Deal Watch: Alnylam/Dicerna Pact Addresses IP Questions Around Primary Hyperoxaluria Programs

The two RNAi firms cross-license IP from their PH programs, while also partnering on a rare liver disease candidate. GSK invests $250m in Vir and will help to advance its antibody candidates for COVID-19.

 

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

Alnylam And Dicerna Team Up In A1AT Deficiency-Associated Liver Disease

RNA-interference specialists Alnylam Pharmaceuticals Inc. and Dicerna Pharmaceuticals Inc. reported on 6 April that they will combine their resources to advance a candidate for alpha-1 antitrypsin (A1AT) deficiency-associated liver disease (alpha-1 liver disease), a move that analysts say should enable them to reduce crowding in that development space and compete better with rivals, including Arrowhead Pharmaceuticals Inc. and Vertex Pharmaceuticals Inc. The agreement also includes a cross-licensing of each company’s primary hyperoxaluria (PH) programs, addressing residual intellectual property disputes between the two.

The Boston-area firms agreed to have Dicerna pick up Phase I/II development of DCR-A1AT and Alnylam’s ALN-AAT02 for alpha-1 liver disease and then select the better one to advance into Phase III. Dicerna will be responsible for development costs, with Alnylam holding a right to opt in on commercialization ex-US. Cross royalty rights will apply depending on which company’s candidate advances. If Alnylam does not opt to co-commercialize, however, it will get milestones and royalties from Dicerna regardless of which drug advances.

“We believe the effort of both companies to concentrate development efforts onto one candidate is reflective of the increasingly cluttered A1AT competitive landscape and is more likely to produce an asset with a profile that will be competitive against development candidates from Arrowhead (ARO-AAT) [and] Vertex (VX814, VX864),” SVB Leerink analyst Mani Faroohar said in a 6 April note on the deal.

The cross-licensing of PH intellectual property is non-exclusive, giving Alnylam rights to Dicerna’s nedosiran for PH types 1, 2 and 3, and Dicerna rights to Alnylam’s lumasiran for PH type 1. (Also see "Dicerna Ready To Challenge Alnylam’s RNAi Dominance In 2020" - Scrip, 6 Jan, 2020.) Lumasiran has successfully completed Phase III and a rolling new drug application (NDA) is under review at the US Food and Drug Administration. A marketing authorization application for the drug was also recently submitted to the European Medicines Agency, Alnylam said on 7 April. Nedosiran (DCR-PHXC) is in Phase III development currently.

The agreement stipulates that Alnylam will pay mid- to high-single-digit royalties to Dicerna based on global net sales of lumasiran, while Dicerna will pay low-single-digit royalties to Alnylam on global net sales of nedosiran. BMO Capital Markets analyst Do Kim wrote on 6 April that the deal probably reduces clinical and commercial risk for Alnylam – as well as for both companies' A1AT programs – and gives Dicerna royalties in a later-stage PH asset, while Alnylam could benefit from financial interest in a PH drug that might serve more patients. He added that the agreement suggests some potential overlap in patent protection between the two candidates.

GSK Teams Up With Vir To Advance COVID-19 Antibody Candidates

Vir Biotechnology Inc. has been among the most visible biotechs working to address COVID-19, and on 6 April GlaxoSmithKline PLC made a $250m equity investment in the San Francisco firm as part of a collaboration in which GSK will try to accelerate antibody candidates VIR-7831 and VIR-7832 into Phase II within the next three to five months. GSK noted that both have demonstrated high affinity for the SARS-CoV-2 spike protein as well as potency in neutralizing the virus in live virus-cellular assays.

The partners also will use Vir’s proprietary monoclonal antibody technology to identify new potential therapies for COVID-19. In addition, the work will leverage GSK’s expertise in functional genomics while combining both companies’ CRISPR screening and artificial intelligence capabilities to identify candidates that target SARS-CoV-2 cellular host genes.

Other recently announced partnerships to address the pandemic include:

• Pfizer Inc. and BioNTech SE’s effort announced on 9 April to begin human testing of a vaccine by late April and produce millions of doses before the end of 2020 if they succeed. (Also see "Pfizer and BioNTech To Initiate COVID-19 Vaccine Clinical Trials In April" - Scrip, 9 Apr, 2020.)

• Cytovia Inc.’s partnership announced on 7 April with computation antibody discovery firm Macromoltek to develop dual-acting natural killer immunotherapies for the virus.

• Citius Pharmaceuticals Inc.’ six-month option to in-license a preclinical mRNA-based stem cell therapy for acute respiratory distress syndrome (ARDS) from Novellus Inc. on 1 April.

• A collaboration announced on 30 March between Aptorum Group Ltd. and Covar Pharmaceuticals to develop three repurposed preclinical drug candidates out of a screening effort of more than 2,600 candidates for COVID-19.

• Samsung BioLogics inked a binding agreement on 12 April with Vir to manufacture a coronavirus-neutralizing antibody (SARS-Cov-2 mAb DS) for clinical trials and commercialization, according to a stock market disclosure in South Korea. The deal is worth about $362m.

Zai Licenses China-Plus Rights To Regeneron’s Bispecific Antibody

Regeneron Pharmaceuticals Inc. on 8 April announced a collaboration for the development and commercialization by China’s Zai Lab Ltd. of the bispecific antibody REGN1979 in oncology in mainland China, Hong Kong, Taiwan and Macau. The deal will also support enrollment in the global clinical trials of REGN1979, starting with the ongoing and potentially registrational Phase II program in B-cell non-Hodgkin lymphoma (NHL).

REGN1979 is the most advanced investigational bispecific monoclonal antibody from Regeneron's bispecific platform (which enables no linkers or artificial sequences) and is designed to trigger tumor killing by linking and activating a cytotoxic T-cell (binding to CD3) to a lymphoma cell (binding to CD20). (Also see "Regeneron Wades Deeper Into Oncology With Ambitions To Be A Force In The Space " - Scrip, 6 Feb, 2020.)

Regeneron will receive $30m up front and is eligible for up to $160m in additional regulatory and sales milestones. Zai Lab will contribute to the global development costs for REGN1979 for certain trials and will make payments to Regeneron based on net sales, such that the US firm shares in a “significant portion” of any potential profits. Regeneron will be responsible for the manufacture and supply of REGN1979.

Non-Hodgkin lymphomas have annual incidence and death rates in China of more than 88,000 and 48,000, respectively, as of 2018. B-cell NHL accounts for 85% of all NHL cases. REGN1979 already has orphan status in the US for follicular lymphoma and diffuse large B-cell lymphoma and is being investigated in these and other lymphomas.

Janssen, ImmunoPrecise Partner On Antibody Research

Janssen Pharmaceutical Cos. announced a research agreement on 14 April with contract research organization ImmunoPrecise Antibodies Ltd. giving Janssen access to a panel of novel monoclonal antibodies against an undisclosed target. The pharma also got an option to acquire all commercial rights to the antibodies. No financial terms were disclosed.

Kite Licenses Multiple Myeloma Candidates From TeneoBio

Gilead Sciences Inc.’s cancer cell therapy subsidiary Kite Pharma Inc. said on 2 April that it had licensed B-cell maturation antigen (BCMA) antibody candidates for multiple myeloma from TeneoBio Inc. Derived from the latter’s Human Heavy-Chain Antibodies (UNIMab) platform technology, the Phase I candidates bring next-generation dual-targeting chimeric antigen receptor T-cell (CAR-T) to Kite's existing pipeline. No financial terms were revealed.

Myovant Licenses Ex-US Relugolix Rights To Gedeon Richter

Budapest-based Gedeon Richter PLC agreed to pay $40m up front on 31 March to obtain ex-US commercialization rights to Myovant Sciences Ltd.’s relugolix combination (relugolix 40mg/estradiol 1mg/norethindrone acetate 0.5mg) medication for uterine fibroids and endometriosis. Myovant retains US rights to the products as well as all global rights to the combination pill in non-women’s health indications.

In addition to the upfront payment, Myovant can realize up to $147.5m in regulatory and sales milestone payments under the deal as well as tiered royalties on sales in Gedeon Richter’s territories, which include Europe, Russia, the Commonwealth of Independent States, Latin America, Australia and New Zealand.

Servier Agrees To Acquire Symphogen

With the two companies already partnered since 2018 on an immuno-oncology R&D effort, Servier SA said on 3 April that it had agreed to acquire 100% of Danish antibody discovery biotech Symphogen AS at undisclosed terms. The French firm said the acquisition will add to its antibody pipeline and bring it next-generation antibody technology.

Horizon Pays $45m For Curzion, Rare Rheumatic Disease Candidate

Horizon Therapeutics PLC agreed on 2 April to pay $45m with potential for contingent development and regulatory milestones for privately held Curzion Pharmaceuticals Inc., in the process acquiring its Phase II candidate for diffuse systemic cutaneous sclerosis, an unmet medical need. CZN-001, to be renamed HZN-825, is an oral, selective lysophosphatidic acid 1 receptor (LPAR1) antagonist originally discovered by Sanofi. With a successful short-term Phase IIa study complete, Horizon said it will work with the FDA to design a potentially pivotal Phase IIb study of the asset to begin in the first half of 2021.

Shenogen Acquires Chinese Rights To BioArdis’ HCC Candidate

On 3 April, Chinese firm Shenogen announced an exclusive collaboration and licensing agreement with Shanghai BioArdis Co., Ltd. and BioArdis LLC for the development and commercialization of BioArdis' novel FGFR4 (fibroblast growth factor receptor 4) kinase inhibitor, BIO-1262/SNG-203, either as monotherapy or combination therapy, in mainland China, Hong Kong, Macau and Taiwan. BioArdis will retain all rights in the rest of the world and Shenogen will be responsible for all development and commercialization activities in its territories.

BIO-1262 is being evaluated as a potential new treatment for hepatocellular carcinoma (HCC) and other solid tumors positive for FGFR4 and KLB (klotho beta) expression. Fibroblast growth factor receptors (FGFRs) play a key role in regulating cell survival and proliferation and a growing body of evidence suggests they also play a role in cancer progression.

Shenogen’s icaritin is currently in late Phase III trials for the treatment of advanced HCC as a single agent and in combination therapies, and the Beijing-based company sees BIO-1262/SNG-203 as potentially best in the FGFR4 class and as solidifying its portfolio in the indication. Financial terms of the new deal were not disclosed.

Samsung BioLogics Inks Development, Manufacturing Partnership With PharmAbcine

Samsung BioLogics has reached a strategic partnership with PharmAbcine Inc. for the development and manufacturing of PMC-402, a next generation therapeutic antibody candidate to treat oncology and neovascular disorders. Under this agreement, Samsung will provide the full scope of its CDO services from cell line development, process development, cGMP clinical manufacturing to investigational new drug (IND) application filing support, Samsung said 5 April.

PharmAbcine is a clinical-stage biotech company developing fully human therapeutic antibodies to treat cancer and neovascular disease. Olinvacimab, the company's lead molecule, is in Phase II clinical trials for combination use with Merck & Co. Inc.'s Keytruda (pembrolizumab) to treat cancer.

According to PharmAbcine, PMC-402 is expected to enhance the delivery of immune cells and cancer therapeutics to treat tumor cells via active normalization of leaky blood vessels. Attributable to its vessel-normalization characteristics, PharmAbcine plans to expand the indication to eye diseases such as wet age-related macular degeneration and diabetic retinopathy.

Stay tuned for the next edition 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 "Coronavirus Update: Sanofi And GSK Unveil 'Unprecedented' Vaccine Alliance" - Scrip, 14 Apr, 2020.)	Plus: Eli Lilly & Co. unveils Olumiant COVID-19 study, Samsung and Vir to collaborate on antibody, Korean industry asks for government assistance.
(Also see "Kyowa Kirin Goes Global With MEI’s PI3K Contender In $683m Deal" - Scrip, 14 Apr, 2020.)	Japanese firm builds on existing alliance to gain most global rights to US company’s potential best-in-class drug for lymphoma and B-cell malignancies.
(Also see "CSL Behring And SAB Explore Polyclonal Antibodies For COVID-19" - Scrip, 9 Apr, 2020.)	CSL Behring is backing the US biotech SAB Biotherapeutics Inc. in developing polyclonal antibodies in cattle for their efficacy against the pandemic virus, adding a second strand to the research efforts of the blood products specialty company.
(Also see "Circassia Ends AZ Deal To Dig Itself Out Of Debt Hole" - Scrip, 9 Apr, 2020.)	Circassia Pharmaceuticals PLC is returning the US rights to two COPD drugs to AstraZeneca PLC as it admits it cannot meet its debt payments from the deal.
(Also see "Henlius Partners With Mabxience On Trastuzumab" - Generics Bulletin, 9 Apr, 2020.)	Shanghai Henlius Biotech Inc. has struck a deal with Mabxience to market its HLX02 trastuzumab biosimilar in Argentina, Uruguay and Paraguay.
(Also see "Arrakis Inks First Partnership In RNA-Targeted Collaboration With Roche" - Scrip, 8 Apr, 2020.)	Biotech gets $190m up front in partnership that will discover small molecule RNA-targeted therapies against a range of targets selected by Roche. Arrakis Therapeutics Inc. thinks its technology can drug difficult-to-reach targets.
(Also see "Takeda, CSL, Other Blood Plasma Firms Team On Hyperimmune COVID-19 Therapy" - Scrip, 6 Apr, 2020.)	Deal Snapshot: Six companies seek to collect convalescent plasma from COVID-19 survivors to quickly develop hyperimmune immunoglobulin therapy for serious complications of the virus.
(Also see "Gilead Moves Into Microbiome In Deal With Second Genome" - Scrip, 6 Apr, 2020.)	Gilead lands on Second Genome Inc. as its first partner to apply microbiome analysis to pipeline assets to look for biomarkers. Companies also team up on GI drug discovery.
(Also see "Evotec Extends Takeda Pact to Gene Therapy" - Scrip, 6 Apr, 2020.)	Evotec SE is building a gene therapy R&D center manned by ex-Takeda Pharmaceutical Co. Ltd. scientists and has already landed a multi-year drug discovery pact for it with their former Japanese employer.
(Also see "Akorn Defaults On Loan Agreement After Sale Bid Falls Flat" - Generics Bulletin, 6 Apr, 2020.)	Facing soaring legal costs stemming from its failed merger with Fresenius Kabi AG and burdened by substantial debt, Akorn Inc. elected to put itself up for sale earlier this year in order to help repay lenders. But the company has now defaulted on an agreement with its creditors after no bidder stepped up to the plate.
(Also see "Amid Aborted Sandoz Deal, A Silver Lining For Aurobindo?" - Scrip, 5 Apr, 2020.)	The termination of the Aurobindo Pharma Ltd.-Sandoz International GMBH deal isn’t perhaps all bad news for the Indian firm and the flip side may be an improved balance sheet, according to some analysts. But the resolution of compliance issues at manufacturing facilities remains critical.
(Also see "J&J Spots Potential Of Fate’s Stem Cells, Signs Cancer Deal Worth Up To $3bn" - Scrip, 3 Apr, 2020.)	Investment from Janssen helps to validate the platform developed by the San Diego-based company.
(Also see "Neuraxpharm Allies With Panaxia On Cannabis Portfolio" - Generics Bulletin, 2 Apr, 2020.)	CNS specialist neuraxpharm Arzneimittel GmbH has struck a deal with Israel’s Panaxia to market medical cannabis products in Europe, starting in Germany.
(Also see "Aurobindo-Sandoz End $1bn US Deal" - Scrip, 2 Apr, 2020.)	Aurobindo and Sandoz mutually terminate their planned $1bn deal, leaving many questions on how both sides will re-orient strategies going forward.
(Also see "Manipulating Metabolism: Lilly Links With UK Biotech Sitryx" - Scrip, 31 Mar, 2020.)	Duo will study up to four novel preclinical targets identified by Sitryx Therapeutics that may lead to potential new drugs for autoimmune diseases, which Lilly would then commercialize.
(Also see "Mylan Bids To Win EU Approval For Upjohn Merger" - Generics Bulletin, 31 Mar, 2020.)	Mylan NV and Pfizer’s [Upjohn Laboratories], already facing a delay to their proposed merger, may have to overcome regulatory barriers to get the deal over the line.