About Taiwan Liposome Company

Taiwan Liposome Company, Ltd., a clinical-stage specialty pharmaceutical company, engages in the development and commercialization of novel nanomedicines that combine its proprietary lipid-assembled drug delivery platform with approved active pharmaceutical ingredients (APIs). TLC599 The company’s primary product candidate, TLC599, is an intraarticular, or in-joint, injectable BioSeizer formulation of the API steroid dexamethasone sodium phosphate (DSP). With Phase II data demonstrating statistically significant pain reductions through 24 weeks, the company focuses TLC599 has the potential to become a treatment for the management of osteoarthritis (OA) pain. It has completed an open-label Phase I/II clinical trial of various patients with knee OA. Patients were randomized to be treated with a single dose of TLC599 at a dose level of either 6mg or 12mg DSP, and then followed up for 12 weeks with the primary efficacy endpoint to assess pain. The company has also completed a double-blind, placebo-controlled Phase II clinical trial in various patients to evaluate the effects of TLC599 at two different dose levels at multiple time points over a 24-week period. The company completed an end-of-Phase II meeting with the Food and Drug Administration (FDA) in April 2019 and initiated a pivotal Phase III trial called ‘EXCELLENCE’ in October 2019 evaluating the safety and efficacy of single and repeat administrations of TLC599 for the purpose of the company New Drug Application submission. It dosed various patients in EXCELLENCE with the first injection of TLC599, active comparator or placebo in January 2021, and focuses to have dosed all eligible patients with the second injection by July 2021. TLC590 The company’s second product candidate, TLC590, is a non-opioid, BioSeizer formulation of the API ropivacaine and is in development for post-surgical pain management. A two-part Phase II clinical trial of TLC590 in patients following bunionectomy was completed in May 2020. The safety, dose linearity and relative bioavailability were established in Part 1 in June 2019. TLC399 The company’s third product candidate, TLC399, is a multilamellar (multilayered) and multivesicular (membrane enclosed sacs) BioSeizer formulation of DSP for ophthalmology indications. The company designed TLC399 to have effects when injected into the eye’s vitreous humor to treat macular edema associated with retinal vein occlusion (RVO). The company has completed conduct of a randomized, double-blind Phase II clinical trial evaluating three different doses of TLC399 in RVO patients and is in the process of preparing the final data report. As of December 31, 2020, in clinical and animal studies conducted, the company had observed potential sustained duration of action of three to six months. The company focuses exploring additional ophthalmic indications for TLC399 alone or in combination with intravitreal anti-vascular endothelial growth factor drugs, such as diabetic macular edema, an indication where other steroid products have previously demonstrated efficacy. TLC178 The company’s fourth product candidate, TLC178, which uses its NanoX targeted delivery technology with vinorelbine tartrate as the API, is under development to treat RMS, a form of soft tissue sarcoma (STS) that frequently occurs in children. The company has received a Rare Pediatric Disease Designation for TLC178 in rhabdomyosarcoma (RMS), which would qualify TLC178 in this indication for priority review in the United States and makes it potentially eligible to receive a transferable Priority Review Voucher, if approved. Assuming successful completion of the company’s development program, it plans to seek initial approval for TLC178 in RMS and focuses that a single-arm, response-oriented registration trial might be sufficient for approval. It also proposes clinical trials evaluating TLC178 in other STSs, for which TLC178 has already received from both the FDA and the European Medicines Agency an Orphan Drug Designation that could potentially provide marketing exclusivity for seven years in the United States (ten years in the European Union), and in non-small cell lung cancer. Approved Generic Products Ampholipad and Lipo-Dox are the company’s two generic products utilizing its NanoX technology, which have been approved for sale in Taiwan and Southeast Asia. It has entered into license agreements with third party distributors to sell its generic products in exchange for royalties. Ampholipad: Ampholipad, the company’s approved product in Taiwan and Macau, is liposomal amphotericin B for systemic fungal infection. Ampholipad is a generic of Gilead’s AmBisome and capable of delivering effective doses with a desirable toxicity profile. In June 2020, the Taiwan Food and Drug Administration approved the company’s Scale-up & Post-approval Changes application for Ampholipad, and scaled-up production is capable of exceeding a million vials a year. In August 2020, the Center for Drug Evaluation of the China National Medical Products Administration accepted the company’s Marketing Authorization Application for Ampholipad. Gilead’s AmBisome is not available in China. Discussions for commercialization of Ampholipad in Latin America, as well as North America and Europe are ongoing. Ampholipad is manufactured by Yung Shin Pharmaceuticals Ind. Co., Ltd., which is in compliance with GMP guidelines set forth by The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S). Lipo-Dox: Lipo-Dox is a NanoX doxorubicin product, which was approved by Taiwan’s Department of Health in 1998 for the treatment of breast cancer, ovarian cancer, and AIDS-related Kaposi’s sarcoma and multiple myeloma. Lipo-Dox, with its PEGylated liposomes design, reduces the rate at which the active substance is broken down, allowing it to circulate in the blood for a longer period of time. Lipo-Dox also reduces effects on non-cancer tissues and cells, hence has reduced cardiotoxicity compared to free form doxorubicin. Lipo-Dox has been licensed to TTY Biopharm Co., Ltd., a Taiwanese pharmaceutical company, which is in compliance with GMP guidelines set forth by PIC/S, for manufacturing and distribution in Taiwan and Southeast Asia. Strategy The company’s strategy is to develop and commercialize highly differentiated liposome-based products for indications associated with high unmet medical needs. The key elements of the company's strategy include to rapidly advance its sustained release pain management product candidates; selectively advance and/or partner out product candidate TLC399 for potentially longer management of retinal diseases; selectively advance and/or partner out its targeted delivery product candidates, which utilize NanoX, a technology proven in two approved products for sale in Asia; selectively pursue additional indications; continue to leverage its proprietary technology; take advantage of opportunities for streamlined regulatory approval; expand its pipeline; and continue to expand its global market. Manufacturing TLC599 and TLC399: The company’s TLC599 and TLC399 product candidates are manufactured by Yung Shin Pharmaceuticals, Ind. Co., Ltd (YSP), a Taiwan based, current good manufacturing practices -compliant manufacturer and global supplier for various injectable products. In May 2018, the company entered into a Clinical Manufacturing Agreement with Evonik Corporation (Evonik), which operates a GMP-compliant facility located in the United States, as its supplier of TLC599 drug product for its planned pivotal clinical trial. The company has planned for commercial supply of TLC599 to be manufactured by Evonik. Evonik has completed production of clinical batches, as well as submission batches of TLC599. TLC590: Clinical supply of TLC590 is manufactured by Shinlin Sinseng Pharmaceuticals, Ind. Co., Ltd, a Taiwan based, GMP-compliant manufacturer. The company has identified Baxter Oncology GmbH (Baxter) as its supplier of TLC590 for pivotal clinical trials. The company signed an agreement with Baxter in August 2018 to set up manufacturing equipment and is conducting technology transfer for clinical supply manufacture. TLC178: The company’s TLC178 product candidate is manufactured by Hospira Australia Pty Ltd. Intellectual Property As of December 31, 2020, the company had been granted 160 utility patents worldwide, including ten Taiwan patents, 14 United States patents, eight Japan patents, six New Zealand patents, eight China patents, five Australia patents, seven Korea patents, four Russian patents, six Hong Kong patents, four European patents, four South Africa patent four Canada patents and two Brazil patents. It also has 97 patent applications, which are under review in the above major markets (including the United States, Europe, China, Korea and Japan), as well as Taiwan, Australia, South Africa, India, Brazil, Mexico, Israel and Singapore jurisdictions, as well as 11 pending PCT patent application, relating to its product candidates. The patent terms for TLC599 and TLC399 extend into 2033 and the patent term for TLC178 extends into 2034. If issued, the patent term for TLC590 and additional patent families of TLC599 would extend into 2040 and 2039. The company owns all of the patents and patent applications relating to its four lead product candidates. TLC599: The company’s TLC599 intellectual property portfolio includes 12 issued patents and 13 patent applications. Its issued patents cover the methods of use of TLC599, were granted in the United States, Australia, New Zealand, Russia, Japan, China/Hong Kong, South Africa, South Korea and Taiwan, and are expected to expire in 2033. The company’s patent applications cover composition, as well as methods of use of TLC599 and are pending and under review in the United States, South Africa, Taiwan, Singapore, Russia, Korea, Japan, India, Hong Kong, Europe, Canada and Brazil, with expected expiry dates of 2039. TLC399: The company’s TLC399 intellectual property portfolio includes 95 issued patents and two patent applications. Its issued patents cover the composition of matter of TLC399, were granted in Taiwan, the United States, Canada, South Africa, Russia, New Zealand, Korea, Japan, Hong Kong, China, Australia and a series of European countries, and are expected to expire between 2029 and 2033. The company’s patent applications cover the composition of matter of TLC399. TLC590: The company’s TLC590 intellectual property portfolio includes 29 patent applications, which cover the composition of matter of TLC590, method of manufacturing and method of use of TLC590, and are pending, in the international phase of PCT applications and in Taiwan with expected expiry dates extending into 2040. TLC178: The company’s material TLC178 intellectual property portfolio includes 33 issued patents and five patent applications. Its issued patents cover the composition of matter of TLC178, were granted in Taiwan, China/Hong Kong, Japan, Korea, Australia, the United States and European countries and expected to expire in 2034. The company’s patent applications cover the composition of matter of TLC178 and are pending and under review in the United States, India, Hong Kong, China and Brazil, with expected expiry dates of 2034. The patent terms of the company’s BioSeizer platform for TLC599 and TLC399, as well as their use in treatment including, but not limited to US 9,789,062, US 10,322, 086, US 8,956,600, US 9,987,360, US 10,058,616 and US 10,350,294 and that of composition claim for TLC178, including but not limited to, US 9,700,511 approximately extend into 2033, 2029 and 2034, respectively. For TLC590, TLC399 and TLC599, the patent terms of novel composition claims and improved treatment method claims would extend into 2040, 2033 and 2039 respectively if issued. In addition to patents, the company has filed for trademark registration with the U.S. Patent and Trademark Office for ‘BioSeizer’, ‘NanoX’, ‘LipAD’, ‘Doxolipad’, ‘Delivering Hope for Life’, ‘tlc’ with designs and ‘tlc Taiwan Liposome Company’. Research and Development The company’s research and development expenses were NT$967.5 million (US$34.5 million) for the year ended December 31, 2020. Government Regulation Any products manufactured or distributed by the company pursuant to FDA approvals are subject to continuing regulation by the FDA, including manufacturing, periodic reporting, product sampling and distribution, advertising, promotion, drug shortage reporting, compliance with any post-approval requirements imposed as a conditional of approval, such as Phase 4 clinical trials, risk evaluation and mitigation strategy and surveillance, recordkeeping and reporting requirements, including adverse experiences. In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, affect the company’s business. History Taiwan Liposome Company, Ltd. was founded in 1997. The company was incorporated as a company limited by shares under the provisions of the Company Act of the Republic of China in 1997.