Deal Watch: Astellas/Cytokinetics Extend Partnership, Make Progress On SMA Candidate

The two firms hope improvement in the six-minute walk test might be accepted by the US FDA as registrational endpoint for reldesemtiv in spinal muscular atrophy. Blackstone acquires Clarus, while Merck licenses TriNKETs from Dragonfly.

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.

Astellas/Cytokinetics Extend Their Collaboration Through 2019

Partnered since 2013 to co-develop Cytokinetics Inc.’s small molecule troponin activators, the South San Francisco biotech and Japanese pharma Astellas Pharma Inc. announced Oct. 5 that they have extended their joint research collaboration through the end of 2019. The pair signed two-year extensions to the partnership in 2015 and 2017.

In addition to updating the status of their lead candidate reldesemtiv (CK-2127107), a fast skeletal muscle troponin activator (FSTA), in several indications, the companies also said they are advancing a new FSTA candidate into investigational new drug (IND)-enabling studies, triggering a $2m milestone payment from Astellas to Cytokinetics.

The partners also announced progress on reldesemtiv in spinal muscular atrophy; they are seeking a Type C regulatory meeting with the US FDA to inquire about the suitability of the six-minute walk test as primary endpoint in a registrational program. In June, Cytokinetics and Astellas reported data from a Phase II study in which the reldesemtiv showed statistically significant, concentration-dependent increases in change from baseline on the six-minute walk test compared to placebo.

In late 2017, the firms switched focus to reldesemtiv after their first-generation candidate, tirasemtiv, failed to meet any primary or secondary endpoints in the Phase III VITALITY-ALS study in amyotrophic lateral sclerosis. (Also see "With Phase III Failure, Cytokinetics Shelves Tirasemtiv, Pivots To ALS Backup" - Scrip, 21 Nov, 2017.) The ongoing FORTITUDE-ALS study has enrolled 350 of a planned 445 patients to date, with enrollment expected to finish during the fourth quarter and initial results from the ALS trial reading out during the first half of 2019.

Meanwhile, the companies reported that an Astellas-run Phase II study in chronic obstructive pulmonary disease did not meet its primary endpoint nor did it show a statistically significant treatment difference on any secondary endpoints.

Cytokinetics and Astellas inked their agreement in June 2013, with Astellas paying $16m up front plus $24m in R&D funding. [See Deal] The deal also outlined potential for up to $450m in pre- and post-commercial milestones payments to Cytokinetics.

Blackstone Officially Moves Into Life Sciences With Clarus Buyout

Blackstone announced Oct. 4 that it is acquiring the life sciences investment firm Clarus at undisclosed terms and launching Blackstone Life Sciences, which the New York investment firm said will fill a “critical void” by investing across the lifecycle of companies and products across key life science sectors. The deal is expected to close in the fourth quarter.

Based in both Boston and San Francisco, Clarus has raised roughly $2.6bn since its inception in 2005, most recently leading a $70m Series C round and $80m royalty agreement for Galera Therapeutics Inc., which simultaneously arranged an $80m royalty deal based on investor optimism for its lead candidate, the Phase III small molecule dismutase mimetic for severe oral mucositis in head-and-neck cancer patients receiving radiation therapy. (Also see "Galera Raises $150m To Take Lead Drug From Phase III To NDA Submission" - Scrip, 19 Sep, 2018.)

The agreement specifies that Nick Galakatos, currently managing director of Clarus, will become head of Blackstone Life Sciences. The company’s goal will be to partner with major biopharmaceutical companies to give them the capital and operating expertise needed to expand their R&D budgets and bring their therapeutic candidates to market, said Joe Baratta, global head of private equity at Blackstone. He added that Clarus’ existing business focus is consistent with Blackstone’s investment philosophy across various business sectors.

Merck Options Rights To Dragonfly’s Immuno-Oncology Compounds

Dragonfly Therapeutics Inc. granted Merck & Co. Inc. an option Oct. 1 to license exclusive rights to cancer compounds discovered using Dragonfly’s TriNKET technology. TriNKETs (Tri-specific NK cell Engagement Therapies) bind to proteins expressed on cancer cells and natural killer (NK) cells, and activate NK cells to attack tumors as well as to initiate an immune response that prompts T- and B-cells to also act against the cancer.

Merck will pay up to $695m in upfront and milestone payments per resulting project, plus sales royalties. The deal is the second of its kind for Dragonfly. The three-year-old biotech penned an agreement with Celgene Corp. last year under which Celgene paid $33m up front and holds an option to license rights to up to four TriNKETs for acute myeloid leukemia, multiple myeloma and other blood cancers. [See Deal]

Roche Licenses Global Rights To Go Antibody Candidate

Boston-area biotech Go Therapeutics Inc. granted a worldwide exclusive license Oct. 2 to Roche to antibodies addressing a novel, cancer-specific target generated with Go’s glycoproteomic platform. The biotech gets $9m in upfront fees and near-term milestones under the agreement, with the potential to earn up to $186m in additional milestones as well as mid-single to low-double-digit sales royalties should a product reach market.

Go CEO Constantine Theodoropulos said his company’s glycotargeting bispecific antibody candidates can “help widen the therapeutic window” for a variety of cancer therapies, including T-cell bispecific antibodies, chimeric antigen receptor T-cell (CAR-T) therapeutics and antibody-drug conjugates (ADCs).

The biotech’s candidates are immune-redirected therapies that target tumor-specific antigens, he added. In preclinical study, they’ve demonstrated specificity in targeting solid tumors rather than normal tissue with a clean in-vivo toxicology profile.

Kite Partners With HiFiBio On TCR Screening

Gilead Sciences Inc. subsidiary Kite Pharma Inc. signed a research collaboration and licensing agreement with HiFiBio Therapeutics Oct. 2 to develop technology that will support Kite’s discovery and development efforts for antigen-reactive T-cell receptor (TCR) therapeutics for cancer. Paris-headquartered HiFiBio gets $10m up front and can earn undisclosed research milestones under the agreement.

The French biotech, which also has locations in Cambridge, Mass., and Shanghai, focuses on antibody discovery through single B-cell screening and analysis. The partners will apply HiFiBio’s proprietary single-cell technology platform to provide high-throughput screening of TCR repertoires from patient samples to identify shared antigen and neoantigen TCRs that could be used in therapeutic applications. The companies noted that neoantigens discovered under this process might offer the potential for more targeted anti-tumor activity.

Kite gets an exclusive option under the deal to license HiFiBio’s platform for the screening work and to identify TCRs for use in targeted engineered T-cell therapies. Kite said the partnership will add to its capabilities in discovering cell therapies to target individual patient’s tumor neoantigens.

Decibel Licenses Oricula’s Phase I Hearing Loss/Balance Disorder Drug

Decibel Therapeutics exclusively licensed Oricula Therapeutics LLC's ORC13661, a Phase I oral drug for the prevention of hearing loss and balance disorders following the treatment of severe infections with aminoglycoside antibiotics, on Sept. 27.

ORC13661 is a new chemical entity being tested for the prevention of ototoxicity that works by blocking aminoglycosides from entering into hair cells in the inner ear. Patients at particular risk for ototoxicity include those treated for pulmonary exacerbations from cystic fibrosis, non-tuberculous mycobacterial infections, multidrug-resistant tuberculosis and endocarditis.

The compound originated from a research agreement between the University of Washington and the Fred Hutchinson Cancer Research Center and was in-licensed by Oricula in 2013.

Eyevance Gets Global Rights To Nexagon From OcuNexus

OcuNexus Therapeutics Inc. licensed Eyevance Pharmaceuticals LLC worldwide rights on Oct. 2 to develop and commercialize its ophthalmic candidate Nexagon topical gel. Nexagon is a Phase III antisense oligodeoxynucleotide being developed for persistent corneal epithelial defect (PED).

The therapy is designed to inhibit connexin43 (Cx43), which is a cell membrane hemichannel forming protein that is overexpressed following acute injury or in chronic disease. Nexagon works by promoting regeneration of the corneal epithelium. It’s the first ophthalmic drug in development that targets Cx43 and the inflammasome pathway of inflammation. Eyevance expects to commence a pivotal trial in the first quarter of 2019.

In September, Eyevance acquired global rights to Focus Laboratories Inc.’s FreshKote lubricant eye drops. [See Deal]

Menarini Obtains Rights To Three Melinta Antibiotics

Melinta Therapeutics Inc. licensed Menarini Group exclusive rights Oct. 1 to co-develop and commercialize three antibiotics in 68 countries in Europe; Asia-Pacific territories (excluding Japan) that include China, South Korea and Australia; and the Commonwealth of Independent States including Russia. Menarini will make an upfront payment to Melinta, in addition to regulatory and sales milestones and royalties. The deal is worth up to $265m.

The three US marketed drugs are: Vabomere (meropenem/vaborbactam) for urinary and respiratory tract infections, Orbactiv (oritavancin) for skin and skin-structure infections caused by Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, and Minocin (minocycline) for infections due to susceptible strains of several Gram-positive and Gram-negative pathogens. Melinta acquired all three via its November 2017 acquisition of The Medicines Co.’s infectious disease business for $270m. [See Deal]

In September, the EMA’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending Vabomere for approval as a treatment for adults with complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia including ventilator-associated pneumonia, bacteremia that occurs in association with any of these infections, and infections due to aerobic Gram-negative organisms where treatment options are limited. (Also see "EU Approval Set For Three New Orphans And Lilly’s Emgality; Exondys Appeal Fails" - Pink Sheet, 24 Sep, 2018.)

In a similar deal signed last year, Melinta licensed Menarini exclusive rights to develop and commercialize the fluoroquinolone Baxdela (delafloxacin) in the same 68 territories as the current tie up. [See Deal]

Pfizer To Sell Bioventus' Durolane In Brazil

Pfizer Inc. acquired exclusive rights Oct. 2 to distribute Bioventus Inc.’s osteoarthritis (OA) product Durolane (hyaluronic acid) in Brazil. The deal is concurrent with Durolane receiving marketing approval from Brazilian regulators.

The product is a single-injection, joint-fluid therapy for mild-to-moderate knee and hip OA. Durolane is designed to manage osteoarthritic pain by using stabilized hyaluronic acid, a naturally occurring molecule that lubricates and cushions the joint. Pfizer’s over 100-strong sales team in Brazil will sell the product alongside its other arthritis drugs, including Celebra (celecoxib).

Taro Ends NovaBiotics Pact After Novexatin Failure

Taro Pharmaceutical Industries Ltd. has ended a global licensing deal signed in 2013 with NovaBiotics Ltd. for the latter’s investigational antifungal nail treatment. [See Deal] The Israeli firm terminated the agreement after the product, Novexatin (NP213), failed to show superiority over placebo in a 184-patient Phase IIb study conducted at multiple sites in the US.

Novexatin was generated by Scotland-based NovaBiotics’ rational drug-design platform for antimicrobial peptides (AMPs). (Also see "Cystic Fibrosis: NovaBiotics Advances Old Dog With New Tricks" - Scrip, 16 Jul, 2018.) It is a novel cationic antifungal peptide that was formulated as a topical, brush-on treatment for onychomycosis. Novabiotics’ pipeline also includes Lynovex for cystic fibrosis-associated lung disease, the antibiotic potentiator/resistance breaker Nylexa, and additional early-stage antifungal and antibacterial candidates derived from its AMP platform, including Novamycin and Novarifyn.

Sanofi, AstraZeneca Complete Announced Divestments

Sanofi has completed the €1.9bn divestment of its European generics business to the private equity group Advent International. (Also see "Sanofi Finalizes Zentiva Sale With Focus Back On Turnaround" - Scrip, 28 Jun, 2018.)

AstraZeneca PLC has completed the sale of European rights to its Atacand (candesartan cilexetil) and Atacand Plus (candesartan cilexetil/hydrochlorothiazide) brands to Germany’s Cheplapharm Arzneimittel GMBH. It received $200m and stands to receive a time-bound payment of $10m plus sales-based milestones. The two products, to treat heart failure and hypertension, generated sales of $86m in Europe in 2017. (Also see "Deal Watch: LEO Pharma Expands Market Reach Through Bayer Dermatology Deal" - Scrip, 31 Jul, 2018.)

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

(Also see "J&J Bets Big On Arrowhead’s Early Promise In Hepatitis B" - Scrip, 4 Oct, 2018.)	Johnson & Johnson is paying $250m up front for worldwide rights to Arrowhead Pharmaceuticals Inc.’s Phase I/II RNAi candidate. Arrowhead says letting J&J take the lead on HBV enables it to focus on other pipeline programs it can bring to market itself.
(Also see "Aduro Says End Of Janssen Collaborations “Not A Lethal Blow”" - Scrip, 3 Oct, 2018.)	Both Janssen Pharmaceuticals Inc. and Aduro BioTech Inc. gradually realized the Listeria technology platform was not delivering hoped-for results. Aduro will not continue the projects abandoned by Janssen, and will focus on its STING and APRIL programs going forward.
(Also see "Boston Bags Assets From GSK and Novartis" - Scrip, 3 Oct, 2018.)	The US firm is getting its hands on eight programs from two of the world's leading drug makers, seeing an opportunity in areas such as antibiotics where solutions may be more likely to come from biotech rather than big pharma.
(Also see "Momenta Is Exiting Biosimilars; Is That A Bellwether For Biosimilar Sentiment? " - Scrip, 2 Oct, 2018.)	Momenta Pharmaceuticals Inc. CEO Craig Wheeler talked to Scrip about the challenging biosimilar market dynamics and the company's decision to end most biosimilar drug development. The path to value creation in biosimilars is not clear, he said.