Deal Watch: Celgene Reworks Alliance With Jounce, Gaining Global Rights To Macrophage-Targeting Candidate

Revised agreement of 2016 collaboration returns all vopratelimab rights to Jounce. Gilead fortifies antiviral pipeline in deals with Novartis, Durect.

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

Jounce Gets $50m Up Front As Celgene Largely Exits Tie-Up

Celgene Corp. continued an ongoing portfolio review ahead of finalization of its merger with Bristol-Myers Squibb Co. with an extensive reworking of its 2016 partnership with Jounce Therapeutics Inc.. Jounce will get $50m up front and potential total considerations of $530m via an unraveling that leaves it with full rights to vopratelimab (JTX-2011), the firms announced 23 July, while Celgene walks off with global rights to macrophage-targeting JTX-8064.

JTX-8064 is a selective, first-in-class antibody that may offer the potential to turn “cold” tumors “hot” – in other words, responsive to immuno-oncology therapies – by targeting the LILRB2 receptor on macrophages. The $50m to Jounce is a licensing fee – the 2016 agreement that brought the Cambridge, Mass.-based firm $225m up front plus a $36m equity investment also gave Celgene option rights to six antibodies including ‘8064 – while the biotech also can realize $480m in development, regulatory and commercial milestones, as well as sales royalties. [See Deal]

Jounce otherwise regains global rights to all antibody candidates covered under the original agreement, including vopratelimab, a binder and stimulator of ICOS (inducible T cell costimulatory) that showed improved progression-free survival and overall survival in a Phase I/II study in solid tumors reported out in April. (Also see "Jounce Gets $261m To Start, Milestone Fees Up To $2.3bn In Celgene Deal" - Scrip, 19 Jul, 2016.)

The biotech now is enrolling patients in the Phase II EMERGE study of vopratelimab in combination with ipilimumab in patients with non-small cell lung cancer or urothelial cancer who have progressed on or after PD-1/PD-L1 inhibitor therapies. It expects to report preliminary efficacy and biomarker data and biomarker data from the study in 2020.

Novartis Hands Gilead Early-Stage Antivirals

In the wake of its recently announced Galapagos NV deal, Gilead Sciences Inc. has licensed three preclinical antiviral programs from Novartis AG for an undisclosed upfront sum. (Also see "$5bn Galapagos Deal Won’t Be Last For Gilead, Says O’Day" - Scrip, 15 Jul, 2019.) The programs include investigational small molecules with therapeutic potential against human rhinovirus (the predominant cause of the common cold), influenza and herpes viruses. Their precise drug targets are also undisclosed.

The deal announced on 19 July covers global development and commercialization rights, with Novartis eligible to receive up to an additional $291m in development and commercial milestones plus royalties. Novartis announced its decision to exit the anti-infectives arena a year ago. (Also see "Alarm As Novartis Exits Antibiotics Space" - Scrip, 12 Jul, 2018.)

Following the fibrosis/inflammation mega-deal with Galapagos, this new tie-up takes Gilead closer to its beginnings in infectious disease. Gilead needs to bolster its overall pipeline to effect a long-term return to growth as sales of its hepatitis C blockbusters Sovaldi (sofosbuvir) and Harvoni (sofosbuvir/ledipasvir) burn out.

The newly licensed antivirals are still early-stage but their presence will build Gilead’s investigational antiviral portfolio, which at the clinical stage, at least, contains little outside HIV and hepatitis B. The company has a nuclease inhibitor for Ebola virus, remdesivir, in Phase II, and already markets the older flu treatment Tamiflu (oseltamivir).

Gilead Again Strengthens Antiviral R&D With Durect Deal

Days after its deal with Novartis, Gilead agreed to pay $25m up front to fellow California biotech Durect Corp. in exchange for worldwide development and commercial rights to a long-acting injectable therapy for HIV utilizing the latter firm’s SABER technology. Under an agreement announced on 22 July. Durect also could realize up to $75m in development and regulatory milestone payments, $70m in sales milestones and tiered royalties tied to the HIV candidate.

Durect says the SABER (sucrose acetate isobutyrate extended release) platform provides sustained release for injectable products, including Posimir, the company’s long-acting bupivacaine formulation for post-operative pain relief. That product is now under review by the US Food and Drug Administration after Durect responded on 27 June to a complete response letter previously issued by the agency. (Also see "Keeping Track: US FDA Closes Out First Half Of 2019 With CRL For Edsivo, But A Burst Of Supplemental Approvals" - Pink Sheet, 29 Jun, 2019.)

The deal also gives Gilead exclusive rights to employ the SABER technology in development of HIV and hepatitis B therapies, with Durect eligible for up to $150m in licensing fees, along with development, regulatory and sales-based milestones on each such product then in-licensed by Gilead. The two companies will collaborate on specified development activities, while Gilead will fund and control the work.

Neurimmune/REGENXBIO Partner On CNS Antibodies

Switzerland’s Neurimmune Holdings AG and US biotech REGENXBIO Inc. are to collaborate on delivering sustained levels of therapeutic human antibodies to the brain using AAV vectors to treat chronic neurodegenerative conditions, initially tauopathies.

Neurimmune creates human monoclonal antibodies based on those found in the healthy elderly, while REGENXBIO’s NAV viral vector technology supports the development of gene therapies. Together, the companies will be jointly responsible for the design and development of potential therapeutic antibodies and will share development costs, they announced on 24 July.

After an initial research phase, on a target-by-target basis, each company will have the option to be a co-development and co-commercialization partner or will receive a phase-based worldwide royalty. Neurimmune has been interested in neurodegenerative diseases for more than 10 years, having partnered the now discontinued Alzheimer’s disease therapy aducanumab with Biogen Inc. in 2007, and more recently inking partnerships with Ono Pharmaceutical Co. Ltd. and Eli Lilly & Co.’s Chorus unit, while REGENXBIO has more than a dozen partners and is advancing its own portfolio of gene therapy product candidates into clinical studies. (Also see "J.P. Morgan Notebook Day 4: US Generics Steady, UroGen, REGENXBIO, Dr. Reddy's In China, And Investor Sentiment Shifts" - Scrip, 10 Jan, 2019.)

Alteogen Teams With Cristalia To Develop Pediatric HGH

Alteogen Inc. said on 23 July that it has reached a co-development and license agreement with Brazil’s Cristalia Produtos Quimicos Farmaceuticos Ltda. to seek overseas clinical development of long-acting pediatric human growth hormone ALT-P1. Under the agreement, the Brazilian pharma will spend about KRW50bn ($42.4m) in progressing Phase II and III clinical trials of ALT-P1 in Brazil after manufacturing clinical samples. Alteogen will receive $2m up front; other financial details weren’t disclosed.

If clinical development is completed successfully, Cristalia will seek approval in South America, including Brazil, while Alteogen will seek to register the product in the rest of the world using Cristalia’s approval data.

The HGH market is estimated to be more than KRW4tn. Its market can be expanded to Turner’s syndrome, chronic renal failure, growth hormone deficiency in adults and prevention of aging.

Many companies progressing clinical trials of pediatric growth hormone are having difficulty recruiting pediatric patients for trials. Through the agreement, Alteogen expects to sharply reduce the clinical trial time as recruiting patients in Brazil is known to be relatively easier, Alteogen said.

ALT-P1 is a long-acting HGH using Alteogen’s NexP platform technology. Alteogen focuses on developing next-generation biobetters and biosimilars. In preclinical trials, ALT-P1 not only demonstrated greater efficacy in comparison with the first-generation HGH, but also showed longer half-life. Also, the safety of ALT-P1 was clearly proven in a Phase I clinical trial among healthy men.

A Phase IIa clinical trial for ALT-P1 is underway for adult patients with growth hormone deficiency. A Phase II trial for pediatric patients with growth hormone deficiency will soon begin in Europe, according to Alteogen’s website.

Alfasigma Licenses IBD Drug From Innovation

Weeks after it acquired irritable bowel syndrome with constipation (IBS-C) drug Zelnorm (tegaserod), recently approved by the US FDA to re-introduction into the market, from US WorldMeds LLC, Alfasigma SPA said on 23 July that it is in-licensing worldwide development and commercial rights to locally administered brilacidin from Innovation Pharmaceuticals Inc. for a pair of inflammatory bowel disease (IBD) indications. (Also see "Deal Watch: Genentech Inks New Collaborations With Skyhawk, Convelo" - Scrip, 16 Jul, 2019.)

Based in Beverly, Mass., Innovation can earn more than $24m, inclusive of an initial fee and potential milestones, plus a 6% net sales royalty on brilacidin in the agreed-upon indications of ulcerative proctitis and ulcerative proctosigmoiditis. Under the transaction, Alfasigma also gets right of first refusal for brilacidin in Crohn’s disease and ulcerative colitis, as well as right of first negotiation for the therapy in other gastrointestinal indications.

Innovation retains rights to oral formulations of brilacidin, a novel, non-corticosteroid, non-biological agent, in IBD indications as well as oral mucositis. The company already has produced successful Phase II data with the antibiotic candidate in the two indications licensed to Alfasigma. Previously, PolyMedix Inc. and successor company Cellceutix [See Deal] developed the first-in-class host defense protein (HDP) mimetic to treat acute bacterial skin and skin structure infections. (Also see "PolyMedix Progresses With Drug That Mimics Body’s Natural Protective Proteins" - Pink Sheet, 17 Oct, 2012.) Biomedtracker lists brilacidin as in Phase IIb for aBSSSI and in Phase II for ulcerative colitis and mucositis.

Ra, Camurus To Develop FluidCrystal Version Of Zilucoplan

Ra Pharmaceuticals Inc. licensed exclusive worldwide rights on 16 July to apply Camurus AB’s FluidCrystal drug delivery technology to its complement C5 inhibitor zilucoplan to treat complement-mediated diseases. Camurus gets $2m up front and can earn up to $14.5m in development milestones and other license fees, and up to $55m in sales milestones, plus tiered single-digit royalties.

FluidCrystal injection depot formulations consist of a lipid-based liquid with a dissolved active ingredient for subcutaneous administration. Once in the injected tissue, the lipid solution turns into a liquid crystalline gel to encapsulate the active ingredient for gradual release over a period of days, weeks or months.

In preclinical work conducted by the partners under a feasibility study, zilucoplan XR met all formulation, pharmacokinetic and tolerability specifications, and showed strong potential as a single-dose therapy regimen for complement-mediated diseases. Zilucoplan (in its standard form) is in Phase II trials for generalized myasthenia gravis, immune-mediated necrotizing myopathy and other tissue-based diseases. (Also see "Phase II Success Positions Ra For Potential Blockbuster Opportunity In Myasthenia Gravis" - Scrip, 10 Dec, 2018.)

Genmab Pens Bispecific Alliance With BliNK Biomedical

Genmab AS licensed exclusive rights on 16 July to use BliNK Biomedical SAS’ CD47 antibodies together with its DuoBody platform to develop new bispecific antibodies for cancer. Genmab pays $2.25m up front, with potential for $200m in development, regulatory and sales milestones, along with tiered royalties.

Genmab says the DuoBody platform provides for the discovery, generation and full-scale production of stable bispecific antibodies. The deal marks Genmab’s first step into the CD47 space for its development activities. It is already working on GEN3013 (DuoBody-CD3XCD20), targeting CD20+ B-cell malignancies including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, small lymphocytic lymphoma and marginal zone lymphoma.

Celsius Teams With Janssen In Ulcerative Colitis

Celsius Therapeutics will apply its single-cell genomics and machine learning platform to identify predictive biomarkers of response from Janssen Biotech Inc.’s VEGA study of potential combination therapy for ulcerative colitis.

Janssen will pay undisclosed upfront cash plus milestones based on the use of identified biomarkers. Celsius retains the right to integrate the clinical and sample-level data generated from the study into its database of patient and single-cell genomic information. It will use the data in future target and drug discovery activities.

The Phase IIa VEGA trial is evaluating the efficacy and safety of the golimumab/guselkumab combo therapy for ulcerative colitis. Janssen's golimumab (Simponi) is approved in the US for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis, while guselkumab (Tremfya) is approved for plaque psoriasis.

Vaxart, Janssen Vaccines Sign Agreement For Flu Vaccines

Vaxart Inc. and Janssen Vaccines & Prevention BV are partnering on a universal influenza vaccine. The collaboration announced on 9 July will assess Vaxart’s proprietary oral vaccine platform for Janssen’s influenza vaccine program. Specifically, Vaxart will produce an oral vaccine containing certain Janssen antigens. It will then be tested in preclinical studies, after which Janssen gets an exclusive option to license exclusive global rights to Vaxart’s technology.

Novartis, Mundipharma In Taiwan Ophthalmology Deal

Novartis and Mundipharma International Corp. Ltd. announced on 26 July an agreement under which Mundipharma will market, sell and distribute Novartis medicines in the general ophthalmology disease area in Taiwan. The deal includes (unspecified) medicines for glaucoma and external eye diseases and follows recent similar agreements for the Philippines and Thailand.

The partnership will allow Novartis “to focus on its existing and future portfolio in retinal disorders," said Alexis Serlin, head of the Asia Cluster for the Swiss group. Novartis will retain all international development responsibility, as well as clinical development activities for the products.

The company will also continue to manufacture and supply the medicines in its ophthalmology portfolio for commercial use.

Fujifilm Acquires Biogen Biologics Facility In Denmark

Fujifilm Corp. announced on 1 Aug. that it had completed the acquisition from Biogen Inc. of Biogen (Denmark) Manufacturing ApS, a large-scale biologics manufacturing site located in Hillerød near Copenhagen, Denmark. Fujifilm paid around $890m in cash for the facility.

With the closing of this transaction, the Hillerød facility becomes the fourth biopharmaceutical manufacturing site (after others in the US and UK) of FUJIFILM Diosynth Biotechnologies, the Japanese group’s contract development and manufacturing organization, which is a partnership with Mitsubishi Corp. Hillerød Manufacturing will change its name to FUJIFILM Diosynth Biotechnologies Denmark ApS once all regulatory procedures are complete.

The new site comprises six 15,000-liter bioreactors for the manufacture of cell culture-derived biologics for clinical and commercial use. There are around 800 employees on the campus, which also houses an assembly, labeling and packaging facility, quality control laboratories and warehouses. The Biogen products manufactured at the site will continue to be supplied under Fujifilm ownership.

Fujifilm now offers contract services across cell line and process development, manufacture and aseptic, and has the capability for biologics including recombinant proteins, monoclonal antibodies, viral vaccines and gene therapies. The company is aiming to achieve JPY100bn ($934m) in sales in its Bio CDMO business (which also includes small molecules) by the end of March 2022.

Kyongbo To Distribute Can-Fite’s Psoriasis Drug In Korea

Can-Fite BioPharma Ltd. said on 2 Aug. that it had signed a distribution agreement with Kyongbo Pharm Co. Ltd., to distribute the former’s lead drug candidate piclidenoson (CF101) for the treatment of psoriasis in South Korea, upon receipt of regulatory approvals.

Under the agreement, Kyongbo, in exchange for the exclusive distribution rights, is making a total upfront payment of $750,000 to Can-Fite, with additional payments of up to $3.25m upon achievement of certain milestones. Can-Fite will also be entitled to a transfer price for delivering finished product to Kyongbo.

Can-Fite is enrolling over 400 patients in Europe, Canada, and Israel for its Phase III Comfort trial of piclidenoson in the treatment of psoriasis. The study is designed to establish the drug’s superiority as compared to placebo and non-inferiority versus apremilast (Celgene Corp.'s Otezla) in patients with moderate-to-severe plaque psoriasis.

The global psoriasis therapeutic market, estimated to reach $11.4 bn by 2020, is dominated by biological drugs that are primarily administered via intravenous injection and have potential side effects.  dysfunction. Piclidenoson is also in Phase III trials for rheumatoid arthritis.

 

Stay tuned for the next issue of Deal Watch. You can read more about other deals that have been covered in depth by Scrip in recent days below:

(Also see "Upjohn/Mylan: Will "Potential Moderate Growth" Lure Investors?" - Scrip, 29 Jul, 2019.)	The combined company will have pro forma 2020 revenues of $19bn to $20bn, generate $1bn in synergies by 2023 and be led by [Upjohn Laboratories] CEO Michael Goettler. Mylan NV's longtime CEO Heather Bresch will depart.
(Also see "Cipla-Alvotech Prime Emerging Markets Push With Humira Biosimilar Deal" - Scrip, 29 Jul, 2019.)	Cipla Ltd. has firmed up a commercialization deal with Alvotech for the Icelandic developer’s high-concentration version of AbbVie Inc.’s Humira, continuing to use the licensing approach to expand its biosimilar franchise in emerging markets.
(Also see "Pfizer To Merge Off-Patent Business With Mylan" - Generics Bulletin, 29 Jul, 2019.)	Pfizer Inc. has announced plans to merge its off-patent unit with Mylan, creating a new generics and biosimilars giant in the US.
(Also see "Breath Therapeutics Snapped Up Post Series A By Specialty Company Zambon" - Scrip, 25 Jul, 2019.)	Italy’s privately held Zambon Co. SPA could pay up to €500m to bulk up its respiratory products pipeline, producing a nice return for Breath Therapeutics Holding BV’ syndicate of European investors.
(Also see "Newly-Formed Arrotex Is Considering Further Deals" - Generics Bulletin, 25 Jul, 2019.)	Following the formation of Australia’s Arrotex through the merger of Apotex Inc. Australia and former Strides Pharma Inc. unit Arrow Pharmaceuticals, CEO Dennis Bastas sets out the firm’s priorities as a central player in the Australian market, as well as longer-term plans to reach beyond Australia and into south-east Asia, in an exclusive interview with Generics Bulletin.
(Also see "Hikma Strikes Deal To Supply 14 To Civica Rx" - Generics Bulletin, 23 Jul, 2019.)	Hikma Pharmaceuticals PLC has struck a five-year deal with US firm Civica Rx through which it will supply 14 essential medicines to the operation aimed at tackling shortages in the US.
(Also see "UK's AMRC Licenses Shionogi Superbug Therapy " - Scrip, 22 Jul, 2019.)	As it waits for a US FDA decision on its antibiotic cefiderocol, the Japanese company has handed over the rights to a Pseudomonas aeruginosa therapy that will go into the clinic next year.
(Also see "Interview: Mallinckrodt Deal Golden For Silence Therapeutics" - Scrip, 19 Jul, 2019.)	Mallinckrodt PLC has signed a collaboration that CEO David Horn Solomon tells Scrip will help push Silence Therapeutics PLC up among its peers in the RNAi space.
(Also see "Celltrion Sets Up JV With Nan Fung To Sell Biosimilars In China" - Generics Bulletin, 19 Jul, 2019.)	Celltrion Inc. is pushing into biosimilar market opportunities in China by setting up a joint venture with local player Nan Fung Group. Vcell Healthcare is aiming to market three of Celltrion’s biosimilars as well as exploring setting up a manufacturing plant in China.
(Also see "Servier Deal Termination Fails To Dent MacroGenics’ Flotetuzumab Optimism" - Scrip, 19 Jul, 2019.)	Servier SA has handed back rights to MacroGenics Inc.’s lead DART candidate flotetuzumab. Undaunted, MacroGenics is forging ahead with clinical development including in combination use, while the market awaits a filing and license deal for its lead product margetuximab.
(Also see "Dainippon Closing In On Cell Therapy Specialist Cynata " - Scrip, 19 Jul, 2019.)	Australian venture with Phase II-ready cell therapy in sights of Sumitomo Dainippon Pharma Co. Ltd. as Japanese firm looks to build regenerative medicine interests and pipeline ahead of major expiry.
(Also see "Boehringer Further Buoys IPF Portfolio With Bridge's Autotaxin Inhibitor" - Scrip, 18 Jul, 2019.)	Pre-IPO Bridge Biotherapeutics Inc. inks major idiopathic pulmonary fibrosis license agreement with Boehringer Ingelheim GmbH, marking the biggest single product licensing out deal by a South Korean biotech. The move is poised to further bolster the German firm's leading position in the field and reflects global pharma's increasing interest in IPF.
(Also see "Interview: AbiVax Equipped To Enter Anti-Inflammatory Market " - Scrip, 17 Jul, 2019.)	Abivax’s CEO tells Scrip the firm now has the time and resources to sign up a big pharma partner for its ulcerative colitis, RA and Crohn’s candidate.
(Also see "Astellas Adds To Regenerative Medicine Portfolio In Hearing Loss Deal With Frequency" - Scrip, 17 Jul, 2019.)	Astellas Pharma Inc. adds a large-market drug candidate to its regenerative medicine portfolio, while Frequency Therapeutics Inc. almost doubles its fundraising to date. It traded ex-US rights to hearing loss candidate FX-322 for $80m up front and up to $545m in milestone fees plus royalties.
(Also see "Cipla Docks Into China, Manufacturing Plans In Tow" - Scrip, 16 Jul, 2019.)	More Indian companies are headed to China, with Cipla the latest to seal a joint venture there, though the firm has previous links with the country. Respiratory products will lead Cipla’s line-up in China, a market seen as a crucial cog in the firm’s future road map.