Contributions to Approved Therapeutics and Therapeutic Candidates

Randy Schreckhise

APPROVED:

Tretten® (Coagulation Factor XIII A-Subunit, Recombinant)
A recombinant analogue of human Factor XIII A-subunit indicated for the prevention of bleeding in the rare clotting disease Congenital Factor XIII A-subunit deficiency. Factor XIII was initially developed by ZymoGenetics and licensed to Novo Nordisk in 2004 after completion of Phase 1 studies.
2000 – 2005 (ZymoGenetics)
Production of research reagents, including proteins and antibodies, and contributions to the CMC sections of the IND and BLA.

Recothrom® (Thrombin topical, Recombinant)
A topic thrombin spray/patch indicated to aid hemostasis during post-surgical bleeding. Developed to replace a fifty year old marketed drug derived from cow blood. Recothrom was approved by the FDA in 2008, and was divested by Bristol-Myers Squibb following their acquisition of ZymoGenetics in 2010 (now marketed by Baxter).
2000 – 2005 (ZymoGenetics)
Production of research reagents, including proteins and antibodies, and contributions to the CMC sections of the IND and BLA.

Benlysta® (Belimumab)
A fully-human antibody discovered through Cambridge Antibody Technology’s phage display library, which binds the B-cell activating factor BLyS. Benlysta was approved in the US in 2011 for the treatment of Systemic Lupus Erythematosus. GSK acquired the asset following the purchase of Human Genome Sciences in 2012.
2008 – 2010 (Human Genome Sciences)
Budgeting, Forecasting and Strategic Planning for Phase 3 program and commercial launch.

Raxibacumab® (ABthrax)
A fully-human antibody discovered through Cambridge Antibody Technology’s phage display library, which targets the major antigen of the bacterium Bacillus antracis. Raxibacumab was approved in the US in 2012 for the treatment of inhalation Anthrax, and developed by Human Genome Sciences under a contract with the Biomedical Advanced Research and Development Authority. GSK acquired the asset following the purchase of Human Genome Sciences in 2012.
2008 – 2010 (Human Genome Sciences)
Budgeting, Forecasting and Strategic Planning.

Sivextro® (Tedizolid Phosphate)
An oxazolidinone-class antibiotic approved in the US to treat acute bacterial and skin structure infections caused by gram-positive infections. Trius Therapeutics in-licensed the Phase 1 stage asset TR-701 from South Korean pharmaceutical company Dong-A, and subsequently out-licensed the Ex-Americas and Ex-European rights to Bayer following a successful Phase 2 program. Trius was acquired prior to the NDA submission in 2013 by Cubist Pharmaceuticals. Sivextro was approved by the FDA in 2014, and is now marketed by Merck, following their acquisition of Cubist.
2012 – 2013 (Trius Therapeutics)
Finance representative on Project Core Team.
Clinical Sourcing, Budgeting, Forecasting and Strategic Planning for Phase 3 program and commercial launch.

Zurampic® (Lesinurad)
A selective uric acid re-absorption inhibitor approved by the US FDA in 2015 to treat high levels of uric acid in the blood (hyperuricemia) associated with gout, when used in combination with a xanthine oxidase inhibitor (XOI). Zurampic was discovered and developed by Ardea Biosciences until it’s acquisition by AstraZeneca in 2012. In 2011 Ardea initialed four global Phase 3 clinical trials in gout with Lesinurad. Zurampic is now marketed in the US by Ironwood Pharmaceuticals.
2011 – 2012 (Ardea Biosciences)
Finance representative on Project Core Team.
Clinical Sourcing, Budgeting, Forecasting and Strategic Planning for Phase 3 program and commercial launch.

HALTED LATE STAGE:

Atacicept (TACI-Ig)
Soluble TACI receptor-Ig fusion protein that binds both tumor necrosis factor (TNF) ligand superfamily cytokines APRIL and BLyS, created and initially developed by ZymoGenetics Inc., who licensed worldwide rights to Merck Serono in 2008. Several Phase 2 clinical studies were performed in MS, Systemic Lupus Erythematosus and B-cell malignancies. Merck Serono terminated development after Ph2/Ph3 studies in lupus failed to meet endpoints in 2014.
2000 – 2005 (ZymoGenetics)
Production of research reagents, including proteins, antibodies and genetically modified mice.

Peginterferon lambda-1a (BMS-914143)
Interferon lamda-1a was discovered by and initially developed by ZymoGenetics for the treatment of Hepatitis C. Bristol-Myers Squibb continued clinical development after their acquisition of ZymoGenetics in 2010, and subsequently shelved the program after the Phase 3 program failed to achieve the primary endpoint in HCV.
2000 – 2005 (ZymoGenetics)
Production of research reagents, including proteins, antibodies and genetically modified mice.

Zalbin (Albinterferon Alfa-2b)
An interferon alpha-albumin fusion protein, with an extended six-day half-life developed as a replacement for pegylated interferon alpha-2a treatment of Hepatitis C. Phase 2 studies suggested comparable efficacy, and was the basis for a substantial licensing deal between Human Genome Sciences and Novartis. Potential lung toxicity issues in the Phase 3 program led the DMC to recommend eliminating the high dose arm (1200 mcg) of the study, and to switch all patients on active drug to the lower dose (900 mcg). Although both Ph3 studies met their primary endpoint, the FDA failed to approve the BLA due to concerns regarding the risk/benefit profile of the drug, and the European application was withdrawn. Novartis subsequently returned all development rights to HGS, and HGS discontinued development in 2010.
2008 – 2010 (Human Genome Sciences)
Finance representative on Project Core Team.
Budgeting, Forecasting and Strategic Planning for Phase 3 program and commercial launch.

ONGOING MID/EARLY STAGE

Denenicokin (IL-21, Recombinant/ BMS-982470)
IL-21 was discovered by and initially developed at ZymoGenetics for oncology. Bristol-Meyers Squibb continued development after their acquisition of ZymoGenetics in 2010, and currently has a number of Phase 1 and 2 studies ongoing in both solid tumors and hematologic malignancies.
2000 – 2005 (ZymoGenetics)
Production of research reagents, including proteins, antibodies and genetically modified mice.
2007 – 2008 (ZymoGenetics)
Finance representative on Project Core Team.

RDEA3170
A follow-on to Lesinurad, also a selective uric acid re-absorption inhibitor, currently being studied in several combination and monotherapy Phase 2 gout studies.
2011 – 2012 (Ardea Biosciences)
Finance representative on Project Core Team.

HALTED MID/EARLY STAGE

IL-17RC (Interleukin 17 receptor C)
A Soluble IL-17 ReceptorC-Ig fusion protein that binds both pro-inflammatory cytokines IL-17A and IL-17F, and was initially developed by ZymoGenetics Inc., who licensed worldwide rights to Merck Serono in 2008. Developed was halted in 2010 following tox studies in non-human primates.
2000 – 2005 (ZymoGenetics)
Production of research reagents, including proteins, antibodies and genetically modified mice.
2005 – 2007 (ZymoGenetics)
Research Project Manager from validation and selection of therapeutic agent through indication selection and preclinical development.
2007 – 2008 (ZymoGenetics)
Finance representative on Project Core Team.

Anti-IL31mAb (BMS-981164)
A fully-human antibody discovered through immunization of Medarex’s humanized mice for the treatment of Atopic Dermatitis, which interferes with the inflammatory cytokine IL-31’s ability to bind the receptors Oncostatin M and IL-31RA. ZymoGenetics discovered IL-31 and it’s role in AD. Bristol-Myers Squibb continued development after their acquisition of ZymoGenetics in 2010, and subsequently shelved the program following a Phase 1 study in AD patients in 2014.
2000 – 2005 (ZymoGenetics)
Production of research reagents, including proteins, antibodies and genetically modified mice.

Mapatumumab (HGS-ETR1, HGS1012)
An agonistic, fully-human antibody discovered through Cambridge Antibody Technology’s phage display library. Phase 1 data in 2004 indicated potential utility in treating NHL and solid tumors. In 2008, HGS reported encouraging Ph2 studies with Mapatumumab in Multiple myeloma, however mapatumumab failed to meet the study endpoints in 2010. In 2008 HGS also began two Ph2 studies with Mapatumumab in Non-small-cell lung cancer and Liver cancer. GSK later terminated the Mapatumumab program following the acquisition of HGS after NSCLC and HCC studies failed to meet their primary endpoints in 2011.
2008 – 2010 (Human Genome Sciences)
Finance representative on Project Core Team.
Budgeting, Forecasting and Strategic Planning.

HGS1029 (AEG40826-2HCl)
A potent small molecular inhibitor of IAP family members (XIAP, cIAP-1 and cIAP-2), licensed by Human Genome Sciences from Aegera Thereapeutics in 2007. HGS completed pre-clinical studies and filed an IND in 2008. A Phase I study in hematologic malignancies was completed after failing to reach MTD, while a second study in solid tumors was terminated prior to completion. HGS returned the rights to Aegera in 2012.
2008 – 2010 (Human Genome Sciences)
Finance representative on Project Core Team.
Budgeting, Forecasting and Strategic Planning.