About Pfenex

Pfenex Inc. operates as a development and licensing biotechnology company. The company focuses on leveraging its proprietary protein production platform, Pfenex Expression Technology, to develop next generation and novel protein therapeutics to meaningfully improve existing therapies and create novel therapies for some of the biological targets linked to critical diseases still waiting to successfully be addressed. The company has experience in protein therapeutic development and its proven platform enables deliberate and rapid candidate selection, fast drug development, and higher success rates for a range of complex modalities. The company intends to leverage existing drug development successes into a pipeline that is diversified across multiple assets, including the U.S. Food and Drug Administration (FDA) approved, next generation and novel biopharmaceutical products. In October 2019, the FDA approved the new drug application (NDA) for PF708 under the 505(b)(2) regulatory pathway, with Forteo (teriparatide injection) as the reference drug. The FDA-approved PF708 product is indicated for the treatment of osteoporosis in certain patients at high risk for fracture. Marketing authorization applications (MAAs) are pending in other jurisdictions. This FDA-approved PF708 product would be commercialized and manufactured in the U.S. by the company’s collaboration partner, Alvogen Malta Operations Ltd. (Alvogen). In November of 2019, in accordance with the development and license agreement, the company transferred the NDA to Alvogen. Alvogen intends to launch the FDA-approved PF708 product in the U.S. upon an FDA decision on the therapeutic equivalence evaluation of the product. The company’s other products and collaborations include PF743 (JZP-458), which it is developing in collaboration with Jazz Pharmaceuticals Ireland Limited (Jazz) for the treatment of acute lymphoblastic leukemia (ALL) and which commenced a pivotal Phase 2/3 clinical study in December 2019. The company also has collaborations based on CRM197, a diphtheria toxoid carrier protein used in prophylactic and therapeutic vaccine candidates with Merck & Co., Inc. (Merck) and Serum Institute of India Private Limited (SIIPL). Both Merck and SIIPL have licenses to the Pfenex Expression Technology for the production of CRM197 for use in conjugate vaccine products. Merck’s V114, a 15-valent Pneumococcal conjugate vaccine is in 15 Phase 3 clinical trials, and SIIPL’s Pneumosil, a 10-valent Pneumococcal vaccine designed for the developing world, achieved World Health Organization (WHO) Prequalification allowing the product to be procured by United Nations agencies and Gavi, the Vaccine Alliance. In addition, a Phase 3, randomized, double-blind study to evaluate the immunogenicity, safety and tolerability of Pneumosil in healthy Indian infants has been completed and SIIPL is in the process of submitting the data from the Phase 3 trial to the Drug Controller General of India in the support of India marketing authorization. In 2019, the company added PF810, a peptide based next generation therapeutic, to its wholly owned pipeline. PF810 is in preclinical development. In addition, the company has established a strategic collaboration with Arcellx, Inc. (Arcellx) to advance multiple proprietary sparX proteins that activate, silence, and reprogram Antigen-Receptor Complex T cell based therapies based on the Arcellx product platform. FDA-Approved Product, Product Candidates and Collaborations The company’s pipeline includes product candidates and preclinical products under development in various stages of development. Details of the company’s pipeline and collaborations are as follows: FDA-Approved PF708 Product In October 2019, the FDA approved the NDA for PF708 under the 505(b)(2) regulatory pathway, with Forteo (teriparatide injection) as the reference drug. The FDA-approved PF708 product is indicated for the treatment of osteoporosis in certain patients at high risk for fracture. The FDA-approved PF708 product would be commercialized and manufactured in the U.S. by the company’s collaboration partner, Alvogen. In November 2019, the company transferred the NDA to Alvogen pursuant to its collaboration agreement. Alvogen intends to launch the FDA-approved PF708 product in the U.S. upon an FDA decision on the therapeutic equivalence evaluation of the product. The FDA approval of the FDA-approved PF708 product was supported by data from Study PF708-301, which compared the effect of PF708 and Forteo in osteoporosis patients. The PF708-301 study enrolled a total of 181 patients, with 90 patients receiving PF708 and 91 patients receiving Forteo. Eighty-two patients completed the study in the FDA-approved PF708 product treatment group, compared with 81 patients in the Forteo treatment group. The primary study endpoint was anti-drug antibody incidence after 24 weeks of drug treatment. The secondary study endpoints included mean percentage changes in lumbar-spine bone mineral density and median percentage changes in bone turnover markers after 24 weeks of drug treatment, as well as pharmacokinetic parameters for approximately four hours after the first dose. Safety endpoints were incidences of adverse events and serious adverse events. The PF708-301 study showed comparable overall profiles between PF708 and Forteo across multiple endpoints. These results from the PF708-301 study, along with bioequivalence findings from Study PF708-101 in healthy subjects, supported the PF708 NDA submitted in December 2018 pursuant to the 505(b)(2) pathway. In October 2019, the NDA was approved by the FDA. In addition to obtaining FDA approval of PF708, the company has been continuing its efforts to obtain an ‘A’ therapeutic equivalence designation for the product relative to its reference drug, Forteo. A determination of therapeutic equivalence might permit the FDA-approved PF708 product to be automatically substituted for Forteo, depending on applicable laws and policies within each of the 50 states in the U.S. Consistent with the company’s interactions with the FDA and the agency’s draft guidance document on comparative use human factors studies for demonstrating the therapeutic equivalence of drug-device combination products, the company successfully completed the PF708 comparative use human factors study and submitted the final study report to the FDA in October 2019. The study data demonstrate that the user interface of the FDA-approved PF708 product was noninferior to that of Forteo for each critical user task evaluated in the study based on a pre-specified statistical analysis of critical patient and caregiver tasks. In February 2019, the company and Alvogen expanded its collaboration, granting Alvogen rights to commercialize and manufacture PF708 in the European Union (EU), certain countries in the Middle East and North Africa (MENA), and the rest of the world territories (the latter defined as all countries outside of the EU, the U.S., and MENA, excluding Mainland China, Hong Kong, Singapore, Malaysia and Thailand). Alvogen submitted a centralized application to the European Medicines Agency (EMA) for PF708 on May 6, 2019, and the filing was accepted by the EMA on May 23, 2019. PF708 could be approved in the EU as early as the second half of 2020, pending marketing authorization by the European Commission under the EU centralized procedure and other factors. In October 2019, Alvogen’s partner SAJA, submitted a MAA for PF708 to the Kingdom of Saudi Arabia's Saudi Food and Drug Authority (SFDA). Subject to applicable regulatory approvals, PF708 would be commercialized in Europe and other jurisdictions by Alvogen’s commercialization partners and including Theramex in Europe, SAJA, a Tamer Group company in MENA, JAMP Pharma in Canada, Kamada Ltd. in Israel, and Pharmbio Korea, Inc. in South Korea. Alvogen is responsible for overseeing any clinical development, regulatory, litigation, commercial manufacturing or commercialization activities of its partners in these jurisdictions. In April 2018, the company and China NT Pharma Group Company Ltd. (NT Pharma) entered into a development and license agreement, pursuant to which the company granted a license to NT Pharma to commercialize PF708 in Mainland China, Hong Kong, Singapore, Malaysia and Thailand; and a non-exclusive license to conduct development activities in such territories with respect to PF708. NT Pharma is responsible for any further development required to achieve regulatory approval, as well as commercialization activities in the applicable territories. In May 2019, the company entered into an agreement with Alvogen for the company to provide PF708 drug substance batches. This product sold to Alvogen was initially manufactured by the company’s contract manufacturing organization for manufacturing process validation purposes as part of the PF708 NDA submission to the FDA for approval. Jazz Collaboration – Multiple Hematologic Oncology Product Candidates The company has a license and option agreement with Jazz, pursuant to which the company and Jazz are developing hematologic oncology products, including PF743 (JZP-458), a recombinant Erwinia asparaginase, and PF745 (JZP-341), a long-acting recombinant Erwinia asparaginase; and Jazz would have the right to manufacture and commercialize such products worldwide. In addition, pursuant to the agreement, the company has granted Jazz certain other rights to negotiate the right to develop, manufacture, and commercialize worldwide other hematologic oncology products that are developed by the company. Both PF743 (JZP-458) and PF745 (JZP-341) are being developed for the treatment of ALL and other hematological malignancies. In August 2019, Jazz reported that they completed a Phase 1 study for PF743 (JZP-458). After receiving Fast Track designation from the FDA in October 2019, Jazz announced the initiation of a Phase 2/3 pivotal study for PF743 (JZP-458) in December 2019 and recently announced their intent to submit a biologics license application with the FDA as early as the fourth quarter of 2020. CRM197 The company has both licenses and supply agreements in place for CRM197, which is a non-toxic mutant of diphtheria toxin. It is a well-characterized protein and functions as a carrier for polysaccharides and haptens, making them immunogenic. The company has developed CRM197 production strains based on its Pfenex Expression Technology platform. As a result of its development efforts, the company previously entered into commercial licenses for production strains capable of producing CRM197 with both Merck and SIIPL. Merck and SIIPL are using the CRM197 produced through the licensed production strain in multiple clinical and pre-clinical stage products. The clinical stage products include Merck’s 15-valent pneumococcal conjugate vaccine, PCV-15 (V114), in various ongoing Phase 3 clinical studies, and SIIPL’s 10-valent pneumococcal conjugate vaccine, Pneumosil, which achieved WHO Prequalification in December 2019, and a pentavalent meningococcal conjugate vaccine in a Phase 3 clinical study. The CRM197 production strains utilized by both Merck and SIIPL are licensed to each party. Additionally, as part of the SIIPL commercial license agreement, SIIPL supplies both reagent grade and cGMP (current Good Clinical Practice) CRM197 to Pfenex, which supplies the product to vaccine development-focused pharmaceutical partners. Arcellx Development, Evaluation and License Agreement The company previously entered into a development, evaluation and license agreement with Arcellx, which provides access to the Pfenex Expression Technology platform to advance Arcellx’s proprietary sparX proteins that activate, silence and reprogram Antigen-Receptor Complex T cell-based therapies. The company has completed the development of both sparX-1 (PF753) and sparX-2 (PF754), and Arcellx has opted into the commercial license for both production strains. Other Pipeline Products In the third quarter of 2019, the company added PF810, a peptide based next generation therapeutic, to its wholly owned pipeline. PF810 is in preclinical development. Collaborations, Joint Development and Licenses The Dow Chemical Company The company has a series of agreements with Dow Global Technologies LLC and/or The Dow Chemical Company, or collectively, Dow, including a technology assignment agreement, a technology licensing agreement, and a grant-back and technology license agreement. Under the technology assignment agreement, Dow assigned to the company certain patents, know-how and trademarks relating to its Pfenex Expression Technology. Under the grant-back and technology license agreement, the company granted to Dow exclusive and non-exclusive licenses under certain patents and know-how relating to its Pfenex Expression Technology to use certain biological materials to make, use and commercialize products in certain fields of use that do not include human therapeutics. The U.S. Department of Health and Human Services (HHS) The development of Px563L and RPA563 is funded by the HHS through the Biomedical Advanced Research and Development Authority (BARDA). In March 2019, the company received a notice from BARDA advising it of BARDA’s decision not to exercise development options for cGMP manufacturing, preclinical studies and Phase 1/2b study readiness in connection with the company’s Px563L and RPA563 novel anthrax vaccine program. Following the receipt of the notice from BARDA and pursuant to discussions with BARDA, the company deprioritized this program in its portfolio. Customers As of December 31, 2019, the company had generated revenue from government contracts, service agreements, collaboration agreements, and reagent protein product sales. For the year ended December 31, 2019, Jazz and Alvogen each accounted for approximately 10% of the company’s revenue. Government Regulation FDA regulations require investigation and correction of any deviations from cGMPs and impose reporting and documentation requirements upon the company and any third-party manufacturers that the company might decide to use. Intellectual Property As of December 31, 2019, the company was the sole owner of a patent portfolio that consisted of a total of 24 U.S. issued patents and six U.S. non-provisional patent applications that provide material coverage for its platform technology and its major product candidates, as well as foreign granted and pending patent applications, which are counterparts to certain of the foregoing U.S. patents and patent applications. The company’s U.S. issued patents expire during the time period beginning in 2023 and ending in 2036. Strategy The company’s strategy is to leverage its Pfenex Expression Technology protein production platform and product development infrastructure to become a major biotechnology company focused on developing a portfolio of wholly-owned and partnered novel and next generation therapeutics. The key elements to execute on the company’s strategy include three focus areas, such as advancing core products and partnerships (improve PF708’s commercial potential, advance the Jazz partnered programs, and expand its portfolio of license and supply relationships for its CRM197 vaccine carrier protein); selectively adding wholly owned next generation therapeutics and partnerships where its platform is uniquely adding wholly owned next generation therapeutic programs and establishing additional product development partnerships); and expanding into the development of novel biologics based on targeting validated biological targets with novel modalities in select disease areas (advance novel modalities via a third-party collaboration). Research and Development The company’s research and development expenses were approximately $25.5 million in 2019.