Asia Deal Watch: ReVance Licenses Chinese Rights To Botox Competitor To Fosun

With Phase III data in 2,800 patients for reducing frown lines, ReVance anticipates filing RT002 for US approval in 2019. ABL licenses two bispecific antibody candidates to TRIGR, while Sun looks to expand in dermatology with Pola buyout.

Scrip regularly covers business development and deal-making in the biopharmaceutical industry. Deal Watch is supported by deal intelligence from Strategic Transactions.

With BLA Expected In 2019, ReVance Gets $30m Up Front For Chinese Rights To RT002

California biotech ReVance Therapeutics Inc. unveiled two new developments Dec. 4 as it reported the completion of a 2,800-patient Phase III program for RT002, a long-acting aesthetic neuromodulator being studied in treating glabellar (frown) lines and obtained $30m up front from Shanghai Fosun Pharmaceutical Group Co. Ltd. for development and commercial rights to the candidate in mainland China, Hong Kong and Macau.

ReVance is developing daxibotulinimtoxin A for injection as a direct competitor to Allergan PLC’s Botox (onaboutlinimtoxin A) in cosmetic indications, with the possibility of less-frequent dosing. (Also see "Medical Aesthetics: A Untapped Pharma Market With Incoming Competition" - Scrip, 30 Nov, 2018.) Allergan, which markets Botox as both a cosmetic and therapeutic product, reported third quarter sales for the product on Oct. 30 of $216m in cosmetic indications and $407.4m in neuroscience and urology indications. (Also see "Allergan's Botox Holds Its Own In Migraine, Despite CGRP Competition" - Scrip, 30 Oct, 2018.) The product brought in nearly $880m in global revenues during the first nine months of 2018.

ReVance said the data will enable it to file RT002 for US approval in 2019 and also to begin investigating other indications for the injectable, such as crow’s feet and forehead lines. In the just-completed studies, the candidate showed 95% of patients responding to treatment by week four of therapy with efficacy for reducing the appearance of moderate-to-severe glabellar lines for 24 weeks, the company said.

Under its agreement with Fosun, in addition to the upfront cash ReVance can earn development and sales milestones of up $230.5m along with tiered royalties of future net sales of the product. The deal involves no transfer of intellectual property – ReVance will manufacture both clinical trial and commercial supply of RT002, with Fosun taking responsibility for clinical development, marketing and sales in its territories.

ABL Bio, TRIGR Ink $595m Bispecific Antibody Deal

ABL Bio Corp. announced an out-licensing agreement Nov. 30 with US-based TRIGR Therapeutics Inc. for ABL001, a bispecific antibody candidate targeting the angiogenic factors VEGF and DLL4, in a deal worth as much as $595m plus sales royalties.

Under the agreement, TRIGR is responsible for all subsequent global clinical development and commercialization activities for ABL001 in oncology, excluding South Korea, and in ophthalmology, excluding South Korea and Japan. ABL will receive an upfront payment of $5m. It is eligible to receive up to $595m in total with an upfront, clinical and commercial milestone payments and sales royalties for ABL001.

Dual blockade of both VEFG and DLL4 is emerging as the next frontier of angiogenic therapy as the combination of these two mechanisms has been shown to overcome VEGF inhibitor resistance. Three programs targeting anti-VEGF/DLL4 are undergoing clinical development: AbbVie Inc.’s ABT-165 which has recently entered Phase II in colorectal cancer and Oncomed Pharmaceuticals Inc.’s OMP305B83 in Phase Ib in platinum-resistant ovarian cancer, as well as ABL’s ABL001.

ABL001 (NOV1501) was selected as a co-development project for the immuno-oncology clinical trial from the National OncoVenture, a Korean government-funded oncology drug development program, and is being tested in a dose-escalation Phase Ia study at Samsung Medical Center in South Korea. ABL Bio and TRIGR Therapeutics plan to jointly proceed with a Phase Ib study.

In July, ABL announced a $554.3m deal with TRIGR for the global commercial rights to ABL’s pipeline of novel therapeutic antibodies to treat cancer. (Also see "Deal Watch: BioCryst Shareholder Dissent Scuttles Planned Merger With Idera" - Scrip, 13 Jul, 2018.) The company is slated to offer an initial public offering on South Korea’s Kosdaq market later this month.

Sun Acquires Japan’s Pola, Primes Derma Expansion

Sun Pharmaceutical Industries Ltd. said Nov. 26 that it has lined up a deal to acquire Pola Pharma Inc. to put in place an effective launchpad to expand into the dermatology segment in the Japanese market. Sun said that the equity consideration, on a debt-free and cash-free basis, for a 100% stake in Pola is approximately $1m.The deal is expected to close on or before Jan. 31, 2019, subject to completion of closing conditions.

Established in 2007, Tokyo-based Pola’s portfolio essentially comprises dermatology products and, in addition to R&D expertise, the firm brings with it two plants in Saitama, Japan, with capabilities to manufacture topical products and injectables. Pola Pharma is a 100% subsidiary of [Pola Orbis Holdings Inc.] of Japan.

Pola is expected to help Sun launch its specialty and generic dermatology products in the Japanese market in the future, strengthening its global presence in the area. Sun hopes to serve the Japanese pharmaceutical market more effectively through local manufacturing capabilities. Pola also offers dermo cosmetic products and ‘quasi-drugs ‘as part of its comprehensive skin-care solutions, according to its website, although it’s not immediately clear how Sun will pursue these areas.

Pola reported revenues of approximately $108m and a net loss of $7m on consolidated basis during 2017. Exports from Japan to other markets contribute less than 1% of Pola’s total revenues, Sun said in a filing to the Bombay Stock Exchange.

In 2016, Sun made its entry into Japan through the acquisition of a portfolio of 14 established prescription brands from Novartis AG for $293m. [See Deal] Later that year, Mitsubishi Tanabe Pharma Corp. was appointed as the distributor in Japan for the basket of brands acquired by Sun. (Also see "Sun Taps Mitsubishi For Ex-Novartis Japan Portfolio" - Scrip, 7 Sep, 2016.)

CBT, Bossan Tie Up To Develop Anticancer Combos

CBT Pharmaceuticals Inc. and Zhejiang Bossan Pharmaceutical Co. Ltd said on Nov. 26 they had entered into a clinical collaboration and license agreement to develop a combination of their respective pipeline anti-cancer assets. CBT will get exclusive, worldwide rights outside of Greater China to develop and commercialize ES-072, Bossan’s novel epidermal growth factor receptor (EGFR) inhibitor, in combination with CBT’s proprietary c-Met inhibitor CBT-101 and anti-PD1 antibody CBT-501.

The companies will conduct joint clinical trials of CBT-101, and/or CBT-501 in combination with ES-072, with CBT to be responsible for conducting clinical trials globally outside of Greater China. A joint steering committee and joint clinical development subcommittee will be formed to oversee and coordinate research, development, manufacturing, regulatory and commercial activities.

ES-072 is a covalent, irreversible, mutant-selective EGFR inhibitor that has nanomolar inhibitory potency against EGFR and its T790M mutation. Preclinical data suggest it is able to cross the blood-brain barrier. The drug is currently in a Phase I trial in China through Bossan for non-small cell lung cancer patients with mutant EGFR. The Hangzhou-based company focuses on the development of targeted, small molecule therapeutics against tumors.

CBT-101, a small molecule drug, targets the epithelial-to-mesenchymal transition pathway that is dysregulated in several tumors, and is a specific inhibitor of the c-Met receptor. It has demonstrated a tumor inhibitory effect in a variety of human primary c-Met amplified gastric, hepatic, pancreatic and lung cancer xenograft animal models with c-Met fusions, mutations or amplifications. Development is already under way in China, where it is known as PLB1001 and is licensed to Beijing Pearl Biotechnology Co. Ltd.

CBT-501 (genolizumab), an IgG4 humanized monoclonal antibody against the PD-1 membrane receptor, has a comparable efficacy profile to the marketed anti-PD-1 antibodies nivolumab (Bristol-Myers Squibb Co.’s Opdivo) and pembrolizumab (Merck & Co. Inc.’s Keytruda), and a favorable profile with very low antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity activity, CBT notes. In China, CBT-501 is referred to as GB226, where it is being developed by partner Genor Biopharma Co. Ltd.

CBT, led by global CEO and OrbiMed Venture Partner Guo-Liang Yu, recently began the APOLLO clinical trial program, in which it is assessing CBT-101 in combination with CBT-501 for hepatocellular carcinoma, and CBT-101 plus nivolumab for renal cell carcinoma.

FUJIFILM Licenses Oncology Radiopharmaceutical To Novartis Affiliate

Fujifilm Toyama Chemical Co. Ltd. out-licensed global rights, except for Japan, Dec. 3 for its radiopharmaceutical candidate FF-10158 in oncology indications to Advanced Accelerator Applications SA, a French affiliate of Novartis. AAA gets an exclusive option and license to develop and commercialize the candidate in exchange for an undisclosed upfront payment and future milestones and royalties.

FF-10158 is a preclinical small-molecule antagonist with affinity for the integrin alphavbeta3 and alphavbeta5 receptors. Increased expression of the former is associated with invasive growth and poor survival in glioblastoma patients, AAA says, so that will be among the initial indications it plans for a program to develop theragnostic compounds based on FF-10158.

Telix, Nihon Partner On Theragnostics For Renal Cell Cancer

In another deal focused on development of theragnostics – which combine therapeutic and diagnostic functions – Australia’s  Telix Pharmaceuticals Ltd. and Japan’s Nihon Medi-Physics Co. Ltd. announced Nov. 29 that they will partner on an effort to evaluate the feasibility of 225Ac-labeled (actinium) antibodies for the treatment of clear-cell renal cell cancer (ccRCC). No financial terms were disclosed.

As an alpha-emitting nuclide, 225Ac is thought to offer significant potential to treat cancer via nuclear medicine techniques, the companies say. They will collaborate to combine Nihon’s novel linker chemistry with Telix’s CAIX-targeted antibodies and then conduct proof-of-concept studies jointly.

Hansoh Licenses US Rights To Injectable Cancer Drugs To Hikma

China’s Hansoh Pharmaceutical Group signed a five-year licensing and supply agreement Nov. 27 with UK-based Hikma Pharmaceuticals PLC for a suite of injectable cancer therapies that the latter company hopes to introduce to the US market. No financial terms were disclosed.

Hikma gets the rights for the next five years for a group of products Hansoh expects to file for US FDA approval within the next 12 months. In a statement, Hikma noted that currently one of six generic injectable therapeutics used in the US hospital setting is a Hikma product.

You can read more about other licensing deals that have been covered in depth by Scrip in recent days below:

(Also see "UPDATED: Clear 'Yes' From Shareholders On Takeda/Shire Deal " - Scrip, 4 Dec, 2018.)

Dec. 5, 2018, was a big day in the timeline of Takeda Pharmaceutical Co. Ltd.'s proposed acquisition of Shire PLC, with shareholder votes being held at both companies. The deal passed the first of its final hurdles, easily receiving approval at an EGM of Takeda shareholders.