1. For National Priorities: Development and Approval of three Innovative Drugs in China

(1) Rapid development of the anti-COVID-19 drugs Mindvy® (VV116) and Xiannuoxin® (VV934 + Ritonavir)

By integrating key enabling technologies, including high-druggability deuterium modification, prodrug design, and salt screening, the full nonclinical development process for VV116 was completed within 10 months, from design and synthesis to preclinical studies, IND submission, and scale-up production of the API and formulation. Clinical studies showed that oral VV116 significantly shortened time to clinical recovery and reduced viral load, with efficacy non-inferior to Paxlovid and a lower incidence of adverse events. A strong patent strategy was also established and granted rapidly, covering candidate compounds that had advanced to Phase III trials by foreign companies. VV116 became the first deuterium-containing nucleoside drug approved for marketing. In addition, using a proprietary amino acid building-block library, the team innovatively introduced a 1,3-dithiolane spirocyclic motif into small-molecule design and synthesis, creating a strong intellectual property barrier that supported the approval of Xiannuoxin®. Clinical trials demonstrated that Xiannuoxin® effectively shortened disease duration and provided meaningful clinical benefit in patients with risk factors for severe disease.

Mindvy®（民得维®, VV116）

https://simm.cas.cn/web/xwzx/ttxw/202301/t20230130_6602901.html

Xiannuoxin®（先诺欣®, VV934+Ritonavir）

https://simm.cas.cn/web/xwzx/kydt/202301/t20230130_6602892.html

(2) Innovative drug Onvita® (TPN171) approved for erectile dysfunction

Onvita® (TPN171) is a novel, highly potent, and highly selective phosphodiesterase type 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction (ED). Clinical trials demonstrated strong efficacy, a favorable safety profile, and broad applicability across different patient populations and usage scenarios, supporting its position as a potential best-in-class therapy. By improving male reproductive health, this drug contributes to quality of life for patients and their families and may also help address broader social concerns related to declining fertility. TPN171 is also the first domestic drug candidate in China for pulmonary arterial hypertension and has been recognized as a “Highlight Work” by the Chinese Academy of Sciences. It is currently in Phase II clinical trials.

Onvita®（昂伟达®, TPN171）

http://www.simm.ac.cn/web/xwzx/kydt/202507/t20250711_7886926.html

2. Multiple candidates in clinical and preclinical development

(1) Strategic reserve of antiviral candidates and technologies for both routine and urgent public health needs

VV116 has been recognized as a Breakthrough Therapy for the treatment of respiratory syncytial virus (RSV) infection and is currently being evaluated in Phase III clinical trials, with the potential to become the first nucleoside drug approved worldwide for RSV. It has also received clinical trial approval for the treatment of Nipah virus infection.

Using prodrug technologies and nucleoside-specific modification strategies, the team has developed and reserved multiple original broad-spectrum antiviral candidates. VV261 is in Phase I trials for novel bunyavirus infection and has also received clinical trial approval for chikungunya virus infection. VV207, designed for highly pathogenic and highly transmissible DNA viruses such as monkeypox, is currently in preclinical development.

(2) For Reproductive Health, Neuropsychiatric Disorders and Quality of Life, continuously developing new drug candidates

An integrated platform for druggability optimization and evaluation was established, combining phenotypic efficacy with mechanism-based validation. This platform supports drug design based on a high-safety, multi-target synergistic mechanism, as well as structural fine-tuning and multi-target evaluation strategies driven by druggability. The PDE5 inhibitor TPN729 for erectile dysfunction is in Phase III trials. The neurotransmitter modulator VV913 for premature ejaculation is in Phase I trials. The multi-target compound VV027 for female sexual dysfunction is undergoing systematic preclinical research. LV232, the first domestically developed dual-target 5-HTT/5-HT3 antidepressant candidate, offers rapid onset, cognitive improvement, and a low incidence of adverse effects, and has advanced to Phase II trials. TPN102, which has shown significant efficacy in multiple refractory epilepsy models, has entered Phase I trials. The rapid-acting antidepressant candidates VV147 and VV312, targeting NMDA receptors and monoamine transporters, are currently in preclinical development.

3. Innovation platform for green and sustainable API process development via the “Control from Root Design” strategy

Guided by principles of safety, environmental friendliness, simplicity and low consumption, Professor Shen systematically evaluated the green sustainability of chemical reactions and synthetic routes at the earliest stage of technology development, thereby strengthening the competitiveness of downstream process technologies. He has led the development of 23 synthetic routes and process technologies for active pharmaceutical ingredients. The pioneering ‘nitrile hydrolysis’ route for telmisartan has been widely adopted by API manufacturers worldwide. He also rapidly developed a new synthetic route for VV116 based on direct esterification followed by late-stage deuteration, reducing overall production costs by approximately 50 percent; the process was transferred immediately to manufacturing and successfully validated in a single 500 kg batch on the first attempt. He also creatively applied a simultaneous reaction-distillation process to the manufacture of cycloheptatriene, a key intermediate for the anti-monkeypox antiviral API tecovirimat, eliminating the safety risks associated with high-temperature pyrolysis approach and increasing the overall API yield by more than fourfold.

4. Construction of the Belt and Road Joint Laboratory

Representing the Shanghai Institute of Materia Medica, he participated in establishing the CAS Central Asia Center for Drug Research and Development and the Ministry of Science and Technology Belt and Road Joint Laboratory, helping to promote international scientific cooperation, the commercialization of research, and China’s influence in the global biopharmaceutical field. He also contributed to the approval and marketing in Uzbekistan of the innovative drugs MINDVY (VV116, anti-COVID-19) and ONVITA (TPN171, for erectile dysfunction), as well as the antiviral drugs COVFOR (favipiravir tablets), SOVONTA (sofosbuvir tablets), and HEPCLIN (sofosbuvir/velpatasvir tablets).