Deal Watch: AstraZeneca Offloads US Anesthesiology Portfolio To Aspen

Merck adds to its immuno-oncology R&D heft with purchase of Rigontec, while Allergan will collaborate with Lyndra to produce once-weekly drugs for Alzheimer’s disease.

Scrip regularly covers business development and deal-making in the biopharmaceutical industry. Below is a roundup of some of the most noteworthy recent transactions. Deal Watch is supported by deal intelligence from Strategic Transactions.

AstraZeneca Divests US Rights To Anesthetics Portfolio To Aspen

AstraZeneca PLC is selling the US rights to a portfolio of anesthetics to Aspen Pharmacare Holdings Ltd. in a deal worth up to $766m, having already sold global rights excluding the US to the South African-based group last year.

The seven medicines are Diprivan (propofol), EMLA (lidocaine/prilocaine), Xylocaine/Xylocard/Xyloproct (lidocaine/lignocaine), Marcaine (bupivacaine), Naropin (ropivacaine), Carbocaine (mepivacaine) and Citanest (prilocaine). AstraZeneca will continue to manufacture and supply the medicines to Aspen during a transition period of up to five years.

Under the terms of the agreement announced Sept. 14, Aspen will acquire the remaining rights to the intellectual property and manufacturing know-how related to the portfolio for an upfront payment of $555m. It will pay up to $211m more in performance-related milestones from now up to Nov. 30, 2019.

The companies teamed up initially in June 2016 when Aspen acquired the non-US rights to the portfolio for an upfront consideration of $520m. That deal includes up to $250m in a product sales-related payment, as well as double-digit royalties. (Also see "Aspen Acquires AstraZeneca Anesthetics Portfolio Ex-US" - Scrip, 9 Jun, 2016.)

The sale is a continuation of AstraZeneca's strategy to divest non-core assets and focus on its three main therapy areas of oncology, cardiovascular and metabolic diseases and respiratory.

Merck Buys Rigontec For More Than $550m

Merck & Co. Inc. will pay €115m ($136.9m) up front to acquire Rigontec GMBH, a privately held biotech developing immuno-oncology therapies targeting the retinoic acid-inducible gene I (RIG-I) pathway in the innate immune system. The Sept. 6 deal also includes up to €349m in development, regulatory, and commercialization earn-outs. [See Deal] Total deal value of €464m equates to approximately $553m.

Three-year old Rigontec was spun out of the University of Bonn and is developing its lead candidate RGT100 in Phase I trials for solid tumors and lymphoma. The compound targets the RIG-I receptor to activate the body’s innate immune response and produce interferons or silence certain genes, both resulting in tumor cell death. The company notes that in addition to cancer, the technology can be applied to infectious and inflammatory disease therapies as well.

The acquisition enhances Merck’s immuno-oncology pipeline and gives the company additional assets that potentially be used in combination with other of the pharma’s projects. Rigontec raised about €30m through its Series A round shortly after foundation from a syndicate of investors that includes Boehringer Ingelheim Venture Fund, Forbion Capital Partners, High-Tech Grunderfonds, MP Healthcare Venture Management, NRW.BANK, Sunstone Capital and Wellington Partners Life Sciences. [See Deal]

Basilea Gets EU, Israeli Rights to Cardiome's Ceftobiprole

Basilea Pharmaceutica International Ltd. licensed Cardiome Pharma Corp. exclusive rights Sept. 12 to distribute its antibiotic Zevtera (ceftobiprole) in more than 30 European countries (excluding Nordic countries) and Israel. [See Deal] Cardiome will pay CHF5m ($5.3m) plus pre-specified regulatory and commercial milestones. Basilea will supply Cardiome with ceftobiprole at a transfer price and Cardiome is in charge of regulatory and commercial activities in the licensed territories.

The antibiotic has been approved in 13 countries in Europe, and is also sold under the Mabelio brand name. The IV cephalosporin antibiotic is used for treating gram-positive and gram-negative bacteria including methicillin-susceptible and resistant Staphylococcus aureus and Pseudomonas, as well as community- and hospital-acquired pneumonia.

Under previous tie-ups, Grupo Biotoscana SL has rights in Latin America [See Deal], Unimedic Pharma AB in Sweden, Denmark, Norway and Finland [See Deal], and Hikma Pharmaceuticals PLC in the Middle East and North Africa region. [See Deal]

Allergan, Lyndra Collaborate On Once-Weekly Alzheimer’s Therapeutics

Allergan PLC and Lyndra Inc. agreed on Sept. 7 to collaborate on the development of oral, once-weekly formulations of Allergan's existing Alzheimer's disease (AD) therapeutics. [See Deal] In addition to an AD candidate, Allergan may select another compound within any therapeutic area to develop as part of the deal. In exchange, Lyndra will receive $15m up front and $90m in development and regulatory milestones for the two programs.

The partnership will leverage Lyndra's ultra-long-acting sustained-release oral dosage delivery platform (invented at and licensed from Massachusetts Institute of Technology), which converts both large- and small-molecule daily-dosed medications into a weekly or monthly schedule, enabling linear drug release and sustaining therapeutic serum levels for seven days or more. Lyndra says its technology is designed to optimize the pharmacokinetic profile of the dosage form and promote better patient compliance versus daily medication regimens.

Although specific compounds were not yet disclosed, Allergan already markets the oral daily AD drugs Namenda/Namenda XR (memantine HCl) and Namzaric (donepezil/memantine ER) and also has multiple AD candidates in its pipeline, including the Phase II CPC201 (donepezil/solifenacin; acquired in its 2016 acquisition of Chase Pharmaceuticals Corp.) [See Deal], as well as preclinical and Phase I selective muscarinic receptor agonists licensed from Heptares Therapeutics Ltd. last year. [See Deal]

Vectura Obtains US Rights To Mid-Stage Pulmatrix COPD Candidate

Pulmatrix Inc. licensed Vectura Group PLC rights Sept. 6 to develop, manufacture, and commercialize its Phase II chronic obstructive pulmonary disease candidate PUR0200 in the US. [See Deal] Vectura and/or its partners will pay for all development costs. Pulmatrix will provide the PUR0200 data package and help transfer of development and manufacturing activities to Vectura.

Pulmatrix will receive a $1m technology access fee upon the achievement of agreed-upon development criteria. Vectura will pay the company a mid-teen percentage of future revenues (Strategic Transactions assumes 14%-16%) based on the development and commercialization of PUR0200 and any products that contain PUR0200.

Once-daily PUR0200 incorporates the long-acting muscarinic antagonist tiotropium bromide and is delivered via Pulmatrix's iSPERSE (inhaled Small Particles Easily ReSpirable and Emitted) dry powder technology. Under a June 2015 tie-up, Mylan NV holds ex-US development rights to the COPD compound. [See Deal]

HitGen Signs Collaborative Research Partnerships With Takeda, Cocrystal

Chinese biotech HitGen Ltd. agreed to two collaborative research deals in September with Takeda Pharmaceutical Co. Ltd. and Cocrystal Pharma Inc. on discovering novel small molecule drug candidates based on HitGen’s DNA-encoded library (DEL) technology platform.

HitGen will help its partners to discover lead compounds based on its research capabilities in the design, synthesis and screening of multiple proprietary DELs, which enable a large number of leads to be rapidly identified for specific drug targets.

Under an agreement announced Sept. 11, the novel leads discovered under the partnership with Takeda for multiple targets will be licensed exclusively to the Japanese pharma, in exchange for upfront compensation and milestone payments to HitGen.

In the Sept. 5 deal with Cocrystal, the US biotech will use its industrialized crystallization and co-crystallization technology to determine at near-atomic resolution the structures of HitGen's selected library compounds that interact with drug targets. And then, a private computer software company, InterX, will use its advanced proprietary software to design superior drugs from the information provided by Cocrystal and HitGen.

HitGen has entered into similar research collaborations with Merck and Pfizer Inc. this year using HitGen's DELs to potentially bring efficiencies, optimization and time savings in drug development.

HitGen’s DELs contain more than 90bn novel, diverse, drug-like small molecule and macrocycle compounds. These compounds are synthesized from many hundreds of distinct chemical scaffolds, designed with tractable chemistry and proven results for finding drug leads against targets from known and novel protein classes.

Wuxi Fortune And Andarix Team For Chinese Commercialization Of Tozaride

Wuxi Fortune Pharmaceutical Co. Ltd. and US-based Andarix Pharmaceuticals inked an agreement Sept. 6 to develop and commercialize Tozaride for lung and other cancers treatment in the Chinese market.

Tozaride, also known as Rhenium (Re) 188-P2045, is a targeted therapy that combines a high-affinity somatostatin receptor-binding peptide with the high-energy, beta-emitting radionuclide Rhenium-188, which can rapidly internalize with somatostatin receptors that are over expressed in both small cell and non-small cell lung cancers, as well as in neuroendocrine cancers, to become a highly specific targeting agent. Re188-P2045 has received Orphan Drug designation for both small cell lung and pancreatic cancers, and is preparing to enter Phase II clinical studies in the US.

Under the agreement, Wuxi Fortune will work with Andarix on the clinical development of Tozaride in China, and will own certain specific marketing rights to the drug in China. This past August, Wuxi Fortune said it planned to acquire a 20% stake of Andarix by investing $2m in the company. The proceeds will be used to advance Phase II trials of its lead drug candidate in lung cancer, and increase the company’s liquidity.

RMX Biopharma Links With Daehwa For Oral Paclitaxel

Daehwa Pharmaceutical Co. Ltd. said Sept. 6 that it has signed a $25m licensing out agreement with China's RMX Biopharma for the South Korean company's oral paclitaxel Liporaxel. Previously known as DHP107, the drug is the world's first approved oral paclitaxel. It was approved in South Korea in September 2016 for progressive and metastatic gastric cancer.

Under the agreement, RMX Biopharma gets the drug's exclusive rights in China, Taiwan, Hong Kong and Thailand, while Daehwa will keep its rights for the rest of the world. The South Korean company will receive KRW4bn in upfront payment and KRW24.3bn in milestones plus unspecified amount of sales royalties if the drug is commercialized.

HanAll Grants Harbour BioMed Chinese Rights To Autoimmune, Dry Eye Drugs

South Korea's HanAll BioPharma Co. Ltd. said Sept. 12 that it has licensed out its novel autoimmune disease drug and ophthalmic solution for dry eye disease to China's Harbour BioMed in a deal worth $81m. Harbour Biomed gets exclusive rights to the drugs in China, Hong Kong, Taiwan and Macau. HanAll will receive $4m in up front payment and up to $77m in milestones plus separate sales royalties, the South Korean company said in a disclosure to the stock market.

HL161, its novel anti-FcRn (neonatal Fc receptor) antibody for autoimmune diseases, has completed a preclinical study. The company is preparing for a Phase I study of the first-in-class drug in Australia.

HL036, its anti-TNF bio ophthalmic solution for dry eye disease, has completed a Phase I study in South Korea. The company has filed for an IND to the US FDA and is set to begin a Phase II US study of the biobetter this year. HL036 is a joint development program with Daewoong Pharmaceutical Co. Ltd., which acquired HanAll Biopharma in 2015. [See Deal]

Abivax, Evotec Ally In Infectious Diseases

Evotec AG and Abivaxare teaming up to discover and develop small molecule therapies for various serious viral infectious diseases. [See Deal] Abivax's antiviral platform is based on a chemical library of more than 1,000 small molecules that block viral replication by inhibiting mRNA biogenesis. It targets the formation of RNA-protein complexes in the nucleus or the cytoplasm of the infected cell during viral infection.

Under the agreement announced Sept. 7, Abivax will use the technology to identify hits and will conduct in vitro and in vivo pharmacology studies. Evotec will use its discovery platform to optimize the candidates and perform early development including pharmacology, ADME, computational chemistry and mechanism of action studies.

The parties will initially focus on targets for RSV, influenza and dengue, which have already been identified by Abivax. Abivax gets commercial rights to any resulting drugs. The company has used its IP to successfully create its Phase II HIV compound ABX464.

MEI Gets Global Voruciclib Rights From Presage

Presage Biosciences Inc. granted MEI Pharma Inc. exclusive global rights Sept. 5 to develop, manufacture and sell the oral CDK-4 inhibitor voruciclib, which has been tested in Phase I cancer trials. [See Deal] Presage gets $2.9m up front; up to $181m in development, regulatory and sales milestones (including $2m upon dosing of the first patient in the first registration trial and up to $2.9m in additional pre-approval milestones); and mid-single-digit royalties. (Strategic Transactions estimates 4%-6%.)

Presage licensed voruciclib from Piramal Enterprises Ltd. in 2015 after Piramal had discontinued development. [See Deal] MEI will work on the candidate both as a monotherapy and in combination with other anticancer therapies including venetoclax (AbbVie Inc./Genentech Inc.’s Venclexta), which has shown synergistic activity when combined with voruciclib for chronic lymphocytic leukemia.

MEI's pipeline already includes lead project pracinostat, an HDAC inhibitor in late-stage trials for AML, myelodysplastic syndrome and myelofibrosis; ME401, in Phase I for CLL and follicular lymphoma; and ME344, in Phase II for HER2-negative breast cancer.

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

(Also see "Clinigen Takes Aim At Unlicensed-To-Licensed Strategy With Quantum Buy" - Scrip, 13 Sep, 2017.)	Extending its business in continental Europe, in niche generics and in the further development of unlicensed medicines are some of the drivers of Clinigen Group PLC's latest proposed acquisition.
(Also see "Achillion Keeps Focus On Complement Factor D Inhibitors As J&J Exits HCV" - Scrip, 11 Sep, 2017.)	Johnson & Johnson's decision to stop HCV development and end its partnership with Achillion Pharmaceuticals Inc. has a ripple effect for the smaller biotech's strategy.
(Also see "Boehringer Taps Gubra For Early-Stage Obesity Deal" - Scrip, 11 Sep, 2017.)	Boehringer Ingelheim GMBH has signed a collaboration with Denmark-based Gubra ApS focusing on the development of peptides to treat obesity, with Gubra to receive up to €250m in upfront and potential milestone payments.
(Also see "Allergan Shifts Restasis Patents To Native American Tribe To Invoke Immunity From IPR" - Scrip, 9 Sep, 2017.)	The tribe will move to get IPR proceedings dismissed, but the strategy isn't expected to affect ANDA litigation. Allergan's CEO said the company could use a similar approach with other patents and notes that other companies may follow.
(Also see "Bicycle Partners With Biogen Spinout Against Rare Blood Disorders" - Scrip, 6 Sep, 2017.)	Bicycle Therapeutics Ltd. and Biogen Inc. spinoff Bioverativ Inc. have teamed up to develop novel treatments for hemophilia and sickle cell disease under a multi-million-dollar discovery and development agreement.