Since 2008, Exelixis and Aptuit have been engaged in a long term strategic partnership that represents a new paradigm in pharmaceutical relationships. From the beginning, Aptuit has brought to the relationship a real understanding of Exelixis' goal to redefine the way cancer drugs are discovered and developed, fundamentally changing the way cancer patients are treated. Exelixis' core strengths in biology, drug discovery and development have been built by a sense of urgency to fulfill unmet medical needs. The partnership was initiated through Exelixis' need for a strategic partner that could rapidly move multiple clinical programs forward by manufacturing, packaging and globally distributing clinical trial materials.

From the onset of the partnership, Aptuit has aided in the advance of several important molecules. Aptuit originally supported Exelixis in the manufacture of five different drug candidates that were under investigation in twelve different clinical trials. Today, Exelixis is focused on the late stage development and commercialization of cabozantinib, a small molecule. This promising molecule is designed to inhibit multiple receptor tyrosine kinases that play key roles in cellular proliferation, migration and invasion as well as angiogenesis. Exelixis is currently evaluating cabozantinib in a Phase III study for medullary thyroid cancer and in multiple Phase II studies for recurrent glioblastoma, NSCLC, SCLC, HCC, Melanoma, Breast, Ovarian, Gastric/GEJ, Pancreatic, and Prostate Cancers. The first filing is anticipated in late 2011 with an estimated approval date in early 2012. The collaborative efforts of Exelixis and Aptuit in the advancement of Exelixis' clinical pipeline was recently recognized by the 2010 Scripp Award for the Outsourcing Partnership of the Year.

Through four of Aptuit's services – solid state chemistry, drug development/manufacturing, analytical testing/validation and clinical packaging/distribution to clinical sites – Aptuit was able to provide the quality clinical services to fulfill Exelixis' initial requirements. During the past few years, as their needs have grown, Exelixis has benefited from increased support from Aptuit's roster of comprehensive services including radiochemistry, pediatric formulation development and package design and development.

The Structure of the Partnership

Today, the Exelixis/Aptuit long term strategic alliance is distinguished by a full sharing of strategy; extensive touch points throughout, built on a high level of trust that is reinforced through contracts; and the merging of the Exelixis and Aptuit cultures. Aptuit and Exelixis share a common corporate vision in their mutual goal to advance lead oncology candidates. In the initial defi ning of their partnership, Exelixis focused on its drug discovery strengths as well as certain facets of development while Aptuit provided drug development and manufacturing, analytical testing and validation, and clinical packaging and distribution to clinical sites. Today, dedicated Aptuit/Exelixis teams are working to aggressively meet timelines. They are focused on delivering the highest quality critical drugs to patients in the fastest way possible. An exceptional level of collaboration is leading to greater speed and responsiveness and a higher level of effi ciency and productivity, with Exelixis turning to Aptuit for expanded support.

The advantage of a dedicated Project Manager

The role of the Aptuit Project Manager is crucial in guiding the team to successfully complete On Time In Full (OTIF) delivery and achieve budget goals. The Project Manager takes leadership by:

• Spearheading a communications plan and full risk assessment with contingencies to mitigate obstructions in reaching milestones
• Working as the pivotal and primary liaison between Aptuit and Exelixis
• Accessing services as needed across Aptuit's multiple business lines
• Providing hands-on, real time communication and awareness of the project's critical events
• • Coordinating activities among multiple sites to ensure an uninterrupted flow
• Integrating technologies, processes and planning through Lean Six Sigma techniques and Key Performance Indicators

Mitigating risks

A significant aspect of Aptuit's contribution to the partnership is the resolution of issues as they arise, identifying manufacturing risks and uncovering the ways to mitigate them. Together, the partners have been far more effective in mitigating risks than what is experienced in traditional relationships. This success is enabled by an ongoing, honest and open dialogue that is built on mutual respect and trust. Key to the partnership's success has been the willingness of Exelixis to provide 18 months of visibility into their drug development and manufacturing plans. In turn, Aptuit has been able to thoroughly plan the manufacturing and anticipate changing needs with signifi cant lead time.

This creates built-in efficiencies, such as allowing for trouble shooting and fi nding solutions before problems occur. For example, in reviewing the Exelixis Phase III cancer program for any manufacturing risks, the team found ways to mitigate them by modifying existing equipment or securing back-up equipment. For another Exelixis cancer program, Aptuit anticipated the increasing supply requirements and identifi ed alternative manufacturing technology already inhouse. Ultimately, this technology was evaluated and implemented in advance of the clinical need. The response exceeded what is possible in a typical vendor relationship, due in large part to Aptuit's fl exible approach, diverse capabilities and the sharing of strategic objectives by Exelixis.

Access to Aptuit's solid state chemistry mitigates risk by providing:

A quantitative test for crystal forms Near-infrared imaging data to support formulation development activities, a technique that is well suited to high-throughput, quick turnaround analysis, allowing for the most recent data to be considered when making critical decisions Guidance and consulting on the interpretation of solid state property data

Aptuit's Clinical Packaging and Logistics global network

Aptuit's global reach extends to clinical manufacturing and distribution depots, which are strategically positioned to make on-site shipments to any worldwide destination, whenever and wherever needed. From January, 2008 through December 2010, Aptuit completed 83 packaging campaigns for Exelixis. As of January, 2011, Aptuit is supplying 19 protocols and shipping to sites in 30 countries.

Aptuit's CP&L team is also working with Exelixis on the design and development of the commercial packaging system.

Conclusion

Earlier in the partnership, in 2009, Aptuit was involved in work on fi ve different compounds that were related to twelve different clinical programs, spanning the course from Phase I through Phase III. Today, through development and manufacturing services, Aptuit is helping Exelixis expand their lead candidate into multiple indications and drive their fi rst commercial product to market with an anticipated approval date of early 2012.

Around the world, Aptuit's clinical manufacturing and distribution professionals, as well as other professionals across Aptuit's comprehensive business lines, are consistently able to offer their experienced insights through the strategic partnership. Aptuit's role in this partnership is distinguished by a deep, continuing commitment to help Exelixis achieve its goals. Exelixis' openness in providing Aptuit with 18 months of visibility into their development and manufacturing plans has created a climate of trust that has led to a critical differentiator – faster development and an accelerated time to market.

As the needs of their partner expand, Aptuit is positioned to provide enhanced and appropriate assistance through comprehensive services that span from discovery to commercialization. In fact, the partnership has already advanced well beyond Exelixis' original manufacturing requirements for clinical trials.

It's all about key people and the shared strengths of Exelixis and Aptuit. Today, the partners are working as a unifi ed scientifi c team, creating a new industry paradigm that sets the bar higher for strategic relationships between development stage biotechnology companies and pharmaceutical services enterprises.