• Daratumumab receives Break­through Therapy Desig­na­tion in com­bi­na­tion with standard of care regi­mens for multiple myeloma patients who have received at least one prior line of ther­apy
• Potential for accelerated review
• Marks second Break­through Therapy Desig­na­tion for dara­tu­mu­mab

{{image}}Copenhagen, Denmark (Press Release) — Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the U.S. Food and Drug Admin­istra­tion (FDA) has granted Break­through Therapy Desig­na­tion for DARZALEX^® (dara­tu­mu­mab) injection in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, or bor­tez­o­mib and dexa­meth­a­sone for the treat­ment of patients with multiple myeloma who have received at least one prior ther­apy. Break­through Therapy Desig­nation is a pro­gram in­tended to expedite the devel­op­ment and review of drugs to treat serious or life-threatening diseases in cases where pre­lim­i­nary clin­i­cal evi­dence shows that the drug may provide sub­stan­tial im­prove­ments over avail­able ther­apy. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive world­wide license to develop and com­mer­cial­ize dara­tu­mu­mab.

"This is the second time dara­tu­mu­mab has earned the distinction of a Break­­through Therapy Desig­nation. We are pleased that the FDA con­tinues to recog­nize the poten­tial of dara­tu­mu­mab to help patients with multiple myeloma. We con­tinue to work with our strategic partner Janssen and the regu­la­tory author­i­ties to ad­vance dara­tu­mu­mab to bring this treat­ment to more patients suffering from multiple myeloma as quickly as possible," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The Break­through Therapy Desig­na­tion for dara­tu­mu­mab was granted on the basis of data from two Phase III studies: CASTOR (MMY3004; NCT02136134) eval­u­ating dara­tu­mu­mab in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone versus bor­tez­o­mib and dexa­meth­a­sone alone in patients with re­lapsed or refractory multiple myeloma, and POLLUX (MMY3003; NCT02076009) eval­u­ating dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone versus lena­lido­mide and dexa­meth­a­sone in patients with re­lapsed or refractory multiple myeloma.

About Break­through Therapy Desig­na­tion

The Break­through Therapy Desig­na­tion was enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA) and is in­tended to expedite devel­op­ment of drugs to treat serious and life-threatening medical con­di­tions when pre­lim­i­nary clin­i­cal evi­dence dem­onstrates that the drug may have sub­stan­tial im­prove­ment on at least one clin­i­cally sig­nif­i­cant end­point over avail­able ther­a­pies. Break­through Therapy Desig­na­tion in­cludes all the features of the Fast Track Desig­na­tion, as well as more intensive guidance from the FDA on a drug's clin­i­cal devel­op­ment pro­gram.

About DARZALEX® (dara­tu­mu­mab)

DARZALEX® (dara­tu­mu­mab) injection for in­tra­venous in­fusion is indicated in the United States for the treat­ment of patients with multiple myeloma who have received at least three prior lines of ther­apy, in­­clud­ing a pro­te­a­some inhibitor (PI) and an immuno­modu­la­tory agent, or who are double-refractory to a PI and an immuno­modu­la­tory agent.¹ DARZALEX is the first mono­clonal anti­body (mAb) to receive U.S. Food and Drug Admin­istra­tion (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as mono­therapy for the treat­ment of adult patients with re­lapsed and refractory multiple myeloma, whose prior ther­apy in­cluded a PI and an immuno­modu­la­tory agent and who have dem­onstrated disease pro­gres­sion on the last ther­apy. For more in­­for­ma­tion, visit www.DARZALEX.com.

Daratumumab is a human IgG1k mono­clonal anti­body (mAb) that binds with high affinity to the CD38 molecule, which is highly ex­pressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through pro­grammed cell death, or apop­tosis,^1,2 and multiple immune-mediated mech­a­nisms, in­­clud­ing complement-dependent cyto­tox­icity,^1,2 anti­body-dependent cellular phago­cytosis^3,4 and anti­body-dependent cellular cyto­tox­icity.^1,2 In addi­tion, dara­tu­mu­mab ther­apy results in a reduction of immune-suppressive myeloid derived sup­pressor cells (MDSCs) and subsets of regu­la­tory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs and Bregs were accompanied by in­­creases in CD4+ and CD8+ T cell numbers in both the periph­eral blood and bone marrow.^1,5

Daratumumab is being devel­oped by Janssen Biotech, Inc. under an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize dara­tu­mu­mab from Genmab. Five Phase III clin­i­cal studies with dara­tu­mu­mab in re­lapsed and frontline settings are cur­rently ongoing, and addi­tional studies are ongoing or planned to assess its poten­tial in other malignant and pre-malignant diseases on which CD38 is ex­pressed, such as smol­der­ing myeloma, non-Hodgkin's lym­phoma and a solid tumor indi­ca­tion.

About Genmab

Genmab is a publicly traded, inter­na­tional bio­technology com­pany specializing in the creation and devel­op­ment of dif­fer­en­ti­ated anti­body thera­peutics for the treat­ment of cancer. Founded in 1999, the com­pany has two approved anti­bodies, Arzerra® (ofatumumab) for the treat­ment of certain chronic lym­pho­cytic leukemia indi­ca­tions and DARZALEX® (dara­tu­mu­mab) for the treat­ment of heavily pre­treated or double refractory multiple myeloma. Dara­tu­mu­mab is in clin­i­cal devel­op­ment for addi­tional multiple myeloma indi­ca­tions and for non-Hodgkin's lym­phoma. Genmab also has a broad clin­i­cal and pre-clinical prod­uct pipe­line. Genmab's tech­nology base consists of val­i­dated and pro­pri­e­tary next generation anti­body tech­nolo­gies - the DuoBody® plat­form for generation of bispecific anti­bodies, and the HexaBody® plat­form which creates effector function en­hanced anti­bodies. The com­pany in­tends to leverage these tech­nolo­gies to create oppor­tu­ni­ties for full or co-ownership of future prod­ucts. Genmab has alliances with top tier pharma­ceu­tical and bio­technology com­pa­nies. For more in­­for­ma­tion visit www.genmab.com.

This Company Announcement con­tains for­ward looking state­ments. The words "believe", "expect", "antic­i­pate", "intend" and "plan" and similar ex­pres­sions identify for­ward looking state­ments. Actual results or per­for­mance may differ ma­teri­ally from any future results or per­for­mance ex­pressed or implied by such state­ments. The im­por­tant factors that could cause our actual results or per­for­mance to differ ma­teri­ally in­clude, among others, risks asso­ci­ated with pre-clinical and clin­i­cal devel­op­ment of prod­ucts, un­cer­tain­ties related to the out­come and conduct of clin­i­cal trials in­­clud­ing un­fore­seen safety issues, un­cer­tain­ties related to prod­uct manu­fac­tur­ing, the lack of mar­ket acceptance of our prod­ucts, our in­abil­ity to man­age growth, the competitive en­viron­ment in rela­tion­ to our business area and mar­kets, our in­abil­ity to attract and retain suitably qualified per­son­nel, the un­en­force­ability or lack of protection of our patents and pro­pri­e­tary rights, our rela­tion­ships with affiliated entities, changes and devel­op­ments in tech­nology which may render our prod­ucts obsolete, and other factors. For a further discussion of these risks, please refer to the risk man­agement sections in Genmab's most recent financial reports, which are avail­able on www.genmab.com. Genmab does not under­take any obli­ga­tion to update or revise for­ward looking state­ments in this Company Announcement nor to con­firm such state­ments in rela­tion­ to actual results, unless required by law.

Genmab A/S and its sub­sid­i­aries own the fol­low­ing trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in com­bi­na­tion with the Y-shaped Genmab logo™; the DuoBody logo®; the HexaBody logo™; HuMax®; HuMax-CD20®; DuoBody®; HexaBody® and UniBody®. Arzerra® is a trademark of Novartis AG or its affiliates. DARZALEX® is a trademark of Janssen Biotech, Inc.

References

1. DARZALEX Prescribing Information, November 2015.
2. De Weers, M, et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. 2011; 186: 1840-1848.
3. Overdijk, MB, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015; 7: 311-321.
4. Khagi, Y and Mark, TM. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095—1100.
5. Krejcik, MD et al. Daratumumab Depletes CD38+ Immune-regulatory Cells, Promotes T-cell Expansion, and Skews T-cell Repertoire in Multiple Myeloma. Blood. 2016; pii: blood-2015-12-687749. [Epub ahead of print].

Source: Genmab.