As is customary, this month’s deals will focus on those with disclosed financial terms. April has proved to be a busy time for large pharma business development teams no doubt aiming to reinforce their “partner-of-choice” credentials during the annual BIO International Convention held in Chicago at the end of April.
See the accompanying table listing all the major pharma mergers, acquisitions and collaborations during April 2013.
Being bound to Bind– a popular choice
Bind Therapeutics did particularly well as a result of the frenzy, signing global deals with Pfizer and AstraZeneca (AZ), both based on Bind’s Medicinal Nanoengineering platform developed at Robert Langer’s MIT laboratory. This platform enables the design, engineering and manufacture of Accurins aimed at controlling drug properties, resulting in their selective accumulation in diseased tissues and cells. This maximises efficacy while minimising toxicity during treatment.
The Pfizer collaboration, involving upfront and milestone payments of up to $210m plus tiered royalties, is a preclinical research collaboration on undisclosed targets and disease focus. The deal with AZ, in oncology, follows a preclinical feasibility study on an undisclosed AZ kinase inhibitor. The companies will work together to complete IND-enabling studies. BIND will receive upfront and pre-approval milestone fees of $69m, plus $130m in payments tied to regulatory approvals and sales. Both Pfizer and AZ will retain exclusive development and commercialisation rights.
The AZ collaboration is the first firm deal to arise from several feasibility studies Bind has carried out with major pharmaceutical companies. No doubt more will soon hit the headlines.
These deals follow closely an agreement with Amgen in January again based on an undisclosed proprietary kinase inhibitor to treat a range of solid tumours. This similarly weighted deal could net Bind more than $180.5m plus tiered royalties. And if that were not enough, the biotech recently secured $20m from its venture backers to fund phase II work on its docetaxel-carrying nanotech drug BIND-014, designed to selectively target PSMA, a surface protein up-regulated in a broad range of solid tumours.
AstraZeneca down but not out….
….. and, it would seem, in it for the long haul. In addition to the Bind deal, AZ signed two further platform deals in April, neither of which are expected to deliver marketable products for years to come.
The deal with Alchemia will go some way to realising the recently announced restructuring plan in which 1,600 internal research jobs will go. AZ gains access to Alchemia’s carbohydrate chemistry expertise, proprietary diversity scanning array (DSA) library and the associated small molecule drug discovery technology VAST (Versatile Assembly on Stable Templates). The DSA contains over 14,000 unique compounds related by their 3D shape and/ or their peptidomimetic functionality. It forms the basis for the VAST platform which, when screened in high throughput screening, can identify the shape and binding elements required for target modulation. This will enable the discovery of novel small molecules against multiple AZ targets in oncology, respiratory, cardiovascular, metabolism, infection and neuroscience.
Alchemia will receive an undisclosed upfront fee, R&D expenses and up to $240m in milestones and single-digit royalties.
The third April “top 20” AZ deal is a collaboration with Horizon Discovery to explore Horizon’s first-in-class, early stage novel kinase therapy, HD-001, targeting the K-Ras mutation in various cancers including lung and colon. Importantly, K-Ras is mutated in up to 40 per cent of all cancer types causing resistance to many of the available targeted therapeutics and as a result is associated with poor patient outcomes. The development of such a molecular targeted therapy against this gene will consequently satisfy a significant unmet medical need.
Under the terms of the agreement, Horizon will receive an undisclosed upfront payment and preclinical milestones, and is eligible for clinical and approval milestones totaling up to $75m, as well as tiered royalties.
These deals, along with that announced with Moderna Therapeutics (messenger RNA therapies) and the purchase of AlphaCore (phase I programme for cardiovascular disease) earlier in the year exemplify AZ’s focus on early-stage assets and research collaborations. Will this relatively low cost bolt-on approach get the company growing again or will the time to market be time too long?
Platform technologies
Of the 11 large pharma deals announced in April, 8 involve platform technologies. In addition to those already mentioned are: Ambrx / Astellas; Isis/ Roche; Ra/ Merck; Santaris/ Bristol-Myers Squibb (BMS).
Ambrx / Astellas
The concept of antibody drug conjugates (ADCs) – pairing targeted therapeutic antibodies with potent drug payloads to treat cancer – are fast becoming irresistible to large pharma oncology teams. This passion has seemingly been ignited further by the recent FDA approvals of Kadcyla (Genentech/ ImmunoGen) and Adcetris (Seattle Genetics) both following impressive clinic trials in HER2 breast cancer and lymphoma, respectively.
As a result, companies with ADC capabilities, such as Ambrx, Mersana Therapeutics and ImmunoGen, are becoming popular partner targets for pharma companies.
Ambrx, which through its site-specific conjugation technology and proprietary linkers, claims to create higher potency ADCs with a wider therapeutic index than those created using conventional non-specific conjugation. The argument has convinced a long list of large pharma companies, including Merck & Co, BMS and Lilly, and this month Astellas (or more precisely the affiliate Agensys) has joined the club with a collaboration designed to develop and commercialise ADCs against an undisclosed number of oncology targets. Ambrx will receive $15m upfront, plus up to $285m in R&D, regulatory, and sales-based milestones. Astellas will gain worldwide rights to develop and commercialise the ADCs for oncology indications.
Isis/ Roche
Isis, another biotech with a healthy deal-making track record, including agreements with Biogen Idec and AZ, has announced a collaboration with Roche to develop treatments for Huntington’s disease. This is an inherited genetic brain disorder that results in the progressive loss of both mental and physical abilities. It is thought to affect 1 in 10,000 people in the US and the only treatment options available are symptomatic. The collaboration is based on Isis’ antisense oligonucleotide (ASO) and technology will focus initially on the lead drug candidate designed to block the production of all forms of the disease causing protein Huntingtin. Follow-up therapies that target various forms of the protein, possibly opening a path to new treatments for specific patient groups will follow. Importantly, the collaboration will also utilise Roche’s proprietary “brain shuttle” technology allowing improved blood-brain barrier penetration and facilitating systemic administration.
Under the terms of the agreement, Roche will make an upfront payment of $30m to Isis plus potential milestone payments of $362m and tiered sales royalties. Interestingly, the non-profit foundation CHDI will be reimbursed for its support of Isis’ programme. This will include a $1.5m payment upon signing the Roche agreement and additional milestones. CHDI will continue to provide advice to Isis and Roche.
Ra Pharmacuticals/ Merck & Co
Ra Pharmaceuticals entered a collaboration with Merck & Co focused on the development of Cyclomimetics, a new class of peptide-like compounds that have the diversity and specificity of antibodies while retaining the attributes of small molecules. Their novel properties enable the targeting of protein-protein interactions. Under the agreement, Ra Pharmaceuticals will use its proprietary Extreme Diversity platform to develop Cyclomimetic candidates for protein targets in multiple therapeutic areas and will be eligible to receive up to $200m in payments, including upfront and research funding, as well as discovery, development, regulatory and commercialisation milestones.
Santaris/ BMS
April also saw the announcement of yet another Santaris deal, this time with BMS to add to those already signed with Pfizer, GSK, Shire and miRagen Therapeutics. The proprietary Locked Nucleic Acid (LNA) Drug Platform is clearly another technology in high demand.
The LNA Drug Platform and Drug Discovery Engine combines the company’s proprietary LNA chemistry with its highly specialised and targeted drug development capabilities to deliver LNA-based drug candidates against previously intractable RNA targets, both mRNA and microRNA, for a range of diseases. The unique combination of this small, high affinity, potent, single-stranded LNA-based drug approach overcomes the need for complex delivery vehicles needed for earlier antisense and siRNA approaches.
Under the worldwide strategic alliance covering an undisclosed number of targets, Santaris will receive an upfront payment of $10m, up to $90m in milestone per product and will be eligible to receive royalties.
When the heat is on, old rivalries are gone
When needs must, the big players will take help from whomsoever provides it, as demonstrated by the Pfizer/ Merck diabetes worldwide (except Japan) collaboration. The partnership is to co-develop and commercialise Pfizer’s phase III ready oral sodium glucose co-transporter (SGLT2) inhibitor ertugliflozin for the treatment of type 2 diabetes, both as a standalone product and in combination with other drugs, including Januvia (Merck’s blockbuster DPP-4 inhibitor) and metformin. SGLT2 inhibitors block the reabsorption of glucose by the kidney, increasing glucose excretion, and lowering blood glucose levels.
Clearly the pressure is on, the announcement coming only a month after Johnson & Johnson obtained US approval for its SGLT2 inhibitor—Invokana (canagliflozin). In this deal, Merck gets to extend the Januvia franchise, Pfizer gets to piggyback on Merck’s diabetes franchise and part funding of the phase III trial. Pfizer has so far received $60m in upfront and milestone payments from Merck and will be eligible for additional milestone payments. Merck and Pfizer will share potential revenue and certain costs on a 60/40 percent basis.
See a table listing all the major pharma mergers, acquisitions and collaborations during April 2013