Deal Watch: Vertex Selects First Candidate Under CRISPR Gene-Editing Collaboration

Vertex hopes to develop CTX001 as a treatment for sickle cell disease and beta thalassemia. Allergan adds stalled uterine fibroid candidate in buyout of troubled Repros, Juno licenses multiple myeloma candidate from Lilly.

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.

Vertex Licenses Hemoglobinopathy Candidate Under CRISPR Deal

Under their 2015 research agreement giving Vertex Pharmaceuticals Inc. option rights on up to six candidates, the Cambridge, Mass.-based firm has licensed CTX001 from CRISPR Therapeutics for the treatment of hemoglobinopathies, including sickle cell disease and beta thalassemia. The licensing fee was not disclosed in the Dec. 12 announcement, but the two companies will equally share all global research and development costs and profits under a co-development and co-commercialization arrangement.

Vertex paid $105m up front ($75m in cash, plus a $30m equity stake in CRISPR) for the initial collaboration to evaluate the use of the CRISPR-Cas9 gene editing platform across multiple disease targets. The agreement also specified that Vertex would fund the partnership's discovery activities, to be conducted mainly by CRISPR. The gene-editing firm is eligible for up to $420m in development, regulatory and sales milestones for each program under the collaboration. [See Deal]

The agreement specifies that CRIPSR will lead US commercialization for hemoglobinopathy therapies resulting from the collaboration, while Vertex will lead ex-US commercial activity for those products and hold all commercial rights to partnership assets outside of hemoglobinopathy. The 2015 partnership initially focused on using Cas9 to correct mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and edit other genes that contribute to cystic fibrosis; Vertex has a portfolio of products focused on CFTR.

An EU Clinical Trial Application was submitted earlier in December for CTX001 to support initiation of a Phase I/II trial in beta thalassemia in 2018 in Europe, while an Investigational New Drug (IND) application to the FDA is planned for 2018 to support a Phase I/II trial in sickle cell disease in the US. Preclinical data for CTX001 presented at the American Society for Hematology conference on Dec. 10 showed greater than 90% editing of hematopoietic stem cells at the target site, leading to clinically relevant increases in fetal hemoglobin that the companies say support the advancement of CTX001 into clinical development.

Otsuka Gives Up On GW's Cannabinoid

GW Pharmaceuticals PLC has reacquired the US rights to its cannabinoid Sativex (nabiximols) from Otsuka Pharmaceutical Co. Ltd. "without making any upfront payment to Otsuka," the firm said, though it has agreed to pay milestone payments if Sativex is approved by the US FDA and if the drug achieves certain annual sales thresholds. The companies announced the termination of a 2007 licensing agreement on Dec. 13. [See Deal]

GW, describing the split as amicable, noted that it has previously conducted positive Phase II and III trials with the drug. However, the clinical trials in treatment of cancer pain conducted under the partnership did not meet the primary endpoint. (Also see "Cannabis Derivative Sativex 'Shows Promise In US Patients' Despite Further Phase III Failure" - Scrip, 29 Oct, 2015.) An oromucosal spray of a formulated extract that contains the cannabinoids cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), GW reports that Sativex is approved in 29 countries outside the US for treatment of spasticity in patients with multiple sclerosis.

Allergan To Buy Repros And Stalled Uterine Fibroid Candidate

Allergan PLC agreed to pay about $26.4m to acquire cash-poor Texas biotech Repros Therapeutics Inc. on Dec. 12, bringing the specialty pharma a Phase IIb candidate for uterine fibroids that is stalled by an FDA request for substantial safety data before it can begin Phase III testing. Under the agreement, Allergan will pay $0.67 per share for all outstanding shares (roughly 39.56m) in Repros, which finished the trading day at $0.47 on Dec. 11.

Telapristone acetate (provisional brand name Proellex) is an orally active, selective progesterone receptor modulator that reached Phase IIb in uterine fibroids, before FDA placed the compound on a partial clinical hold due to liver toxicity concerns. Repros lacked the finances the complete the required safety study – it reported $1.8m cash on hand as of Sept. 30, 2017.

Allergan already has a uterine fibroid therapy on the market in Esmya (ulipristal acetate). There are seven drugs in clinical development for uterine fibroids, including Bayer AG's vilaprisan, a Phase III oral, selective progesterone receptor inhibitor. Takeda Pharmaceutical Co. Ltd. and Myovant Sciences Ltd. are competing with AbbVie Inc. and Neurocrine Biosciences Inc. to bring the first oral gonadotropin-releasing hormone receptor (GnRH) antagonist to market for this indication, with Phase III candidates relugolix and elagolix, respectively. (Also see "Takeda Paves The Way For Myovant With Phase III Fibroid Success" - Scrip, 3 Oct, 2017.)

Juno Licenses Multiple Myeloma Candidate From Lilly

Eli Lilly & Co. granted Juno Therapeutics Inc. rights Dec. 6 to its gamma-secretase inhibitor LY3039478, which Juno will investigate as a treatment for multiple myeloma. Financial terms were not disclosed.

Lilly has the candidate in Phase II trials for T-cell lymphoma and acute lymphocytic leukemia, as well as Phase I for solid tumors, but Juno is interested in implications the compound may have for myeloma when combined with B-cell maturation antigen (BCMA)-directed CAR T cells. Research has shown that gamma-secretase inhibitors can increase surface expression of BCMA on tumors, including myeloma, and could increase the strength of BCMA-directed CAR-T therapy.

Juno hopes to have a GSI/BCMA CAR-T candidate in clinical trials next year; it is currently recruiting patients for a Phase I trial of its BCMA-directed CAR-T in combination with the chemo drug Revlimid (lenalidomide). Concurrent with the Lilly deal, the company also licensed GSI/BCMA intellectual property from biomarker firm OncoTracker Inc. and the Fred Hutchinson Cancer Research Center. [See Deal]

Ono And Cyclenium Collaborate On Macrocycle Discovery Effort

Ono Pharmaceutical Co. Ltd. signed a drug discovery collaboration Dec. 12 with Cyclenium Pharma Inc., to use the latter's QUEST Library platform to generate novel, synthetic small molecule macrocycle candidates against pharmacological targets specified by the Japanese pharma. No specific financial terms were revealed, but Cyclenium will get an upfront payment and research funding, and be eligible to earn development milestones and sales royalties under the deal.

Based in Montreal, Cyclenium will be responsible for medicinal chemistry work under the partnership, including hit validation, while Ono will use its internal capabilities to characterize the discoveries for biological and pharmacological properties. Ono gets full worldwide development and commercial rights to the resulting drug candidates.

Arena, Everest Team To Develop Two Drugs In Asia

Arena Pharmaceuticals Inc. entered into a development and commercialization partnership on Dec. 5 with Chinese Everest Medicines Limited to develop ralinepag and etrasimod in mainland China, Taiwan, Hong Kong, Macau and South Korea.

Under the collaboration with Arena, Everest is responsible for funding development and commercialization in the specified territories. In exchange for exclusive rights, Everest will make an upfront payment of $12m to Arena, with additional milestone payments up to $212m and low double-digit royalties on net annual sales of both drugs.

Both drugs were discovered and developed by Arena internally. Currently, ralinepag (APD811), an oral and selective prostacyclin receptor (IP) agonist for the treatment of pulmonary arterial hypertension (PAH), has finished Phase II studies and is readying to enter Phase III. (Also see "Arena Rises, But Raises Questions With Phase II Ralinepag Data In PAH" - Scrip, 11 Jul, 2017.) Meanwhile, etrasimod (APD334), an oral and selective sphingosine-1-phosphate (S1P) receptor modulator, is under evaluation for multiple autoimmune diseases in Phase II, including ulcerative colitis, pyoderma gangrenosum and primary biliary cholangitis. (Also see "Deal Watch: Taking Care Of Business Before J.P. Morgan" - Scrip, 6 Jan, 2017.)

Arena said China’s new regulations to expedite approvals could bring significant opportunity for both drugs in early synchronization of development. Everest’s veteran leadership team would also be able to rapidly advance these two highly differentiated investigational drugs towards approval and launch in China under the evolving regulatory landscape.

Based in Shanghai, Everest focuses on developing late-stage pharmaceuticals through licensing. The company has completed a Series A financing of $130m, led by C-Bridge Capital with an investment of $50m. C-Bridge currently has $700m in assets under management; its investment portfolio of companies includes Ascletis Inc. and I-MAB Biopharma.

Almirall Licenses Actinic Keratosis Candidate From Athenex

Spain's Almirall SA will pay $55m in upfront and near-term costs to in-license Phase III dermatology candidate KX2-391 from Buffalo-based Athenex Inc. Announced Dec. 11, the deal gives Almirall development and commercialization rights in the US and Europe, including Russia, for the first-in-class dual Src kinase and tubulin polymerization inhibitor being developed as a topical therapy for actinic keratosis and other skin indications.

Under the agreement, Athenex can earn up to $65m in milestone payments tied to launch and development of the candidate in other indications, as well as sales milestones up to $155m. The biotech is eligible for additional milestone payments if sales exceed projections, as well as tiered net sales royalties starting at 15%.

Boston Biotechs Collaborate On Living Probiotic Medicines

Ginkgo Bioworks and Synlogic Inc. announced Dec. 8 that they will collaborate to build a discovery engine for novel, living medicines to treat neurologic and liver disorders. No financial terms were disclosed.

The partnership will combine Synlogic's discovery and development capabilities around novel Synthetic Biotic medicines – engineered probiotics designed to perform metabolic conversions in a patient's gut that can replace missing or damaged physiological processes – with Ginkgo's expertise in high-throughput organism screening and design, the companies say. (Also see "Synlogic Moves Synthetic Biotics To The Clinic For Rare Metabolic Disease" - Scrip, 30 Oct, 2017.)

The partnership's focus will be on combining the firms' optimization capabilities, establishing a working model for a joint discovery engine and generating drug leads for a broad range of neurological and liver conditions. Further along, the two companies will seek partners for portfolio expansion, clinical development and commercialization of resulting drug candidates.

Xynomic, Janssen Team Up In Lymphoma Trial Collaboration

Xynomic Pharmaceuticals Inc. and Janssen R&D LLC are partnering to evaluate Xynomic's abexinostat with Janssen's ibrutinib for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) or relapsed/refractory mantle cell lymphoma (r/r MCL). Under a collaboration announced Dec. 1, the Phase I/II trial will be led by Memorial Sloan Kettering Cancer Center researchers Anita Kumar and Anas Younes to assess the combination of the two compounds in r/r DLBCL or r/r MCL in addition to studying the biologic predictors of response and resistance to dual BCR and HDAC inhibition.

Abexinostat is in Phase II for various lymphomas (DLBCL, MCL, non-Hodgkin's, Hodgkin's, follicular and cutaneous and peripheral T-cell), soft tissue sarcoma, chronic lymphocytic leukemia, colorectal cancer, and myeloma, and in preclinical studies for renal cancer. Ibrutinib is sold as Imbruvica by Janssen Pharmaceuticals Inc. and Pharmacyclics Inc. for MCL, chronic lymphocytic leukemia, Waldenstrom's hypergammaglobulinemia and graft-versus-host disease. It is also being studied in Phase III for multiple lymphomas and pancreatic cancer; in Phase II for B-cell lymphoma, myeloma and breast, non-small cell lung, renal, colorectal, stomach and genitourinary cancers.

China's HitGen Inks Drug Discovery Partnership With BI

HitGen Ltd. entered into a drug discovery collaboration Nov. 27 to identify novel small molecules for targets of interest to Boehringer Ingelheim GMBH. While specific financial details of the agreement were not disclosed, BI agreed to make upfront payments and milestones to the Chinese biotech resulting from any licensing activity.

HitGen will use its technology platform based on DNA-encoded library design and synthesis and screening to find the leads for BI. The company's DNA-encoded chemical libraries contain more than 90bn novel, diverse, drug-like small-molecule and macrocycle compounds.

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

(Also see "Gilead Acquisition Of Cell Design: The Next Logical Step" - Scrip, 8 Dec, 2017.)

Already partnered with Kite Pharma Inc. to apply two technology platforms to CAR-T candidates, Cell Design Labs Inc. adds to Gilead Sciences Inc.'s immuno-oncology expertise. Analysts expect more add-ons for Gilead's increasing IO focus.

(Also see "Hisun-Pfizer Split: What Went Wrong And What Next?" - Scrip, 8 Dec, 2017.)

The breakup of the Hisun-Pfizer Pharmaceuticals Co. Ltd. JV typifies an unhappy marriage between Chinese and MNC pharma firms in the generics segment in recent years, although the two companies will continue to work as commercial partners under a new framework. Scrip delves into the reasons for the split and also outlines why China is, nevertheless, expected to see more joint ventures for innovative drugs.