Life sciences licensing deals in the fourth quarter of 2017: updates and trends

During the fourth quarter of 2017, Cortellis Competitive Intelligence registered 1,107 new deals (excluding mergers & acquisitions) as part of its ongoing coverage of licensing activity in the life sciences sector compared to 1,043 in the third quarter and 1,035 in the fourth quarter of 2016.


High-value deals: worth $0.5 billion or more

We tracked 49 high-value new partnerships, worth in excess of $100 million, during the fourth quarter of 2017. The following is a selection of deals valued at more than $0.5 billion, which were predominantly milestone-based (Figure 1).


Eli Lilly exchanges $1.8B to use CureVac’s RNActive platform for five cancer vaccines

Eli Lilly teamed up with CureVac to generate up to five cancer vaccines containing neoantigen-encoding mRNA delivered using CureVac’s RNActive technology which elicits an immune response against the encoded neoantigens. CureVac nets an upfront of $50 million, upfront equity of $53 million and more than $1.7 billion in milestones plus royalties.


Bayer takes on Loxo’s tropomyosin receptor targeting anticancer agents for $1.5B

Loxo Oncology’s tropomyosin receptor kinase-specific anticancer programs caught Bayer’s attention for an upfront $400 million, $1.150 billion in milestones plus royalties. LOXO-101 (larotrectinib) is awaiting US approval, while LOXO-195 is in phase II with recent positive clinical data. Bayer obtained worldwide rights except for in the U.S.


Boehringer Ingelheim dispenses with $674M for Autifony’s potassium channel modulator against CNS disorders

Boehringer Ingelheim gained an option to advance Autifony’s potassium channel modulator AUT-00206 for CNS disorders. The phase I candidate had shown good progress in schizophrenia and will set BI back $29 million upfront, up to $645 million in milestones plus royalties.


Roivant pledges $502M for HanAll’s anti-Fc neonatal receptor mAb for autoimmunity

Rights to develop HanAll’s HL-161, an anti-Fc neonatal receptor mAb targeting autoimmune diseases, in the Americas, Europe, the Middle East and North Africa have been given to Roivant. The phase I agent attracted $30 million upfront, $20 million in research funding, milestones of $452.5 million, plus royalties.


Janssen dispenses with $1.4B to access Zymework’s antibody platforms

Janssen gained access to Zymeworks’ Azymetric and EFECT platforms to develop up to six bispecific antibodies against undisclosed indications for an upfront $50 million, up to $282 million in development and up to $1.4 billion plus royalties. Janssen also had the option for two additional bispecific antibodies.


AskAt’s anticancer EP4 receptor antagonists is subject of Arrys’s $1.2B pledge

Arrys would take AskAt’s AAT-007 and AAT-008, prostaglandin EP4 receptor antagonists, worldwide excluding China to treat cancer. The early-stage candidates target EP4 in order to stimulate the immune system in tumors by enabling natural killer and cytotoxic T-cells to attack cancer cells. Arrys would depart with more than $1.2 billion in upfront and milestone payments plus royalties.


PetiDream’s peptide platform is the heart of $1.1B cardio/cancer license option with Bayer

Bayer and PeptiDream would use PeptiDream’s Peptide Discovery Platform System to identify macrocyclic/constrained peptides to target cardiovascular diseases and cancer in a partnership worth $1.11 billion in milestones plus royalties. Bayer could opt to extend the use of the platform in the areas of peptide-drug conjugates, diagnostics, bioimaging and agriculture.


$1B alliance forms between Alnylam and Vir to silence hepatitis B virus with siRNA

Alnylam and Vir would advance ALN-HBV-02, a small interfering RNA designed to silence expression of the hepatitis B virus gene. It has increased potency and durability, and a wide therapeutic index compared to conventional siRNAs through the binding with GalNAc (N-Acetylgalactosamine), an amino sugar derivative of galactose using Alnylam’s enhanced stabilization chemistry-plus (ESC+) GalNAc conjugate technology. Alnylam would receive an upfront payment, more than $1 billion in potential milestones plus royalties.


Visterra’s Hierotope platform generated anti-infectious antibodies lures Vir for $1B

Visterra and Vir will be using the former’s computational Hierotope platform to design and engineer antibodies, which bind to epitopes found within antigens, to target infectious diseases. Vir gained access to a number of candidates including VIS-FLX, a long-acting mAb (mAb) for influenza A; VIS-RSV, a bispecific mAb for respiratory syncytial virus (RSV); VIS-FNG, a bispecific mAb for severe fungal infections including Candida, Aspergillus and Cryptococcus; up to two additional infectious disease research programs and an option to a minority financial interest in VIS-410, a mAb for hospitalized patients with influenza A. Visterra stands to gain more than $1 billion in milestones, royalties.


MacroGenics attracts $0.9B from Incyte for cancer agent MGA-012

MacroGenics parted with MGA-012 as Incyte looked to progress the anti- programmed cell death protein 1 mAb in phase I studies for solid tumors and hematological malignancies. Incyte will release an upfront $150 million, up to $750 million in milestones plus royalties.


Multiple sclerosis candidate PRN-2246 is central to Principia and Sanofi’s $0.8B license

Principia’s bruton’s tyrosine kinase inhibitor, PRN-2246, drew up interest from Sanofi as the former looked to move the program past healthy volunteer testing and towards multiple sclerosis patients. Principia would receive $40 million upfront, milestones of $765 million plus royalties. Principia’s pipeline is based on its tailored covalency technology whereby a strong, long-lasting but reversible interaction is formed between the drug and the target, thereby improving drug efficacy and reducing drug exposure.


Merck & Co. monitors KalVista’s KVD-001 for diabetic macular edema before committing $0.75B

Merck & Co. is watching a phase II proof-of-concept trial of KalVista’s KVD-001, an intravitreal formulation of plasma kallikren inhibitor, very closely before it decides to commit to acquiring the diabetic macular edema treatment. The option would cost Merck $37 million upfront, up to $715 million in options and milestones, plus royalties. At the same time, Merck acquired 9.9% of KalVista for $9.1 million.


Alexion doses ravulizumab for blood disorders using Halozyme’s ENHANZE delivery platform for $0.68B

Alexion intends to use Halozyme’s ENHANZE technology to deliver subcutaneous formulations, for up to four targets, including ravulizumab (ALXN-1210), a humanized mAb that blocks complement C5 activity in phase III for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. The ENHANZE technology consists of a recombinant human hyaluronidase enzyme (rHuPH20) that temporarily degrades hyaluronic acid in tissue to aid in the dispersion and absorption of subcutaneously injected drugs. Halozyme is projected to receive $40 million upfront, up to $160 million in milestones per target plus royalties.


Depomed nets $0.55B with Collegium marketing Nucynta in the U.S. for pain

After purchasing U.S. rights to tapentadol (Nucynta) from Janssen and relaunching it, Depomed sublicensed marketing rights to Collegium for the pain treatment. The norepinephrine reuptake inhibitor and muscurinic opioid receptor agonist comes in both immediate- and sustained-release formulations and could be used with Collegium’s opioid abuse deterrent, oxycodone (Xtampza). Depomed would earn $10 million upfront plus royalties.


Boehringer releases melanoma agent BI-882370 to Xynomic for $0.5B

Despite recently showing superiority over widely available metastatic melanoma treatment vemurafenib (Zelboraf), dabrafenib (Tafinlar) and trametinib (Mekinist), Boehringer Ingelheim released BI-882370 to Xynomic. The discovery stage, RAF inhibitor would cost $502 million in upfront and milestone payments plus royalties.


Prolific deal makers

The most prominent deal figures over the fourth quarter were the usual big biopharmaceuticals including Boehringer Ingelheim, Roche and Takeda.


Boehringer Ingelheim

iPharma planned to conduct phase I/II studies for BI-853520 with immune checkpoint inhibitors against cancer in exchange for undisclosed upfront, milestone and royalty payments (Figure 2).  The focal adhesion kinase 2 inhibitor had been tested in the clinical setting for pancreatic adenocarcinoma, platinum-resistant ovarian cancer, esophageal cancer and soft tissue sarcoma.

MiNA Therapeutics’ small activating RNA (saRNA) platform was targeted to generate treatments for up to three targets surrounding fibrotic liver diseases, including non-alcoholic steatohepatitis (NASH). These saRNAs facilitate expression of mRNA, which then upregulate therapeutic proteins, consequently restoring metabolic functionality of hepatocytes and preventing fibrotic tissue formation. MiNA would net upfront, funding and milestone payments of around $355 million plus royalties.

CellSight Technology welcomed involvement to assess the capability of its radiolabeled, guanosine analog imaging agent VisaAcT in predicting immunological response to PD-1 checkpoint inhibition in squamous cell carcinoma of the head and neck. The tracer is taken up by activated T cells, enabling the non-invasive determination of changes in T cell activation within tumor lesions. It was already being tested with Genentech’s atezolizumab (Tecentriq) in bladder cancer and was due to be evaluated in graft versus host disease.

Figure 2: Selection of Boehringer Ingelheim deals in Q4 of 2017. (Source: Cortellis Competitive Intelligence, Clarivate Analytics)


Dicerna’s GalXC technology would be used to develop an RNAi agent to inhibit the expression of and silence genes associated with chronic liver diseases, including NASH with an option for a second target. A $10 million upfront payment would be made with up to $191 million in milestones plus royalties.

Roche would use its locked nucleic acid (LNA) technology to produce LNA oligonucleotides that inhibit RNA targets in inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis. Roche acquired the technology from Santaris in August 2014.



Idorsia is giving an exclusive option to an immune-oncology program, which will developed under a joint committee led by Idorsia, in return for $52 million upfront, around $425 million in milestones plus royalties. The announcement comes not long after Janssen exercised an option to partner with the Actelion spin-off on its phase II essential hypertension therapy, aprocitentan, for $235 million in milestones and up to 35% in royalties.

Confo, a Flanders Interuniversity Institute for Biotechnology spin-off, attracted attention towards its G-protein coupled receptor (GPCR) agonists targeting neurological and developmental disorders. The program consists of confobodies, camel single domain antibodies, which stabilize distinct druggable conformers of GPCRs to ensure only the correct cellular pathway is altered. It would provide Confo with upfront, funding and milestone payments totaling just over $100 million.

Warp Drive Bio’s genome mining platform will be used to identify synthetic antibiotics, based on their genomic profiles, against drug-resistant, Gram-negative pathogens. Warp Drive would gain up to $87 million in upfront payment, option fees, preclinical milestones and up to $300 million in non-preclinical milestones plus royalties.



HemoShear’s REVEAL-Tx platform is being used to create candidates for liver diseases including NASH. The platform replicates a disease environment by applying principles of physiological blood flow to tissue from patients, allowing for the study of drug candidates against complex pathophysiological pathways at human concentrations. Use of the platform would incur undisclosed upfront payments and funding, $470 million in milestones plus royalties.

Portal Instruments’s needle-free drug delivery device will be used to deliver the alpha-4/beta-7 integrin receptor antagonist, vedolizumab (Entyvio), in phase III trials against ulcerative colitis and Crohn’s disease. The biologic is delivered through a pressurized liquid instead of a needle with less pain. Portal would net an undisclosed initial payment, milestones of up to $100 million plus royalties.

Recursion would use its phenotypic screening platform, which applies advanced imaging, artificial intelligence and machine learning tools to low-tech cellular disease models, to identify candidates for rare diseases. Recursion would earn an undisclosed upfront payment, more than $90 million in milestones, plus royalties.



Recipients of the largest milestone payments during the quarter included AiCuris, Enanta and Genmab, PTC Therapeutics and Impact (Table 1).

Merck & Co sent $122 million to AiCuris following the U.S. approval of letermovir (Prevymis) for cytomegalovirus infection. Merck took over development in October 2012 for the quinazoline-based terminase inhibitors for $574 million.

Enanta received a total of $65 million following U.S. and E.U. approval of Maviret to target hepatitis C virus (HCV) as well as $15 million triggered by Japanese reimbursement approval. The partnership for the fixed-dose combination of glecaprevir and pibrentasvir, which had since been launched, was established in November 2006 for $307 million.

Table 1: Top milestone payments in Q4 of 2017. (Source: Cortellis Competitive Intelligence, Clarivate Analytics)


With the first sale of daratumumab (Darzalex), a CD38 molecule targeting antibody targeting multiple myeloma, in Japan, Janssen rewarded Genmab $25 million. This was followed by $50 million as sales volumes reached $1 billion for the same disease. The submission of an application to the European Medicines Agency to expand an existing marketing authorization then facilitated $3 million. Finally, clinical success displayed in a phase III ANDROMEDA (AMY-3001) trial with cyclophosphamide, bortezomib and dexamethasone resulted in a further $20 million to Genmab.

Roche initiated part II of a study (SUNFISH) assessing efficacy and safety of survival motor neuron (SMN)2 gene splicing modulator RG-7916 in spinal muscular atrophy 24 months after dosing, triggering $20 million to PTC Therapeutics. The alliance was formed in November 2011 for $490 million.

After the FDA lifted a hold on a phase II trial involving suspected cases of Wernicke’s encephalopathy in patients receiving fedratinib for myelofibrosis, Impact received $20 million from Oberland Capital. The $90 million milestone-based funding was pledged in October 2017.


Options and terminations

During the quarter, there were some options exercised and a high number of terminations.

Eisai opted for co-responsibility over Biogen’s beta-amyloid targeting mAb aducanumab against Alzheimer’s disease (AD). Profits would be split by territory for the phase III candidate. The collaboration, which included a number of AD treatments, began in March 2014 for $1.1 billion.

Ionis received a $5 million license payment from Janssen, presumably relating to an exercised option to the second recently disclosed, orally delivered Generation 2.5 antisense oligonucleotide, IONIS-JBI2-2.5Rx, targeting a gastrointestinal (GI) autoimmune disease. The partnership for RNA-targeted antisense candidates against GI autoimmune diseases was established in January 2015 for $835 million.

Another of Ionis’s assets, IONIS-HTTRx, was snapped up by Roche following the completion of a phase I/II trial. The antisense oligonucleotide, huntingtin protein blocker which treats Huntington’s disease, netted Ionis a license fee of $45 million from a pre-agreed total of $392 million in April 2013.

After receiving notice from Alexion in July 2017 wishing to end its involvement in BLU-782 for fibrodysplasia ossificans progressive following a strategic portfolio review as part of its corporate restructure, Blueprint regained rights to its activin receptor type-1 inhibitor. Alexion took on the activin receptor type-1 inhibitor in March 2015 for $265 million.

As BTG breached its distribution contract with Wellstat for uridine replacement agent Vistogard for 5-fluorouracil/capecitabine chemotherapy related toxicity for undisclosed reasons. Wellstat expected $55.8 million in damages plus interest and costs. BTG gained rights in July 2011 to market the drug in the U.S. in exchange for an upfront $7.5 million.

Achillion regained its HCV assets after Janssen cited a competitive HCV market followed by a strategic decision to discontinue the development of JNJ-4178 (triple combination of simepravir/odalasvir/adafosbuvir). Achillion handed over various HCV candidates to Janssen in May 2015 for $1.1 billion.

Chiesi Farmaceutici pulled out from distributing Kamada’s alpha-1 proteinase inhibitor for alpha-1 antitrypsin deficiency in Europe after Kamada’s recent withdrawal of a marketing authorization application. The EMA did not view the filed data sufficient for MAA approval, requesting an additional clinical trial to assess long-term efficacy and safety. Chiesi was to expect $60 million in milestones for the 12-year exclusive distribution deal, which began in August 2012.

SymBio returned pain treatment Ionsys to the The Medicines Company (TMC) and was seeking damages of $82 million for breach of contract. SymBio claimed that TMC failed to provide adequate assurances of performance of its obligations by withdrawing the needle-free transdermal formulation of fentanyl. The reason for withdrawal was unclear, however, TMC expected to make an annual $35 million in cost savings associated with the termination of the drug and a staff reduction. SymBio agreed in October 2015 to exclusively develop and market the treatment in Japan in exchange for $10 million upfront plus milestones and royalties.

Otsuka ended its involvement for GW Pharmaceuticals’s Sativex, a tetrahydrocannabinol buccal spray treating cancer pain, in exchange for regulatory and sales milestones. The spray was beset with negative data from pooled phase III trials as it failed to significantly reduce pain compared to placebo. Otsuka planned in February 2007 to progress the spray in the U.S. for cancer pain for $291 million.

Outlook for the first quarter of 2018

At the beginning of the first quarter of 2018, deal reports continue to be added to Cortellis Competitive Intelligence. In the first few days of January, early projections highlighted that Incyte gained an exclusive option to Syros’s discovery stage myeloproliferative neoplasm program based on Syros’s gene control platform, which identifies disease-causing alterations in gene expression. Incyte would part with $10 million upfront, $10 million in stock, up to $54 million in target selection milestone payments and option exercise fees and, for up to seven targets, $805 million in milestones plus royalties. Takeda would collaborate with Denali on three neurodegenerative disorder candidates based on Denali’s Antibody Transport Vehicle platform. Takeda would have an option for full rights for an upfront $40 million, $110 million in upfront equity, $15 million in option fees, just over $1 billion in milestones, plus royalties.



Clarivate Analytics is pleased to announce the return of our esteemed Cortellis Deals of the Year. Partnerships are the lifeblood of the biopharma industry. But what makes a good deal? Our experts at Cortellis have sifted through the licensing partnerships and mergers & acquisitions of 2017 and have nominated five deals in each category for the Clarivate Analytics Cortellis Deals of the Year. Review the deals and vote now!