Genmab


Genmab A/S is a Danish biotechnology company, founded in February 1999 by Florian Schönharting, at the time managing director of BankInvest Biomedical venture fund. Genmab is based in Copenhagen. Internationally, it operates through the subsidiaries Genmab BV in Utrecht, The Netherlands, and Genmab, Inc in Princeton, New Jersey, USA. The Company is publicly traded on the Copenhagen Stock Exchange.
The company has two approved antibodies, Arzerra® for the treatment of certain chronic lymphocytic leukemia indications and DARZALEX™ 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. They also have a broad clinical and pre-clinical product pipeline.

Technology

Genmab's technology is licensed from Medarex to create fully human high affinity antibodies using transgenic mice. These antibodies are less likely to elicit an allergic reaction and other side effects compared with other types of man-made antibodies containing other animal proteins because the IgG antibodies produced have human proteins. This technology is called the HuMab-Mouse technology. One benefit of using this type of technology is that there is no need for humanization or complicated genetic engineering to make this antibody fit for humans which cuts down on expenses and time spent developing it. It can be generated within months and can be selected to bind to specific antigens such as tumor cells and other infectious agents.
Genmab also has developed its own technology called UniBody, which is used to make smaller antibodies in contrast to the traditional full sized monoclonal antibody. Its smaller size allows for better distribution over larger target areas like tumors. The UniBody can only bind to one site and doesn’t elicit a harmful immune response by binding to two sites and over-activating cell growth. It does not kill target cells but rather silences or inhibits them. Thus it can be used to treat certain cancers, inflammations, allergies and asthmas, where killing the cell isn’t the objective.
The technology modifies the human IgG4 antibody. Normally the IgG4 is considered inert and doesn’t elicit an immune response. However, they are also unstable and fall apart easily, which makes them unsuitable for therapeutic use. Genmab changes the shape of the IgG4 antibody by eliminating the hinge, the part of the antibody that creates the “Y” shape. This halves the antibody, creating a smaller version now known as their UniBody. This smaller version can only bind to one site and does not stimulate cancer cells to grow.

History of the Company

Genmab was founded as a European spin-off of American Biotech company Medarex in February 1999. Danish investment firm BankInvest, under Florian Schönharting, provided the seed investment for the company to start up in Copenhagen. Like Medarex, Genmab began work producing monoclonal antibodies for life-threatening or debilitating diseases. Rising quickly in the Biotech world, Genmab attracted many investors, especially venture capital firms. The company went public in October 2000, earning DKK 1.56 billion, and had a second public offering in January 2006 yielding DKK 800 million.
The company's initial R&D location was a nine-story building in Utrecht Science Park, in the Netherlands; this was replaced with an "R&D Center" also in Utrecht, in June 2018. By mid-2019, this new facility was at capacity, and plans were set afoot to build an adjacent, connected facility.
By 2001, Medarex and Genmab had come back together in a drug development partnership, which highlighted the manufacturing deficit and clinical development expertise of Genmab relative to Medarex.
In 2005 the Biotechnology Industry Organization and the Long Island Life Sciences Initiative honored Genmab with a James D. Watson Helix Award.
2008 saw the company purchasing a 22,000-litre, 36-acre antibody manufacturing plant in Brooklyn Park, Minnesota from PDL BioPharma, with plans to retain all 170 employees thereat. However, the company ran into financial trouble originating from several quarters, and a decision to sell the facility was reached in late 2009, after Genmab had started producing development scale batches from the facility. In 2008, the world was experiencing a financial crisis as a whole, and GlaxoSmithKline decided to exit oncology, which impacted co-development of ofatumumab, an oncology-directed product. In tandem with the sale of the plant, the company reorganized and planned to dismiss about 300 employees. Selling the facility, though, proved very difficult, due in large part to the global financial crisis; by 2012, Genmab had decided to simply write-off the entire facility from the company's balance sheets. A sale of the facility to Baxter came in February 2013.
Following the failed strategy of in-housing manufacturing, Genmab chose to thereafter completely outsource both manufacturing and the conduct of clinical trials.
The Company's first product, Arzerra reached the US market in 2009 for refractory chronic lymphocytic leukemia.
By 2019, the company had three core sites, located in Copenhagen, Princeton and Utrecht.

Executive history

Lisa N. Drakeman, Ph.D. had been a vice president at Medarex and wife of Donald Drakeman, Medarex's CEO and President at the time. Drakeman was one of Genmab's co-founders and was appointed chief executive officer of the company upon incorporation in 1999, also joining the board of directors. , Drakeman remained in the CEO role, but by 2010 she had announced her retirement.
In 2010 Jan Van de Winkel, a co-founder of the firm, was appointed as President and CEO of Genmab. Since the company started in 1999, he had been Genmab's chief scientific officer ; he had concurrently served as head of research, then president of R&D. , Van de Winkel remained CEO of the firm. Van de Winkel is a scientist, having produced more than 300 publications during his career.

Partnerships

Amgen: In May 1999, Genmab entered a sub-license agreement with Amgen where it would gain rights to the IL15 antibodies. In October 2001, this was replaced by a direct license agreement where Amgen retained exclusive commercialization options for the products through phase II. Amgen has also expanded its agreement to a new antibody program targeting additional disease targets. Amgen has discontinued development of the IL15 antibody, AMG 714, in psoriasis and rheumatoid arthritis based on disappointing results from recent clinical studies. Amgen is exploring options to maximize the value of this asset, but as this time, no further internal development of a lead indication is planned.
GlaxoSmithKline: In December 2006, Genmab entered a deal with GlaxoSmithKline to co-develop and commercialize ofatumumab, a drug that could be used for treatment in CD20 positive B-cell chronic lymphocytic leukemia, follicular non-Hodgkin’s lymphoma, rheumatoid arthritis and other indications. The agreement gave Genmab a license fee of DKK 582 million and GSK bought 4,471,202 shares of Genmab for DKK 2,033 million. The potential value of this agreement could be DKK 12.0 billion if all milestones are reached and commercial success is reached in the fields of cancer, autoimmune, and inflammatory disease. The intention of GlaxoSmithKline to exit oncology, disagreement around milestones reached, and financial difficulties of Genmab, led to re-negotiation of the partnership in mid-2010, resulting in an immediate payment by GlaxoSmithKline and future financial and licensing concessions on the part of Genmab.
In addition, Genmab has collaborations with Roche, Lundbeck and Seattle Genetics.

Clinical pipeline

Status of Genmab's clinical pipeline, as of November 2015.
ProductDisease IndicationsPhasePartner
Daratumumab Multiple MyelomaApprovedJanssen
Ofatumumab Chronic lymphocytic leukemiaApprovedGlaxoSmithKline
OfatumumabFollicular lymphomaIIIGlaxoSmithKline
OfatumumabDiffuse large B-cell lymphomaIIIGlaxoSmithKline
OfatumumabPemphigus vulgarisIIIGlaxoSmithKline
OfatumumabRelapsing Remitting Multiple SclerosisIIoriginally GlaxoSmithKline; Novartis
OfatumumabWaldenstrom’s MacroglobulinemiaIIGlaxoSmithKline
HuMax-TF-ADCCancerISeattle Genetics
TeprotumumabGraves' ophthalmopathyBLA filed with FDA, July 2018originally River Vision; Horizon
TeprotumumabDiabetic macular edemaIRiver Vision
Enapotamab Vedotin Seattle Genetics and US National Cancer Institute

Teprotumumab was originally developed with Roche for cancer, but it failed in that indication; Roche subsequently licensed to River Vision. At least part of the rights to the antibody are now in the hands of Horizon Pharma.