Deal Watch: Bristol Leaves Neuropathic Pain Candidate To Lexicon

Verastem steps in where AbbVie exited, agreeing to license Infinity’s duvelisib in hematologic cancer indications. Celldex grows its immuno-oncology pipeline with buyout of private Yale Medical School-spinout Kolltan.

Scrip regularly covers business development and deal-making in the biopharmaceutical industry. Below is a roundup of some of the most noteworthy transactions that occurred between Oct. 31-Nov. 8. Deal Watch is supported by deal intelligence from Strategic Transactions.

Lexicon Paying Bristol To Take Over Neuropathic Pain Candidate

In an amendment to their 2003 neuroscience R&D collaboration, Lexicon Pharmaceuticals Inc. and Bristol-Myers Squibb Co. have agreed that the former will take over development of neuropathic pain candidate LX9211 (formerly BMS-986176). The small molecule is currently completing IND-enabling studies and Lexicon plans to bring it into the clinic in 2017.

The agreement announced Nov. 7 does not include any upfront cash, but Lexicon will pay Bristol development and regulatory milestones in exchange for exclusive development and commercial rights to the candidate, starting with the commencement of Phase II.

The move follows Bristol’s recent announcement that it was undertaking various cost-control measures, now that its immuno-oncology portfolio is under pressure. (Also see "Bristol Stresses Cost Control Despite Strong Earnings Quarter" - Scrip, 27 Oct, 2016.) Neuroscience is not one of Bristol’s “R&D areas of focus.”

Lexicon, which applied its gene-knockout technologies to discover novel targets under the partnership, said it earned $86m in milestones during the alliance’s target discovery portion, which ended in October 2009. [See Deal] The two continued working together, however, on neuroscience drug candidates resulting from that work and selected LX9211 as their lead candidate from the alliance in April 2015.

The Woodlands, Texas-based company also gets exclusive rights to other small molecules that act through the same target as LX9211, although the target is not being disclosed. Lexicon said the candidate has shown robust efficacy in models of neuropathic pain and has been well-tolerated at efficacious and larger doses in animals.

Bristol also can earn milestone payments for development of second and third indication for LX9211 under the agreement, as well as royalties on sales if the candidate reaches market and certain sales-based milestones.

Verastem Expands Oncology Profile With Infinity’s Duvelisib

US based Verastem Inc. and Infinity Pharmaceuticals Inc. announced a license agreement Nov. 2 in which Verastem acquires exclusive worldwide rights to develop and commercialize Infinity's duvelisib, an oncology candidate that inhibits the enzymes phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma.

The drug candidate, dropped by AbbVie Inc. in June after a two-year collaboration with Infinity, is being developed for the treatment of hematologic cancers, including chronic lymphocytic leukemia (CLL), indolent non-Hodgkin lymphoma (iNHL) and T cell lymphomas. (Also see "Deal Watch: Merck Hopes Moderna's Personalized Vaccines Can Increase Keytruda Patient Base" - Pink Sheet, 4 Jul, 2016.)

Just over a week ago, Roche’s Genentech Inc. made its own move to get out of the crowded PI3K field, out-licensing its GDC-0084 to Novogen Ltd. (Also see "Deal Watch: Genentech Out-Licenses PI3K Inhibitor To Novogen" - Scrip, 31 Oct, 2016.)

Duvelisib is currently being studied in late- and mid-stage clinical trials including DUO, a randomized Phase III monotherapy study in patients with relapsed/refractory CLL for which results will be presented in the first half of 2017. Recently, the compound completed a Phase III monotherapy study, DYNAMO, in patients with refractory indolent non-Hodgkin lymphoma (iNHL), successfully meeting the primary endpoint but producing still disappointing results that led to AbbVie’s departure from co-development. (Also see "Infinity Doesn't Sugarcoat Disappointing Duvelisib Data; Cuts R&D Staff To Preserve Cash" - Scrip, 15 Jun, 2016.)

Under the agreement, announced Nov. 2, there will be no upfront payment; however, Verastem will pay Infinity up to $28m in milestones and the first milestone payment of $6m will be triggered by positive data from the DUO study. [See Deal] Infinity is also entitled to receive $22m after the first regulatory approval inside or outside of the US and will be paid royalties on net sales by Verastem.

Duvelisib works in two ways; it can either attack the cancer directly and or disrupt the tumor microenvironment by inhibiting PI3K-delta and PI3K-gamma, enzymes that usually support the growth and survival of malignant B-cells and T-cells. Activation of PI3K results in the growth of malignant B-cells, potentially having a part in the formation and maintenance of the supporting tumor microenvironment.

Verastem already holds rights to the focal adhesion kinase (FAK) inhibitors defactinib (VS-6063), currently being studied in separate clinical collaborations with Merck & Co. Inc. and Pfizer Inc./Merck KGAA[See Deal], and VS-4718. The company believes duvelisib “is a compelling strategic fit that complements our existing pipeline – which also targets modulation of tumor microenvironment."

Celldex Adds To Cancer Pipeline With Buyout Of Kolltan

Celldex Therapeutics Inc. acquired privately held Kolltan Pharmaceuticals Inc. Nov. 2 by issuing $62.5m in new stock. Kolltan also could earn up to $172.5m in earn-outs based on development, regulatory and sales achievements by its pipeline assets. [See Deal]

Kolltan is developing antibody-based drugs targeting receptor tyrosine kinases; the goal is to develop treatments that overcome tumor resistance associated with currently available tyrosine kinase inhibitors.

Celldex gets a pipeline that includes KTN01058, a KIT activation inhibitor in Phase I for gastrointestinal stromal tumors; KTN3379, an ErbB3 (HER3) inhibitor in-licensed from MedImmune LLC[See Deal] currently in Phase I for head-and-neck squamous cell carcinoma; and a TAM program (candidates that modulate the Tyro3, Axl and MerTK kinases).

The acquisition brings Celldex’s clinical-stage immuno-oncology pipeline total to seven candidates, and now includes antibodies, antibody-drug conjugates and immune system modulators. Kolltan was spun out of the Yale School of Medicine in 2007 [See Deal] and raised over $133m through four venture rounds before attempting (and ultimately withdrawing) an initial public offering in 2014. [See Deal] Investors include KLP Enterprises, Purdue, Deerfield Management, HBM Healthcare and Celtic Therapeutics Holdings.

MiRagen Goes Public Via Merger With Signal Genetics

Signal Genetics Inc. and privately held miRagen Therapeutics Inc. agreed to a merger Oct. 31 under which the stockholders of miRagen are currently estimated to become holders of approximately 96% of Signal’s outstanding common stock.

If approved by the two companies’ stockholders, the deal will create a clinical-stage, biopharmaceutical company developing proprietary micro RNA-targeted clinical product candidates addressing hematological malignancies and pathological fibrosis and pre-clinical product candidates addressing cardiovascular and neurodegenerative diseases. The total cash balance of the combined company upon the closing of the proposed merger and the financing is expected to exceed $50m. Each company’s board of directors has unanimously approved the proposed merger.

In conjunction, an investor syndicate including both existing miRagen investors and new backers committed to invest approximately $40m in miRagen immediately prior to the merger’s closing. The syndicate includes Fidelity Management and Research Company, Brace Pharma Capital, Atlas Venture, Boulder Ventures, JAFCO Co., Ltd., MP Healthcare Venture Management, Merck & Co.’s MRL Ventures, Remeditex Ventures and others.

Mylan Acquires EU Commercial Rights To Mabion’s Rituxan Biosimilar

Poland’s fledgling biotech Mabion SA has succeeded not only in securing a partnership with Mylan NV to sell its biosimilar version of Roche’s MabThera/Rituxan (rituximab) in Europe, but also is set to benefit from its partner’s regulatory expertise.

Mylan will receive exclusive rights to sell the biosimilar, Mabion CD20, in all EU countries and non-EU Balkan states, and will support Mabion in securing approval from the European Medicines Agency, the Polish company announced Nov. 8. The generics heavyweight will be involved in the long-term development of MabionCD20, and is paying an upfront fee of $10m, potential milestones of up to $35m and royalties on annual net sales to cement the deal. The biosimilar currently is being evaluated in patients with rheumatoid arthritis and lymphoma. (Also see "Tiny Mabion Races Big Pharma To EU Rituximab Market" - Scrip, 25 May, 2016.)

Mabion and Mylan are in a race with other companies to be among the first to market biosimilar rituximab in Europe, including Celltrion Inc. and Sandoz Inc., both of which already have submitted EU marketing applications for rituximab biosimilars. (Also see "Teva Plugs Gap With Celltrion Deal For Rituxan And Herceptin Biosimilar Candidates" - Scrip, 6 Oct, 2016.)

GeoVax, ViaMune Team Up To Co-Develop Immuno-Oncology Programs

GeoVax Labs Inc. and ViaMune Inc. announced an agreement Nov. 7 under which the two companies will co-develop each other’s cancer immunotherapy programs. Each company’s product candidate targets an abnormal form of the autologous cell surface-associated protein Mucin 1, which is overexpressed on most tumor types.

A tumor-associated antigen, MUC1’s overexpression often is recognized as abnormal by patients' immune system but is not sufficiently immunogenic to trigger an effective immune response that can control or eliminate tumors. The companies’ therapeutic approach will attempt to present tumor-associated antigens to the patient’s body in a different form to produce the needed immune system reaction.

The collaboration will assess each company's vaccine platform, separately and in combination, with the goal of developing a tumor MUC1 vaccine that can produce a broad spectrum of anti-tumor antibody and T-cell responses. The companies then plan to combine the resulting MUC1 vaccine with immune checkpoint inhibitors as a novel vaccination strategy for cancer patients with advanced MUC1-positive tumors.

Shanghai Henlius Gets China Rights To Abclon's Novel HER2-Targeted Therapy

Abclon Inc.'s novel HER2-targeted antibody therapy has been licensed out to China's Shanghai Henlius Biotech Inc., the Korea Drug Development Fund reported on Nov. 2. KDDF, which is a state R&D project jointly supported by three government ministries, has provided financial support to development of the therapy.

KDDF said Abclon's AC101 is an antibody drug targeting HER2 in stomach and breast cancer. It was developed using Abclon's novel epitope-screening technology (NEST) platform. Based in Seoul, South Korea, Abclon researches and develops new antibody drugs.

Under the agreement, Henlius Biotech will have the right to develop and commercialize AC101 in the China region and an option to acquire the drug's global rights. Financial terms weren't disclosed.

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

(Also see "Aimmune Gets $145m From Nestlé To Advance Food Allergy Immunotherapies" - Scrip, 4 Nov, 2016.)	Aimmune Therapeutics Inc. gained an experienced and deep-pocketed partner Nov. 4 for its experimental oral immunotherapies for food allergies as it entered into an R&D collaboration with Nestle Health Science SA, which made a $145m equity investment in the biotech.
(Also see "Medivir's Oncology Asset Purchase Seals TetraLogic's Death" - Scrip, 3 Nov, 2016.)	TetraLogic Pharmaceuticals Corp., which has been in stock freefall all year, is selling its SMAC mimetic program, including its clinical-stage asset birinapant, and its topical HDAC inhibitor, SHAPE (also known as remetinostat), to Medivir AB for $12m in cash as well as future milestones of up to $153m.
(Also see "Takeda Closing In Again On Valeant Assets?" - Scrip, 2 Nov, 2016.)	Takeda Pharmaceutical Co. Ltd. and Valeant Pharmaceuticals International Inc. are rumored to have restarted talks over some form of potential deal, this time reportedly focusing on a possible offer by the Japanese firm for Valeant's gastrointestinal business unit Salix Pharmaceuticals Ltd.
(Also see "Kolon/Mitsubishi Gene Therapy Pact Paves Way For More Global Deals?" - Scrip, 1 Nov, 2016.)	In a rare large gene therapy deal, South Korea’s Kolon Life Science Inc. is making inroads into the Japanese market through Invossa, its genetically modified allogeneic cell therapy for osteoarthritis. The agreement with Mitsubishi Tanabe Pharma Corp. could pave the way for more global licensing agreements in a growing segment.