The current head of 'The Family'--a secret Government of officials who have been controlling and manipulating the events of the Western world for centuries--on the surface Derek works as a confidant and aid to President Adam Benford. However, after he learns that Adam is planning to unveil the 'truth' concerning the Raccoon City Incident, Derek then instigates a B.O.W. outbreak in Tall Oaks when Adam travels over to give a speech.
Blackmailing Secret Service agent Helena Harper by kidnapping her sister, she reluctantly steps aside and abandons her post allowing the outbreak to occur. This then begins Leon S. Kennedy's campaign.
Derek was initially employing Ada Wong's services as a spy and eventually began to grow an immense fascination with her. However, after Ada Wong learned that Derek was responsible for the destruction of Raccoon City, she quickly removed herself from his company. Derek on the other hand still felt a strong emotional attachment towards Ada and desperately wanted her to return. Because he was unable to have her return to him, he then decided to create a clone of her. Selecting his best researcher, Carla Radames, as his unwilling test subject, along with Ada Wong's DNA and the C-Virus, he then managed to create an almost perfect clone of Ada Wong.
However, despite inheriting her personality, Carla deep down became aware of who she used to be and what had happened. This revelation infuriated her. Intending to destroy the very World that The Family had created, she then began using her C-Virus to incite chaos across Edonia and eventually China. This series of events then spark into motion the beginning of Jake Muller and Chris Redfield's campaigns.
While Simmons is the reason behind the conflict across all four of the campaigns, he only primarily stars in Leon S. Kennedy's campaign, while also making brief appearances in Jake Muller's and Ada Wong's.
Simmons makes his first physical appearance during a flashback recalled by Helena, as both she and her sister Deborah are tied to a chair, and Deborah is taken away as leverage for her cooperation in the assassination of the President. It isn't until the end of Leon's Chapter 3 that he is introduced into the story. Because Helena knows that Derek is behind the Tall Oaks outbreak, and the eventual bombing of the Town, she along with Leon travel to China to track Simmons down and bring him to justice.
Once they first manage to catch up to him, he and his bodyguards begin firing upon the two. Sherry Birkin, who was sent on a mission to retrieve Jake Muller and escort him to Derek because of his natural immunity to viruses--unbeknownst to her that Derek actually wants Jake's blood so as to further his experiments--also then arrives soon after along with Jake. With the four hunkered behind a wall, Leon and Helena then begin returning fire at Simmons and his men so as to cause a distraction for Jake and Sherry while they escape.
During this time, Simmons is then injected by an enhanced variant of the C-Virus by a J'avo sent by Carla Radames. As the virus slowly begins to take effect, he falls down onto a passing train as Leon and Helena give chase. While on the train, Simmons then begins to transform into a large, fleshy, monstrous canine; during this time, operatives of The Family riding a helicopter spot the infected Simmons and abandon him. After an arduous battle, Simmons is temporarily put down after he's run over by the train.
However, he soon returns once more inside a large hall of an office building and goes through another mutation - this time morphing him into what resembles a tyrannosaurus. Leon and Helena, along with Ada flying in an attack chopper, are once again able to beat him. Ada then flies off and leaves the helicopter, along with an RPG and the evidence to indite Simmons of his crimes, for Leon and Helena. During her own escape, however, Simmons returns yet again and begins to do battle with Ada. Meanwhile Leon and Helena, after their elevator is destroyed forcing them to climb to the top floor of the building via rope, notice a wounded Ada as Simmons advances, leading Leon to then dive down to help her while Helena provides support from above.
The trio manage to beat Simmons, who has now taken to his original canine form again, for the third time as Ada knocks him off, while he temporarily reverts back to his humanoid form, into a raging fire below. Ada leaves the scene and alerts Leon about the helicopter above. The two then continue upwards towards the helipad, but once again Simmons returns. Weakened from their last fight, Simmons absorbs the zombies around the area to feed and heal himself. Leon and Helena slip past after Simmons is then attacked by a horde of zombies who attempt to devour him.
Reaching the helipad, the seemingly invincible Simmons arrives on their tail. Now in his third mutation, he has taken the form of what looks like a giant fly. Regardless, Leon and Helena are able to weaken Simmons enough to reach the helicopter and shoot him down with the RPG. Simmons, now in his humanoid form, then lands onto a large, sharp ornament below and finally dies for good.