November 2007, Regeneron Pharmaceuticals ($REGN @Regneron) entered into a global, strategic collaboration with Sanofi ($SNY @Sanofi) to discover, develop, and commercialize fully human monoclonal antibodies (the “Antibody Collaboration”). The Antibody Collaboration is governed by the companies’ Discovery and Preclinical Development Agreement (“Antibody Discovery Agreement”) and a License and Collaboration Agreement.
Upfront Payment $85MM for Regeneron
November 2009, Regeneron and Sanofi amended these collaboration agreements to expand and extend the Antibody Collaboration. Pursuant to the Antibody Discovery Agreement, as amended, Sanofi agreed to fund up to $160.0MM per year of the Company’s research activities in 2010 through 2017.
July 2015, in connection with Regeneron’s new immunooncology collaboration with Sanofi, the Company’s Antibody Discovery Agreement and License and Collaboration Agreement with Sanofi were each amended. In connection with these amendments, Sanofi’s funding of the Company’s antibody discovery activities under the existing Antibody Collaboration was reduced to up to $145.0MM in 2015, and up to $130.0MM in both 2016 and 2017, or an aggregate reduction of $75.0MM over this threeyear period.
January 2013, Regeneron recognized as additional research and development expense $92.6 million, $109.7 million, and $17.6 million in 2015, 2014, and 2013, respectively, of antibody development expenses that Regeneron was obligated to reimburse to Sanofi related to Praluent and Sarilumab.
Profit Sharing Sanofi will lead commercialization activities for products developed under the License and Collaboration Agreement, subject to the Company’s right to copromote such products. The parties will equally share profits and losses from sales within the United States. The parties will share profits outside the United States on a sliding scale based on sales starting at 65%(Sanofi)/35% (Regeneron) and ending at 55% (Sanofi)/45% (Regeneron), and losses outside the United States at 55%(Sanofi)/45% (Regeneron).
Sales Milestone Payments Regeneron is entitled to receive up to $250MM with milestone payments commencing only if and after aggregate annual sales outside the United States exceed $1.0 billion on a rolling twelvemonth basis.
August 2008, the Company entered into a separate agreement with Sanofi, which extended through December 2012, to use Regeneron’s proprietary VelociGene® technology platform to supply Sanofi with genetically modified mammalian models of gene function and disease (the “VelociGene Agreement”). The VelociGene Agreement provided for minimum annual order quantities for the term of the agreement, for which the Company received payments totaling $21.5MM.
May 2013, the Company acquired from Sanofi full exclusive rights to two families of novel antibodies invented at Regeneron and previously included in the Company’s Antibody Collaboration with Sanofi. The Company acquired full rights to antibodies targeting the platelet derived growth factor (PDGF) family of receptors and ligands in ophthalmology and all other indications and to antibodies targeting the angiopoietin2 (Ang2) receptor and ligand in ophthalmology. As noted in the “Sanofi collaboration revenue” table above, in 2013, with respect to PDGF antibodies, Regeneron made a $10.0MM upfront payment to Sanofi, and, with respect to Ang2 antibodies in ophthalmology, the Company made a $10.0MM upfront payment to Sanofi. In addition, with respect to PDGF antibodies, the Company made two $5.0MM development milestone payments to Sanofi in 2014 and a $10.0MM development milestone payment to Sanofi in 2015, each of which was recorded as research and development expense. Regeneron is obligated to pay up to $20MM in additional potential development milestones as well as royalties on any future sales of PDGF antibodies.
July 2014, the Company purchased an FDA priority review voucher from a third party for $67.5MM. Regeneron and Sanofi equally shared the priority review voucher’s purchase price, and the Company’s share of the cost, or $33.8MM. Regeneron subsequently transferred the voucher to Sanofi, which used the priority review voucher in connection with the Biologics License Application submission to the FDA for Praluent.
May 2013 Array BioPharma (ARRY) entered into a Development and Commercialization Agreement with Oncothyreon (ONTY) to collaborate on development and commercialization of ONT380 for the treatment of cancer (previously known also as ARRY380).
Upfront Payment Oncothyreon paid Array a onetime fee of $10MM
December 2014, Array BioPharma entered into a License Agreement with Oncothyreon granting Oncothyreon an exclusive license to develop, manufacture and commercialize ONT380 an orally active, reversible and selective small molecule HER2 inhibitor.
Oncothyreon will be solely responsible for all preclinical and clinical development, regulatory and commercialization activities relating to ONT380.
Upfront Payment $20MM
> Acquirer will be required to make milestone payments of up to $280MM
> Array is entitled to receive up to a doubledigit royalty on ONT380 net sales
April 2010, Array BioPharma (ARRY) entered into a license agreement with Novartis (NVS) @Novartis which granted Novartis the exclusive worldwide right to develop and commercialize binimetinib, as well as other specified MEK inhibitors.
March 2015, Array regained these rights and the 2010 License Agreement terminated on the Effective Date of the Binimetinib Agreement.
January 2015, as amended (the “Binimetinib Agreement”), to which Array regained all development and commercialization rights to binimetinib, and by the Asset Transfer Agreement with Novartis dated January 2015 (the “Encorafenib Agreement”) to which Array obtained all development and commercialization rights to encorafenib (LGX818).
Upfront Payment $60MM, in consideration for the rights granted to Novartis under the prior License Agreement
Upfront Payment $85MM, as a result of the closing of the Binimetinib Agreement with Novartis
Array recorded the following amounts in the third quarter of fiscal 2015, resulting in a net gain on the Binimetinib and Encorafenib Agreements as follows (in thousands):
July 2013, Array BioPharma (ARRY) entered into a Drug Discovery Collaboration Agreement with Loxo Oncology (LOXO) @LoxoOncology, and granted Loxo exclusive rights to develop and commercialize certain Array invented compounds targeted at the tropomyosin kinase (“Trk”) family of receptors, including LOXO-101.
In April 2014 and again in April 2015, Array and Loxo amended the agreement to expand the research activities under the agreement. Under the terms of the amended agreement, Loxo will fund further preclinical research to be conducted by Array during the remainder of the three year discovery research phase, which may be extended by Loxo for up to two additional one year renewal periods.
Loxo will fund further discovery and preclinical research to be conducted by Array directed at other targets during the research phase of the agreement. Loxo will be responsible for all additional preclinical and clinical development and commercialization.
Array received shares of Loxo nonvoting preferred stock representing an initial 19.9% interest in the newly formed entity. Following additional financings by Loxo, Array’s ownership interest in Loxo as of June 30, 2014 was 15.3%. All of the shares of preferred stock held by Array converted into shares of common stock on the closing date of Loxo’s IPO. After certain trading restrictions ended following Loxo’s IPO, all shares were sold and as of June 30, 2015, Array has no remaining ownership interest in Loxo.
July 2013, Array BioPharma (ARRY) and Celgene Corporation (CELG) and Celgene Alpine Investment Co., LLC (collectively “Celgene”) entered into a Drug Discovery and Development Option and License Agreement to collaborate on development of an Array invented preclinical development program targeting a novel inflammation pathway.
The agreement provides Celgene an option to select multiple clinical development candidates that Celgene may further develop on an exclusive basis under the agreement. Celgene also has the option to obtain exclusive worldwide rights to commercialize one or more of the development compounds it selects upon payment of an option exercise fee to Array.
Array is responsible for funding and conducting preclinical discovery research on compounds directed at the target, and Celgene is responsible for all clinical development and commercialization of any compounds it selects.
Upfront Payment $11MM nonrefundable, received 1Q14. The majority of the upfront payment received is for the performance of research services
Milestone Payment $376MM based upon achievement of development, regulatory and sales objectives identified in the agreement, plus royalties on net sales of all drugs.
We will spend the next few sessions illuminating Array Biopharma’s (ARRY) ($ARRY) robust pipeline of clinical and pre-clinical stage partnered assets and discovery programs.
Posted in C - Clovis Oncology, C - Ethical Oncology Science, C – Advenchen Laboratories, C – Servier, License Agreements, MUT: PDGF, MUT: VEGF, SM - Lucitanib, X - Oncology, X – Cancer: Breast, X – Cancer: Lung, X – Cancer: Renal, X – Cancer: Thyroid, XX - CO, XX - France, XX - Italy, Y - 2013
November 2013, Clovis Oncology ($CLVS @ClovisOncology) acquired Ethical Oncology Science, S.p.A. (“EOS”) (known as Clovis Oncology Italy S.r.l., or “COI”) through which the rights to lucitanib were obtained.
2008, EOS had in-licensed exclusive development and commercial rights to lucitanib on a global basis, excluding China, from Advenchen Laboratories.
September 2012, EOS entered into a collaboration and license agreement with Servier, whereby EOS sublicensed to Servier exclusive rights to develop and commercialize lucitanib in all countries outside of the U.S., Japan and China.
Clovis holds exclusive rights for lucitanib in the U.S. and Japan, and is collaborating with Servier on the global clinical development of lucitanib outside of China.
Upfront Payment 1.0 Clovis $200MM to EOS, which included $190MM in $CLVS common stock (3,713,731 shares) and $10MM in cash.
Upfront Payment 2.0 In exchange for the rights granted to Servier, EOS received an upfront payment of €45.MM
Milestone 1.0 Clovis is entitled to receive additional payments on the achievement of specified development, regulatory and commercial milestones up to €100.0 MM in aggregate, of which €10.0MM was received in 1Q14
Milestone 2.0 Clovis will pay an additional $65MM to EOS upon the initial approval of lucitanib
Milestone 2.1 Clovis will also pay EOS up to an additional €115MM (~$155MM) upon certain milestones pursuant to the Servier license agreement
June 2011, Clovis Oncology ($CLVS @ClovisOncology) entered into a license agreement with Pfizer ($PFE @Pfizer) to obtain exclusive global rights to develop and commercialize rucaparib. The rights are exclusive even as to Pfizer and include the right to grant sublicenses.
Upfront Payment $7.0MM
Milestone 1 $0.4MM, April 2014, for the initiation of ARIEL3 pivotal registration study
Milestone 2.0 $88.5MM for clinical study objectives and regulatory filings, acceptances and approvals
Milestone 2.1 $20.75MM associated with the first approval of NDA (inclusive of $88.5MM value)
May 2010, $CLVS entered into an exclusive worldwide license agreement with Avila Therapeutics, Inc. (now Celgene Avilomics Research Inc., part of Celgene Corporation $CELG) to discover, develop and commercialize a covalent inhibitor of mutant forms of the EGFR gene product. As a result of the collaboration contemplated by the agreement, rociletinib was identified as the lead inhibitor candidate.
Responsible: for all nonclinical, clinical, regulatory and other activities necessary to develop and commercialize rociletinib.
Upfront payment: $2.0MM upon execution of the license agreement
Milestone 1: $4.0MM in 1Q12 upon acceptance by the FDA of IND
Milestone 2: $5.0MM in 1Q14 upon initiation of the Phase II study
Milestone 3: $12.0MM upon acceptance of NDA and MAA FDA and EMA
Let’s face it, the Technology Transfer Office (TTO) has an exceedingly difficult and complex job to do. And if not executed to perfection, while faced with so many variables beyond control of the Office, heads may easily and frequently roll.
How can we possibly improve TTO performance?
And, why should we even care to?
At its essence, the TTO mission is to jailbreak innovation in order to improve the human condition.
Clearly the Office has set a lofty aspiration bar, and why shouldn’t it? Shoot for the stars and land on the moon my madre would always say. Many of us have learned the oft-painful lesson that a worthwhile endeavor is rarely ever easy to achieve. Those of us blessed of sound mind and body and business acumen (yes all three elements are requisite) have a responsibility to serve as adjuvants (how’s that for integrating some immunology into the discourse) via this extraordinary opportunity – to make the world a better place – for those who cannot…
Historically TTO success metrics have been tethered to benchmarks such as Y/O/Y growth in numbers of invention disclosures, patents applied and issued, and licenses/options granted. Technology transfer, just as any other business, is fundamentally determined a success or failure, not so surprisingly, by focusing upon the top-line revenue performance. This is a no brainer, right? You don’t need to be a Harvard MBA to know a business can only endure for so long if operating at a loss. Well, according to a recent Brookings study, it is estimated that most universities do not generate enough licensing and royalty income to cover the wages of their TTO staff and the legal costs for the patents they file – and that over the last twenty years approximately 87% of TTOs fail to achieve break-even, staggeringly disappointing numbers indeed. Thankfully most of these offices are able to rely upon support from the broader university, as only a very small minority of TTOs are capable of self-support.
Success of the TTO has much broader and profound implications than simply a monetary return – though there are many examples of such blockbuster earnings, here are just a few in an effort to grab your attention:
It may sound pedestrian, but at its core the key to improving the human condition is via the creation of a translational culture within the hallowed halls of the research University, one that nurtures and grows innovation and where entrepreneurial thinking is fundamental – and the key performance indicator is simply … the spinout startup new company. Companies that spinout of university are disproportionately high performing, where ~8% IPO, which is ~>2X the rate of US enterprises (Litan, et. al. 2007).
We must encourage and cultivate a logarithmic acceleration in growth of the number of spinouts from the research University. As it is the spinout company that enables a nascent technology to have the best chance for achieving a commercialized product that may function to treat or cure disease, pinpoint new energy sources and stabilize existing resources, address climate change challenges, revolutionize travel, transform communication, tackle poverty, improve agricultural yields, end hunger and provide access to sufficient clean and safe drinking water to all, to name a few.
It is easy to wax poetic about what needs to be done, often less easy to illuminate how to do it. Here is my effort to suggest and willingness to work towards seeing a hastening of such an increase in spinout creation:
In an environment where the TTO is commonly under-resourced and over-burdened it is a near impossible ask for just a handful of office associates to suss data outputs from hundreds if not thousands of faculty, post-docs and graduate students and then quickly make an assessment of its downstream commercial potential. An intermediary catalyst is required to supplement the office work to identify *more* opportunity.
We should embed Entrepreneurs in Residence (EIRs) at the department level, whereby intimate relationships may be formed, beyond only faculty but to also include research associates, post-docs and graduate students.
Sidebar interesting point to note: in Norse mythology, Eir, which translates as “help” or “mercy” is a goddess associated with a medical skill.
In our example the EIR, not Eir, should be unleashed within a defined neighborhood amongst the broader University, enabling deployment of focused expertise, and one where deep understanding of potential embryonic technologies may be leveraged. Ideally the EIR should bring to bear demonstrated acumen in the departmental discipline, a history of success in the early-stage environment, an ability to manage and team build, as well as a rolodex full of public and private capital sources. These arrows in the EIR’s quiver paired with the shared passion to improve the human condition should combine to require no more than a favorable equity position in said potential spinout or spinouts as incentive-based compensation. Surely this is the characterization of a rare individual, but I know they are out there because I have met them, time and time again. The TTO does not require a line item in the budget, the EIR is focused on her mission to create a company, and the inventor receives the attention and industry-based partnership that often does not arrive in the lab until much later when precious resources may have been exhausted on purely academic experiments rather than on those that are translational in design.
Certainly as many interdisciplinary efforts are stood up, where the departmental lines are blurred – akin to for example what the University of Colorado is doing with their BioFrontiers Institute, lead by former HHMI President and Nobel Prize winner Thomas Cech, Ph.D., bringing together researchers from the life sciences, computer science and engineering to uncover new knowledge – there can easily be an EIR inserted to collaborate within the boundary lines established by such innovative units.
What we need to achieve is a Henry Ford-like mass production approach to the amplification of University spinouts. Here experts in narrowly scoped tasks staffed the continuous flow assembly line. I suggest there are similar efficiencies to be harvested via embedding Entrepreneurs In Residence at the department level, rather than by unleashing one to the entire university.
> So, if you are a potential EIR please contact me as I would be overjoyed to connect you with an interested TTO.
> And, If you are a potentially interested TTO please contact me as I would be overjoyed to connect you with a talented and eager EIR in waiting.
And finally, I would be remiss if I were to overlook highlighting Covalent Data, an Innovation Intelligence platform, specifically designed to accelerate the opportunity identification process for TTO, researcher, industry, foundation and grant agency. Yes, there is no doubt about this not-so-subtle plug, but hey, this is my blog and Covalent Data is a transformative resource that you should know about.
Comes from some other beginnings end.
Yes, this is the official final post for OnBioVC. Thank you for your readership. But, alas, I shall not go gentle into that good night. Rather, offered to you now is something more special, of greater value, contains tera-oodles of data, serves up a competitive intelligence lens like you have never before seen, and of course continues to deliver the company finance information you expect, all this and more is available to you now at Collective IP! Please observe additional details below…
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And now … dramatic fade to Semisonic.