Deal Watch: Sanofi Finds Ideal 'Partner' For Leukine

Partner Therapeutics takes on Sanofi's immunostimulant. Novartis transitions struggling Arzerra for compassionate use only outside the US, with compensation to Genmab, while Shire licenses I.V. immunoglobulin candidate from AB Biosciences.

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.

Sanofi Offloads Leukine To Partner Therapeutics

Partner Therapeutics Inc. acquired worldwide rights Feb. 1 to develop, manufacture and commercialize the FDA-approved immunostimulant Leukine (sargramostim) from Sanofi. The Boston-based specialty firm also obtained a dedicated manufacturing facility in Lynnwood, Wash., under the agreement. No specific deal terms were disclosed.

Leukine, which promotes the growth and activation of white blood cells, was contracted by the US Biomedical Advanced Research Authority in 2013 as part of its effort to stockpile medical countermeasures for large-scale emergencies such as a nuclear or radiological event. (Also see "BARDA seeks Amgen's Neupogen, Sanofi's Leukine for nuke attack countermeasures" - Scrip, 27 Sep, 2013.) The agency awarded a $36.5m contract to Sanofi for late-stage development and procurement of Leukine, a recombinant human granulocyte-macrophage colony stimulating (GM-CSF) factor. Simultaneously, BARDA paid Amgen Inc. $157.5m for a larger stockpile of its human GM-CSF product LGF Neupogen (filgrastim).

Cancer-focused Partner noted that Leukine is the only immunomodulatory drug approved by the US FDA to treat acute myelogenous leukemia (AML) in older patients as well as in both allogeneic and autologous bone marrow transplantation. Because Leukine stimulates a broader variety of cells than most growth factors, which are specific to one cell type, the company plans to investigate potential new indications as well as explore ex-US commercial opportunities for the drug.

Partner said the drug is being tested for its potential to improve survival and reduce adverse events in combination with immuno-oncology therapies, including Bristol-Myers Squibb Co.'s Opdivo (nivolumab) and Yervoy (ipilimumab). These include a 250-patient Phase II study testing Leukine combined with Yervoy against Yervoy alone in refractory melanoma and an investigator-sponsored Phase III study testing Leukine with both Bristol products in front-line melanoma.

Leukine also has a pending supplemental biologics licensing application (sBLA) at FDA to add hematopoietic syndrome of acute radiation syndrome (H-ARS) to its label, with a March 29 action date. The application was filed last September and granted priority review by FDA in December.

The manufacturing facility Partner is acquiring was certified for commercial production in 2012 – the company says the site now will serve as its core manufacturing and supply chain center. CEO Robert Mulroy said the deal overall gives Partner "an established commercial business, a product that has demonstrated a clear and substantial impact on outcomes, and a program with the potential to become a core component of immuno-oncology, the treatment of acute radiation syndrome and the treatment of infections."

Novartis To Make Arzerra Compassionate-Use Only Outside US

Novartis AG is to transition the anti-CD20 product Arzerra (ofatumumab) to compassionate-use only for the treatment of certain chronic lymphocytic leukemia (CLL) indications outside the US. It will pay licensor Genmab AS $50m in a lump sum as compensation for lost milestones and royalties.

The product has fallen victim to increased competition in CLL in the last five years; few patients are prescribed Arzerra outside the US. In the EU, Arzerra is approved for the treatment of CLL patients who have relapsed or are refractory to fludarabine and Sanofi's Campath (alemtuzumab), as well as for previously untreated patients for whom fludarabine-based therapy is considered inappropriate due to advanced age and co-morbidities.

Datamonitor Healthcare analysts say Arzerra's uptake likely was impacted by many factors, including use of Biogen Inc./Roche mainstay anti-CD20 product Rituxan (rituximab) as a first-line treatment, an inability to identify Arzerra non-responders, and the drug’s high cost.

Other drugs marketed for CLL include Roche/Biogen's successor anti-CD20 product Gazyva (obinutuzumab), AbbVie Inc./Johnson & Johnson's Imbruvica (ibrutinib), AbbVie/Roche's Venclexta (venetoclax) and Gilead Sciences Inc.'s Zydelig (idelalisib). In addition, more are in late-stage development such as AstraZeneca PLC's Calquence (acalabrutinib), Infinity Pharmaceuticals Inc./Verastem Inc.'s duvelisib and TG Therapeutics Inc.'s ublitiuximab. Rituxan, meanwhile, is facing biosimilar competition.

Novartis is working with regulators to agree a plan for the transition process for ex-US patients currently being treated with the product. Patients accessing the compassionate use program will be offered continued treatment with Arzerra for free as long as they benefit from it.

Genmab will include the $50m in its 2018 guidance to be issued on Feb. 21. Royalties will continue to be earned on net sales of Arzerra.

The two Phase III studies of ofatumumab currently ongoing in relapsing multiple sclerosis and the study of Arzerra in indolent non-Hodgkin's lymphoma will continue, Genmab noted.

Shire Signs IVIg Substitute Pact With AB Biosciences

Shire PLC licensed a very early-stage autoimmune candidate from AB Science on Jan. 30 that the companies hope will prove to be a more effective substitute to currently approved intravenous immunoglobulin (IVIg) therapies.

The deal centers around AB's pan-receptor-interacting molecule (PRIM) program, which uses the firm's oligomeric Fc technology platform and has resulted in a recombinant immunoglobulin product candidate. It has shown encouraging data, including enhanced biological activity, in preclinical models of autoimmune and inflammatory diseases, the partners said.

The companies believe PRIM will offer advantages over current IVIg therapies, which are expensive as they require the traditional plasma collection of thousands of individuals and safety tests. AB added that PRIM offers the potential to be biologically active at lower doses, so non-intravenous routes of administration may be feasible.

Financial terms of the deal were not disclosed but Shire is paying an upfront fee for an exclusive worldwide license to the technology. AB is also eligible for R&D and commercial milestone payments, plus royalties.

The deal represents the first collaboration for Shire to be announced since Andreas Busch took over at R&D chief at the beginning of January, having been poached from Bayer AG. (Also see "Shire Tempts Busch From Bayer As It Eyes Top Spot In Rare Diseases" - Scrip, 1 Dec, 2017.)

The collaboration comes as Shire announced Jan. 8 that it plans to create two distinct divisions within the company – one focused on rare diseases, the other on neuroscience. (Also see "Shire May Split Up – But Punting On Bigger Decisions For Now" - Scrip, 8 Jan, 2018.)

Torrent Buys Its Way Into Controlled Substances

Torrent Pharmaceuticals Ltd. continues its buyout spree – this time buying a pathway into the US controlled substances sector by paying an undisclosed fee for local generics and OTC player Bio-Pharm Inc.

Torrent, which recently snapped up the domestic formulations business of Unichem Laboratories Ltd. for $558m, joins Indian peers like Sun Pharmaceutical Industries Ltd. and Lupin Ltd. that have been keen to play in the high barrier-to-entry controlled substances space. (Also see "No Smoke Without Fire: Unichem Divests Domestic Business To Torrent" - Scrip, 3 Nov, 2017.) (Also see "Sun Starts Integration Of GSK's Opiates Business" - Scrip, 1 Sep, 2015.)

Torrent said that the acquisition announced Jan. 18 is an important step for increasing its US presence, consistent with its strategy of dosage-form diversification, and providing it with new capabilities, including manufacturing and an R&D presence in the US.

Established in 1992, BPI is said to offer a proven track record in the research, development and manufacturing of oral solutions, suspensions and suppositories. BPI's US FDA-registered facility has manufacturing capabilities for controlled substances within US Drug Enforcement Administration (DEA) schedules II to IV. Such products, Torrent highlighted, could only be made in the US under government regulations.

Deals Of The Year

Scrip and In Vivo readers voted in three categories to select the top deals of 2017:

Top Alliance: Regeneron's Novel Deal With Decibel

Regeneron Pharmaceuticals Inc. forged a unique agreement with start-up Decibel Therapeutics in which it will make an equity investment and provide financial support for the hearing-focused biotech's R&D, but claim no share of commercial rights to any therapeutics discovered under the collaboration. (Also see "Novel Regeneron Deal Puts Partner Decibel In The Driver's Seat" - Scrip, 29 Nov, 2017.)

Runner-Up: Medtronic PLC & Aetna Inc.'s outcomes-based insulin pump deal

Top Financing: Pfizer Spins Off SpringWorks

Pfizer Inc. spun out SpringWorks Therapeutics LLC in September with four clinical-stage assets targeting diseases with no good cures. The big pharma concurrently contributed to SpringWorks $103m Series A round, as did Bain Capital Life Sciences, Bain Capital Double Impact, Orbimed and LifeArc. (Also see "SpringWorks Launches With $103m, Four Pfizer Drugs And A Focus On Underserved Patients" - Scrip, 25 Sep, 2017.)

Runner-Up: Silk Road Medical Inc. raises $47m for stroke-prevention devices

Top M&A: J&J/Actelion – Win-Win-Win

Johnson & Johnson's months-long pursuit of Actelion Pharmaceuticals Ltd. culminated in a $30bn cash acquisition last January. J&J got immediate access to the Swiss biotech's lucrative pulmonary arterial hypertension franchise and late-stage pipeline as well as initial 16% ownership in Idorsia Pharmaceuticals Ltd., a new spinout formed around Actelion's drug discovery operations and early-stage clinical assets. (Also see "J&J’s $30bn For Actelion Buys Immediate And Longer-Term Value" - Scrip, 26 Jan, 2017.)

Runner-Up: CVS Health Corp./Aetna vertical merger aims to change health care delivery

To date, BPI had 10 ANDAs approved by the FDA, while 10 others are under review by the agency for the US firm and its partners. Another 17 products are in development. BPI, which is headed by its president, Umakant Shah, currently markets a portfolio of prescription and OTC liquid products including acetaminophen, cetirizine, diphenhydramine, guaifenesin, ranitidine and risperidone oral solutions, along with carbamide peroxide ear drops and oxymetazoline nasal spray. It also offers alternatives to Anusol (hydrocortisone), Dulcolax (bisacodyl) and Preparation H (cocoa butter/phenylephrine) suppositories.

Torrent expects to make further investments to expand the BPI facilities, including research and development capabilities, and increase the number of product filings from BPI. As of September 2017, Torrent had 29 ANDAs pending FDA approval. – Aidan Fry, Generics Bulletin

Ferring Licenses Ligand's OmniAb Antibody Platform

Ligand Pharmaceuticals Inc. licensed worldwide rights Jan. 22 to its OmniAb antibody platform to Ferring Pharmaceuticals AS. OmniAb is a three-species transgenic-animal platform that has four different technologies used to produce mono- and bi-specific human antibodies. The partnership involves the full platform, including OmniRat, OmniMouse, OmniFlic and OmniChicken.

Ferring will make undisclosed annual platform access payments and development and regulatory milestone payments and provide tiered royalties for each product that incorporates the OmniAb antibody platform. (Ferring will also be responsible for all costs).

Sandoz Sells ANDAs To China-Focused CASI Pharmaceuticals

US firm CASI Pharmaceuticals Inc., which focuses on buying products and selling them both at home and in China, acquired on Jan. 26 a portfolio of 25 FDA-approved abbreviated new drug applications (ANDAs) from Novartis' generics division Sandoz Inc.

Details of the deal were minimal and no financials were disclosed, but in additional to the 25 ANDAs, CASI noted that the agreement includes one ANDA that has tentative approval from FDA and three that are still pending approval. The Rockville, Md.-headquartered company, which has a subsidiary and R&D operations in Beijing, said it plans to choose and commercialize some products based on market opportunity and the prospect of cost-effective manufacturing in China and/or the US.

Of the Sandoz ANDAs, CASI's CEO Ken Ren made specific mention of a generic version of Bristol's antiviral Baraclude (entecavir) for hepatitis B, adding that "unfortunately China accounts for more than half of the estimated 700,000 HBV-related deaths worldwide each year." He added that with FDA-approved ANDA status and the high-quality standards of Sandoz, "we anticipate leveraging the Chinese FDA's more recent regulations to accept western pharmaceutical and clinical data for rapid entry into China's market while being competitive in the marketplace."

As for Sandoz, the sale fits with its policy of divesting non-core products. On Jan. 24, the company posted a 17% decline in US sales for the fourth quarter of 2017 – attempts to turn around the business will involve more emphasis on biosimilars and either discontinuing or divesting products, Sandoz CEO Richard Francis told Scrip in an interview. (Also see "Interview: Sandoz CEO On Biosimilars And Reshaping US Business" - Scrip, 25 Jan, 2018.)

Puma Grants Israeli Nerlynx Rights To Medison

Puma Biotechnology Inc. granted Medison Pharma Ltd. exclusive rights on Jan. 30 to sell the breast cancer therapy Nerlynx (neratinib) in Israel. Medison pays money up front, milestones and double-digit royalties and is responsible for obtaining regulatory approval in its territory. Nerlynx obtained FDA approval for US marketing in July 2017, and Medison expects to gain clearance in Israel during the first half of 2019. (Also see "Puma's Nerlynx Scores Broad Label Across Adjuvant Breast Cancer Subgroups" - Pink Sheet, 17 Jul, 2017.)

The product is indicated for adults with early stage HER-positive breast cancer following trastuzumab-based therapy. Puma originally gained rights from Pfizer in 2011. [See Deal] In late 2017, it granted Specialised Therapeutics Asia Pte. Ltd. a license to commercialize the drug in Southeast Asia, including Australia, Singapore, Malaysia, Brunei and New Zealand. [See Deal]

Medison’s portfolio encompasses a variety of disease areas including neurology, oncology, kidney disease, cardiology, blood disorders and infectious diseases. Earlier in January, the company gained exclusive Israeli rights to Resverlogix Corp.’s apabetalone, a BET inhibitor in development for high-risk cardiovascular disease patients with atherosclerosis/hypercholesterolemia and type 2 diabetes, chronic kidney disease, Alzheimer's, Fabry's, macular degeneration, HIV, paroxysmal nocturnal hemoglobinuria and facioscapulohumeral muscular dystrophy. [See Deal]

CJ Healthcare Grants Chinese EPO Biosimilar Rights To NCPC GeneTech

South Korea's CJ Healthcare Corp. said on Jan. 31 that it has agreed to license out its second-generation erythropoietin (EPO) biosimilar's rights in China to NCPC GeneTech Biotechnology.

Under the agreement, the Chinese company will have the exclusive right to proceed with clinical trials, approval, production and sales of CJ-40001 (darbepoetin alpha), CJ Healthcare's version of Kyowa Hakko Kirin Co. Ltd.'s NESP/Aranesp, in China. Financial terms weren't disclosed.

CJ Healthcare's second-generation EPO biosimilar has reduced administration times to once or twice a week from the first generation EPO product's three times a week administration. It is used for the treatment of anemia.

The longer-lasting biosimilar also was licensed out to Japan's YL Biologics Ltd. in September last year to enter the Japanese market.

CJ expects the Chinese market for the second-generation EPO products to reach about KRW300bn ($281m) once they are launched. NCPC, which is showing strength in the Chinese EPO market, is expected to grab about KRW100bn of the market annually. "Starting with China, we plan to expand our territories to other countries including Southeast Asia as well as Central and South America," said CJ Healthcare CEO Seok-Hee Kang.

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

(Also see "Seattle Genetics Diversifies Beyond ADCs With Cascadian Acquisition" - Scrip, 31 Jan, 2018.)	Seattle Genetics Inc. already was looking to move into solid tumors, particularly breast cancer, with its ADCs, but now will take over a promising oral candidate in pivotal studies in HER2-positive breast cancer.
(Also see "Mysterious Amazon/Berkshire/JPMorgan Partnership Could Disrupt Health Care, Pharma" - Scrip, 30 Jan, 2018.)	The collective bargaining power of the three large employers, potentially assisted by [Amazon.com Inc.]'s low-cost distribution channels, could be a formidable force in negotiating lower cost and better quality health care services, including pharmaceutical products.
(Also see "Ablynx, Bioverativ Buys Drive Sanofi's Hematology Reign" - Scrip, 29 Jan, 2018.)	Sanofi's €3.9bn acquisition of Ablynx NV will allow the French big pharma to build up its rare blood disorder pipeline and bring in complementary programs in areas like respiratory infections.
(Also see "A Deal For Biogen, But Not The One Investors Are Waiting For" - Scrip, 25 Jan, 2018.)	Biogen announced a small deal with Karyopharm Therapeutics Inc. for a preclinical asset with potential in ALS, but large deals are also being considered, management told the fourth quarter earnings call.
(Also see "Novartis’s Luxturna Deal Expands Gene Therapy Ambitions" - Scrip, 25 Jan, 2018.)	By licensing Spark Therapeutics Inc.' Luxturna outside the US, Novartis is expanding its gene therapy ambitions into in vivo and non-oncological treatments.
(Also see "Panacea-Serum Team Up To Take Six-In-One Vaccine Global" - Scrip, 23 Jan, 2018.)	Panacea Biotec Ltd. has allied with the world’s largest-vaccine maker, the Serum Institute of India Ltd., to ramp up production of a six-in-one jab aimed at preventing killer diseases like polio and diphtheria and target a global market estimated to be worth over $1.25bn annually.
(Also see "Celgene Seeks CAR-T Leadership, Hematology Diversification With Juno Buy" - Scrip, 22 Jan, 2018.)	Celgene will pay $9bn to buy the 90.3% of Juno Therapeutics Inc. that it doesn't already own, seeking to not only become a leader in the CAR-T field, but to increase its leadership in non-Hodgkin lymphoma, multiple myeloma, other hematological malignancies.
(Also see "Sanofi Builds Blood Disorder Specialty With Bioverativ Buy" - Scrip, 22 Jan, 2018.)	The French drug maker is making a big splash into blood disorders with the $11.6bn acquisition of hemophilia specialist Bioverativ Inc.Eloctate and Alprolix are young and growing brands, but the competition in hemophilia is fierce, which means Bioverativ's pipeline will also need to deliver to justify the premium price.
(Also see "Dong-A Ties With NeuroBo For Diabetic Neuropathy, Alzheimer's" - Scrip, 19 Jan, 2018.)	Dong-A ST Co. Ltd. makes notable progress in botanical drug programs, reaching deals for its diabetic neuropathic pain and Alzheimer's disease drug assets with Boston-based NeuroBo Pharmaceuticals.
(Also see "Better Together: BioCryst, Idera Merge To Improve Rare Disease Position" - Scrip, 22 Jan, 2018.)	New company will have pair of Phase III candidates, an immuno-oncology licensing opportunity, strong experience in hereditary angioedema and roughly $243m in cash to position itself as a rare disease stronghold.
(Also see "Riding The Next Wave Of Biosimilars: Sandoz To Link Up With India's Biocon" - Scrip, 18 Jan, 2018.)	Pooling resources appears key to a major new collaboration in the biosimilars space, between Sandoz and India's Biocon Ltd., to develop the next generation of biosimilar immunology and oncology products.