SANTA CLARA (AP) — San Francisco 49ers running back Jerick McKinnon had another setback in his return from a knee injury.

General manager John Lynch told flagship radio station KNBR on Wednesday that McKinnon’s return to practice the previous day was “not encouraging.” Lynch said McKinnon’s recovery regressed for the third time this summer as he has tried to get back on the field.

McKinnon tore his right ACL a week before the start of last season. He had a flare-up right before the start of training camp and began on the physically unable to perform list. McKinnon was activated on Aug. 6 and went through two light practices before another setback sidelined him for three weeks.

McKinnon returned to practice again Tuesday but had another setback.

“It’s a real bummer because you keep getting to the final step and the final step is actually playing NFL football, and particularly at his position, where you have to make hard cuts, you have to put your foot in the ground, and we did it a month ago and he kind of regressed and I would say yesterday we had a similar situation,” Lynch told the radio station. “So we’re trying to get to what’s the root cause of the problem that he’s having. And just because he’s working through it, I’m going to leave it at that, but yesterday was not encouraging from that standpoint for Jet. What that means, we’re not sure yet, but we’re working hard to find that out.”

The Niners could place McKinnon on season-ending injured reserve or put him on the initial 53-man roster Saturday and then place him on IR, leaving the option for him to return after eight weeks.

McKinnon was one of the team’s major acquisitions in free agency in 2018, signing a four-year, $30 million contract but he has yet to play a game for San Francisco because of injuries.

The 49ers have depth at running back with free-agent acquisition Tevin Coleman having the most playing experience over his career. He has been a key part of Atlanta’s offense the past few years.

Matt Breida, who averaged 5.3 yards per carry last season, had seven carries for 44 yards and a 20-yard TD catch last week against Kansas City and also figures to be in the rotation.

Special teams standout Raheem Mostert has also fared well as a running back this preseason with 100 yards from scrimmage at Denver in San Francisco’s second exhibition game.

Reserve Jeff Wilson has also played well with 21 carries for 78 yards and three TDs in the preseason but San Francisco might not have room for four running backs on the roster.

In other injury news, Lynch said No. 2 overall pick Nick Bosa could possibly return as early as the season opener against Tampa Bay on Sept. 8 from an ankle injury. 

The defensive end sprained his ankle in practice on Aug. 7.