Deal Watch: Allergan Keeps After Hair Loss With Exicure Deal

Allergan has tried to go after alopecia in the past; Exicure brings a new spherical nucleic acid (SNA) technology. In other recent deals, AstraZeneca sells Seroquel, Losec rights to Germany’s Cheplapharm.

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

Allergan Extends Its Aesthetics Footprint With Exicure Hair Loss Deal

Allergan PLC has developed a deep presence in the medical aesthetics field with its Botox, Juvederm and CoolSculpting businesses, among others, which is a key part of what attracted AbbVie Inc. to bid for the company in June. Ahead of the closing of that merger early next year, Allergan is adding hair loss conditions to its aesthetics specialization with a new partnership with Exicure Inc. The collaboration, announced 14 November, is to discover and develop novel treatments for hair loss disorders, based on Exicure’s proprietary spherical nucleic acid (SNA) technology.

Under the agreement, Exicure received a $25m upfront payment and will conduct discovery and development in two collaboration programs for hair loss disorders. Allergan holds option rights and will be responsible for clinical development and commercialization for any licensed products; Exicure will be eligible for development and regulatory milestones up to $97.5m per program and commercial milestones up to $265m per program, as well as tiered royalties of mid-single digit to mid-teens percentages of worldwide net product sales.

The only condition named in the release is androgenetic alopecia, also known as pattern baldness, which according to Exicure affects approximately 50 million men and 30 million women in the US, and an estimated $3.5bn-plus is spent on largely ineffective treatments annually. Allergan has previous experience in androgenetic alopecia with setipiprant, gained from its acquisition of Kythera Biopharmaceuticals Inc. in 2015, but the company appears to have dropped the candidate after a disappointing Phase II trial. Allergan also attempted to develop Latisse, its eyelash growth drug, for alopecia, part of its long-standing interest in the hair loss space.

There has been notable drug development around alopecia areata, an autoimmune disorder that causes sudden hair loss. That’s been lead by Pfizer Inc.’s PF-06651600, a JAK3/TEC family kinase inhibitor in Phase III, which holds a breakthrough designation from the US Food & Drug Administration. Concert Pharmaceuticals Inc. is also working on a JAK inhibitor project with its CTP-543, a deuterated version of ruxolitinib (Novartis AG/Incyte Corp.’s Jakafi), while Cassiopea is moving into Phase III with its topical anti-androgen Breezula (clascoterone).  (Also see "Cassiopea Hails Breezula's 'Good Hair Day' And Plans FDA Talks On Phase III " - Scrip, 16 Apr, 2019.)

Allergan has a long-standing interest in hair loss, but the Exicure deal joins another recent investment in the space. In June, Stemson Therapeutics announced Allergan had made a significant investment in its seed financing round, which would help Stemson advance its induced pluripotenti stem cell (iPSC) product development for clinical trials “and provide Allergan with a promising new product pipeline” for its aesthetics portfolio. The start-up believes as iPSCs can develop into any cell type in the body, its cell therapies will be able to generate new hair follicles.

Bayer Bets On Biomolecular Condensates With Dewpoint

Bayer AG is looking to a partnership with Dewpoint Therapeutics to combine the biotech’s biomolecular condensate platform with its small molecule library to better target the proteome. The research and development agreement, announced 14 November, is worth up to $100m and includes option rights; the research will focus on cardiovascular and gynecological diseases.

Biomolecular condensates are droplet-like membraneless organelles that carry out a variety of functions in cells, but have been understudied because they are difficult to analyze with traditional drug discovery methods, the partners explained. Bayer believes “new analytic tools and a growing understanding of biomolecular condensates could provide new insights into cellular functions that previously have not been considered by scientists in drug development, enabling us to identify novel pharmacological targets for future therapies.”

The collaboration will develop local capabilities at Dewpoint’s Dresden, Germany, facility, and follows Bayer’s participation in Dewpoint’s January 2019 series A round through the Leaps by Bayer unit. (Also see "Finance Watch: Bitcoin For Biopharma? Agenus Gives BEST A Shot" - Scrip, 30 Jan, 2019.)

Sarepta And StrideBio Take Steps Toward Novel Gene Therapies

Rare disease specialist Sarepta Therapeutics Inc. is working with StrideBio Inc. to develop in vivo adeno-associated viral-based therapies for up to eight central nervous system (CNS) and neuromuscular targets, in a collaboration announced 14 November. StrideBio brings a novel, structure-driven capsid technology to enhance specific tropism to tissues of interest and evade neutralizing antibodies.

Sarepta gains an exclusive license on the first four CNS targets, which are MECP2 (Rett syndrome), SCN1A (Dravet syndrome), UBE3A (Angelman syndrome), and NPC1 (Niemann-Pick). StrideBio will conduction the IND-enabling R&D and manufacturing. Sarepta will also have an exclusive option to four additional CNS/neuromuscular targets based on StrideBio’s capsid technology. 

Menlo And Foamix Merge Into Dermatology Play

Foamix Pharmaceuticals Ltd. and Menlo Therapeutics Inc. announced their definitive merger agreement 11 November to create a dermatology-focused company. The combined company will build off of Foamix’s recently approved acne therapeutic Amzeeq (minocycline topical foam), which is slated to launch in January 2020. Foamix also has an NDA pending for FMX103, a minocycline foam for treatment of moderate-to-severe papulopustular rosacea, and a combination of minocycline and adapalene, FCD105, for acne. Menlo brings the late-stage candidate is serlopitant, in Phase III for its lead indication, pruritis associated with prurigo nodularis (PN), which has breakthrough status with the FDA.

The merger is a stock-for-stock exchange with a premium to Menlo if both Phase III PN trials are successful; it also includes a mechanism to provide more shares to Foamix shareholders to provide a downside adjustment if one or both PN trials do not hit their primary endpoint. Foamix shareholders are expected to own approximately 59% and Menlo shareholders approximately 41% of the combined company, subject to adjustment.

Lilly, Boehringer Rework Diabetes Alliance To Center On Jardiance

Boehringer Ingelheim International GmbH and Eli Lilly & Co. are restructuring their eight-year diabetes alliance so that it will now target joint efforts solely on Jardiance (empagliflozin), their partnered, best-selling selective sodium glucose cotransporter-2 (SGLT-2) inhibitor.

The duo on 4 November said that, as of 1 January 2020, their alliance will focus its combined expertise and investment on the continued development and commercialization of Jardiance in type 2 diabetes, heart failure and chronic kidney disease.

BI’s Trajenta/Tradjenta (linagliptin) and Lilly’s Basaglar (insulin glargine) will continue to be part of their alliance. But the companies said primary responsibility for development and commercialization of each of those two diabetes drugs will henceforth be led by the respective “innovator” company. BI will thus continue as strategic lead for Trajenta, and Lilly for Basaglar.

The companies’ diabetes alliance was originally one of the largest risk-sharing collaborations to be entered into when signed in 2011, with Lilly gaining access to two oral drugs, the DPP4 inhibitor linagliptin and the SGLT-2 inhibitor empagliflozin, while BI entered a new therapeutic area with the help of Lilly, which has a long history in marketing diabetes therapies. (Also see "Lilly/BI Eye Diabetes Leadership In Expansive Risk-Sharing Collaboration" - Pink Sheet, 11 Jan, 2011.)

Under the newly amended and restated agreement, there will be a revised margin-sharing structure for ongoing payments starting from New Year’s Day 2020.

Lilly said the pact’s revamp would not alter its 2019 financial guidance or 2020 financial goals, and that the specific impact on the upcoming year will be incorporated into Lilly's 2020 guidance, currently scheduled to be issued on 17 December. No further details were provided.

AstraZeneca Sells Mature Brands For $421m+

AstraZeneca PLC sold rights to its omeprazole and quetiapine brand portfolios in certain markets on 30 October to Germany’s Cheplapharm Arzneimittel GmbH. The move is part of the UK group’s ongoing policy of offloading mature brands to enable reinvestment in its core therapy areas of oncology, respiratory and cardiovascular, renal and metabolic disease.

Cheplapharm will pay $178m up front for rights to Seroquel and Seroquel XR (quetiapine fumarate immediate and extended release), which are used to treat schizophrenia and bipolar disorder, in Europe and Russia, where the products are off-patent. Cheplapharm has also agreed to make sales-contingent payments of up to $61m. The deal is expected to close before the end of the 2019.

Sales of the Seroquel products in Russia and Europe totaled $108m in 2018.

AstraZeneca sold rights to the Seroquel brands in UK, China and other international markets to Luye Pharma Group Ltd. in 2018, for $538m. [See Deal] In 2017, the products posted sales of $148m in the markets covered by the deal.

Cheplapharm is also acquiring global rights to the proton pump inhibitor Losec (omeprazole), excluding China, Japan, the US and Mexico. It is paying $243m plus sales-contingent milestones of up to $33m in 2021 and 2022. Product sales in the regions covered by the deal totaled $98m in 2018, mostly in emerging markets.

Losec, which is also marketed under brands including Acimax, Antra, Mepral, Mopral, Omepral and Zoltum, is used to treat gastro-esophageal reflux disease. AstraZeneca had previously sold rights to the product in the US, Japan and Mexico, as well as rights to the over-the-counter version in France, Finland, Ireland, New Zealand and the Netherlands.

Allogene Buys Into Notch, Partners On Allogeneic Stem Cell Therapies

Allogene Therapeutics Inc. acquired a 25% stake in Toronto start-up Notch Therapeutics Inc. and signed a licensing agreement and partnership with that company on 5 November to develop allogeneic stem cell therapy candidates for hematologic cancer indications. Allogene takes a seat on Notch’s board under the agreement, which specifies that Notch will perform preclinical research to optimize potential induced pluripotent stem cell candidates for the South San Francisco-based firm.

Notch, founded in 2018, gets $10m up front, can earn $7.25m in research milestones, up to $4m per target specified in the agreement for certain preclinical development milestones, and up to $283m per target and cell type for clinical, regulatory and commercial milestones under the agreement. In addition, the Canadian biotech could earn tiered royalties on net sales of any product reaching market out of the collaboration.

Notch will employ its Engineered Thymic Niche (ENT) platform technology to create iPSC candidates from T cells or natural killer cells for therapeutic application in non-Hodgkin lymphoma, leukemia and multiple myeloma. Allogene will perform clinical development of resulting AlloCAR T cell therapy candidates and hold worldwide commercial rights.

Novo Nordisk Obtains Preclinical NASH Drug From UBE

Novo Nordisk AS, which recently has been expanding on its diabetes-centric business model to focus on non-alcoholic steatohepatitis (NASH) R&D, licensed exclusive worldwide rights on 7 November to preclinical UD-014 from Japan’s UBE Industries Ltd. Specific financial terms were not revealed, but UBE gets an upfront cash payment and can earn development and sales milestones plus tiered net sales royalties under the agreement.

Based on the anti-inflammatory properties and anti-oxidative effect the compound has shown in preclinical studies, Novo believes the selective semicarbizide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) inhibitor could offer a treatment option for NASH patients. Under the deal, the Danish pharma assumes all development, manufacturing and commercialization of the agent.

In April, Novo signed an alliance with Gilead Sciences Inc. to test its GLP1 analog Ozempic with a pair of Phase II candidates at Gilead in NASH combination therapy. [See Deal]

Merck Teams With Promega On Keytruda Companion Diagnostic

Merck & Co. Inc. inked a global collaboration on 6 November with Promega Corp. to develop an on-label, solid tumor companion diagnostic for Keytruda (pembrolizumab) for microsatellite instability status (MSI). No financial terms were disclosed but the two companies plan to seek approval first of the diagnostic in the US and China. The Wisconsin biotech says it developed the technology for the Promega MSI CDx more than a decade ago and asserts that it can characterize tumors to guide therapeutic choices in MSI-high cancer types.

Amneal Obtains US Right’s To Kashiv Myasthenia Gravis Candidate

Two neighboring US biotechs agreed to a licensing deal on 6 November around an early-stage myasthenia gravis candidate, as Amneal Pharmaceuticals LLC acquired US commercial rights from Kashiv BioSciences LLC for K127 (pyridostigmine), which has demonstrated proof-of-concept in a Phase I pharmacokinetic study. Both companies are headquartered in Bridgewater, NJ.

Kashiv gets $1.5m up front for the rights to the once-daily, extended-release formulation of pyridostigmine, an off-patent acetylcholinesterase inhibitor. It also can earn up to $16.5m in development and regulatory milestones, as well as tiered net sales royalties.

Kashiv, which will be responsible for ongoing development and clinical work, said K127 could provide rapid onset of therapy and 24-hour duration to improve symptom control, tolerability and quality of life for myasthenia gravis patients, while encouraging better therapeutic compliance. In addition to commercial rights, Amneal also will be responsible for filing the new drug application (NDA) with the US Food and Drug Administration. (Also see "Amneal Will Go After 505(b)(2) Opportunity Under Patels’ Leadership" - Generics Bulletin, 7 Aug, 2019.)

Regeneron To Evaluate Vyriad’s Oncolytic Viruses

A Phase II study of a combination of Regeneron Pharmaceuticals Inc.’s PD-1 inhibitor, Libtayo (cemiplimab-rwlc), and Vyriad Inc.’s oncolytic vesicular stomatitis virus (VSV)-based agent, Voyager-V1, is expected to start in 2020 in multiple cancer types, as part of a strategic agreement between the two companies announced on 6 November.

In a five-year collaborative effort, Vyriad will work exclusively with Regeneron to develop new vesicular stomatitis virus-based oncolytic virus treatments, and the Rochester, MN-based biotech will receive an equity investment from Regeneron, as well as milestones and royalties, on any net sales of VSV-based collaboration products. In return, Regeneron will get an exclusive option to license Voyager-V1 and other products arising from the collaboration.

The Voyager V1 virus has been engineered to contain interferon-beta and reporter genes, and is programmed to attack cancer cells rather than healthy cells, activate the immune system, and help turn “cold” tumors “hot” and thereby recognizable by immune cells, enhancing the effects of PD-1 inhibitors. VSV is a common infection of farm animals including cattle and horses, but is little seen in humans, who do not have prior immunity.

Seattle Genetics Licenses BeiGene Asian Rights To Preclinical Candidate

Seattle Genetics Inc. and BeiGene Ltd. announced a license pact on 5 November for an advanced preclinical product candidate for treating cancer. The agent utilizes a proprietary Seattle Genetics antibody-based technology and is expected to advance into clinical trials in the first half of 2020.

The agreement entails Seattle Genetics retaining rights to the product candidate in the US, Canada and Latin American countries, as well as for Europe and Japan. BeiGene obtains rights to develop and commercialize the product candidate in Asia, except in Japan, and the rest of the world.

Seattle Genetics will lead global development of the asset while BeiGene will fund and operationalize the portion of global clinical trials attributable to its territories. BeiGene will also be responsible for all clinical development and regulatory submissions specific to its territories. Seattle Genetics will receive an upfront payment and is eligible to receive progress-dependent milestones for a total deal value of up to $160m and tiered royalties on any product sales.

Stay tuned for the next issue of Deal Watch. You can read more about other deals that have been covered in depth by Scrip and Generics Bulletin in recent days below:

(Also see "Merck Acquires Novel Neurodegenerative Disease Target With Calporta Buy" - Scrip, 13 Nov, 2019.)	The deal worth up to $576m gives Merck what Calporta Therapeutics Inc. founding investor Avalon believes is the most advanced program targeting TRPML1, a lysosomal ion channel implicated in neurodegenerative diseases when the lysosome stops clearing debris from cells.
(Also see "Lupin Offloads Kyowa Pharma For $525m But Not Exiting Japan " - Scrip, 11 Nov, 2019.)	Lupin Pharmaceuticals Inc. plans to invest in acquisitions and organic growth in the US and India after selling Japanese subsidiary Kyowa Pharmaceutical Industry Co. Ltd. for an enterprise value of around $525m to Japan private equity group Unison Capital. But the Indian firm stresses it is not exiting Japan and will continue to look for marketing partnerships.
(Also see "Samsung Bioepis Adds To Biogen Collaboration" - Generics Bulletin, 7 Nov, 2019.)	Samsung Bioepis Co. Ltd. and Biogen Inc. have agreed a marketing deal for “next generation” biosimilars aflibercept and ranibizumab in the US, Canada, Europe, Japan and Australia, as well as providing an option for Biogen to extend its existing deal to market anti-TNF biosimilars adalimumab, etanercept and infliximab in Europe and adding a further option for rights to sell these three biosimilars in China.
(Also see "Evotec, Vifor JV To Fight Kidney Disease " - Scrip, 6 Nov, 2019.)	Evotec SE’s CSO says its new joint venture with Vifor Pharma Group will use patient-driven data to identify and develop targeted therapies to treat kidney disease with.
(Also see "Alvotech And Stada Make Biosimilars Pact" - Generics Bulletin, 7 Nov, 2019.)	Alvotech and Stada Arzneimittel AG have struck a deal that will give Stada exclusive rights to sell seven Alvotech biosimilars “in all key European markets” as well as certain other territories.
( (Also see "Sun Allies With AZ To Drive China Oncology Push" - Scrip, 6 Nov, 2019.))	India's Sun Pharmaceutical Industries Ltd. joins hands with AstraZeneca to commercialize certain “ready to use” oncology therapies in China, hoping to capitalize on the UK firm’s strong position in this market.
(Also see "Cellular Stress Targeted By Black Belt TX-Praxis Biotech Partnership" - Scrip, 6 Nov, 2019.)	A strategic partnership active in the hot area of understanding the tumor microenvironment in order to develop new cancer drugs has been formed by two new biotechs, the UK’s Black Belt Therapeutics and the US’s Praxis Pharmaceuticals Inc..
(Also see "Lilly Says Volume Growth Strategy, Launches Working Despite Price Pressures" - Scrip, 30 Apr, 2019.)	Japanese firm signs definitive agreement to acquire Roivant Sciences Inc.'s interests in five “vants” initially, including new gene therapy operation, as ex-Genentech Inc.president named head of new entity.
(Also see "Theramex Buys Janssen’s Evorel Amid Ongoing HRT Shortages " - Scrip, 5 Nov, 2019.)	Amid ongoing manufacturing issues with its own HRT patches, women’s health spinout Theramex  acquires global rights to Janssen Biotech Inc.’s Evorel patches, also in shortage.
(Also see "Alvotech Strikes $45m Deal With Yas Holding" - Generics Bulletin, 5 Nov, 2019.)	Alvotech has struck an investment deal worth $45m with Yas Holding that will give Yas a 2.5% stake in the business, as well as rights to sell three Alvotech biosimilars in the MENA region.
(Also see "Turkey’s Domestic Vaccine Production Drive Prompts New Partnerships" - Scrip, 5 Nov, 2019.)	The Turkish government’s drive to establish domestic manufacturing for vaccines is showing tentative signs of getting off the ground. New partnerships are forming between Turkish and international partners. However, lack of local know-how is hampering progress.
(Also see "Vifor Boosts US Nephrology Prospects With Janssen Pact " - Scrip, 4 Nov, 2019.)	Vifor has boosted its US nephrology prospects with a pact with Janssen to jointly market Invokana in diabetic kidney disease.