2024, representing an extreme disparity. The US enables IPOs within approximately six months with the shortest review period, while Japan requires unqualified audit opinions for the most recent two fiscal periods and the most recent quarterly report, realistically requiring a minimum of three years.
   
   The fundraising environment leading to IPO also differs significantly. In the US, cases of going public after Series H (8th funding round) or I (9th round) are common, with many companies obtaining PoC (Proof of Concept: initial demonstration of drug efficacy) internally. In contrast, Japanese companies often go public at Series C through E (3rd-5th rounds), with licensing partners obtaining PoC or licensing occurring at even earlier stages.
   
   These differences result in substantial NPV (net present value: current value of future profits) disparities. Naturally, valuations increase more when companies advance internal development. In a sense, US investors and analysts are more selective, but the environment supports this approach. While VCs and startups in Japan are moving in this direction, supportive policies and infrastructure development are urgently needed.
   
4. Overlooked individual investor protection issues: Most listed Japanese biotech companies are supported by individual investors, but they easily become targets for margin trading (trading using borrowed funds or stocks from securities companies) by institutional investors with abundant capital and sophisticated trading techniques.
   
   This results in short-term stock price manipulation unrelated to business performance and excessive volatility, hampering appropriate stock price formation based on companies’ intrinsic values. Such market environments not only reduce individual investors’ incentives for long-term holdings but also prevent drug discovery startups from securing necessary funding and concentrating on long-term R&D.

This creates structural problems hindering healthy enterprise development. Potential solutions include margin trading restrictions for companies with going concern uncertainties, though such measures remain unaddressed due to concerns about restricting institutional investors’ trading freedom and protecting their interests.

Targeting Commercialization in the 2030s

According to UBiENCE’s development roadmap, their most advanced IPF therapeutic targets late-2030s commercialization. Currently in lead optimization (primary compound optimization), the program will subsequently undergo three phases (Phase Ⅰ, Phase Ⅱ, and Phase Ⅲ clinical trials) before approval, anticipating approximately ten years total development time.

While drug discovery startups ideally handle final commercialization independently, clinical trials through manufacturing and sales require hundreds of billions of yen and sophisticated expertise. Considering funding and time constraints, licensing out (granting usage permissions for internally developed technologies and patents to major pharmaceutical companies) represents the realistic approach.

Additionally, cancer treatment rarely achieves cures through single agents, with combination therapies using multiple drugs becoming standard. In oncology, mutual benefits arise from strategic partnerships through synergistic effects combining with partner companies’ existing drugs, providing patients with effective combination treatment options.

Regarding technological development directions, the company plans target expansion beyond current four-pipeline projects. This includes more precise treatments leveraging cancer-specific E3 ligases and expansion beyond protein degradation technology into antibody-drug conjugates (ADCs: novel therapeutics combining antibodies with drugs). By leveraging SNIPER’s IAP ligand technology, synergistic effects through combination with ADCs can be anticipated.

For future market development, the company anticipates technological coexistence rather than competition with existing PROTAC technologies. Takeuchi envisions optimal technology selection based on disease and target protein characteristics, with SNIPER technology serving disease areas requiring stronger therapeutic effects while existing PROTAC technology handles cases where simple protein degradation suffices.

Regarding fundraising, the company currently operates at seed stage, actively pursuing investments from VCs (venture capitalists) and corporate investors. To enhance investor appeal, they strategically utilize public exposure through events like StartupElevate, effectively communicating technological advantages and market opportunities.

UBiENCE’s challenges extend beyond mere technology development, potentially driving paradigm shifts across the entire pharmaceutical industry. The transition from conventional “inhibition” to “degradation” and from single targets to “dual targets” represents a revolutionary approach providing new therapeutic options for overcoming drug resistance and achieving complete remission.

Particularly significant is the capability to address targets previously considered undruggable (medical demand for diseases lacking effective treatments). The company’s dual-target degradation mechanism adopts a completely novel approach that enables drug development for targets impossible or insufficiently treatable through conventional drug discovery.Supporting such technological innovation is the rapidly growing targeted protein degradation market.

Toward 2030s commercialization, UBiENCE’s pioneering next-generation drug discovery revolution will bring new hope to patients worldwide suffering from intractable diseases including cancer and fibrosis. The company’s commitment to technological innovation demonstrates new possibilities for Japan’s biotechnology industry within the global pharmaceutical sector.