First human dosed with cellular reprogramming drug in longevity trial

A Boston biotech company has administered what researchers are describing as the first human dose of a cellular rejuvenation drug, a milestone in the effort to treat age-related disease at the epigenetic level.

Life Biosciences Inc. announced June 9 that the first participant had been dosed in its Phase 1 clinical trial of ER-100 — the first cellular rejuvenation therapy using partial epigenetic reprogramming to receive FDA clearance to enter human clinical trials. The trial targets optic neuropathies, including open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy, a common cause of sudden vision loss in adults. 

ER-100 is administered by intravitreal injection — directly into the eye — and employs the controlled expression of three of the four Yamanaka factors, the transcription factors OCT-4, SOX-2 and KLF-4, to restore cells to more youthful patterns of gene expression without altering the underlying DNA sequence. 

“This is an important moment for Life Bio and for the field of aging biology,” said David Sinclair, co-founder of Life Biosciences and professor of genetics at Harvard Medical School. “Our research has suggested that aging is driven in large part by the loss of epigenetic information, not irreversible damage. This clinical study represents the first opportunity to test whether restoring that information can ameliorate human disease.” 

ER-100 is administered to one eye and activated by systemic doxycycline for eight weeks. Up to 18 participants are planned for enrollment — 12 with open-angle glaucoma and six with NAION — across four trial sites. Clinics in Boston, New York, Los Angeles and Charleston are recruiting patients. 

Chief Scientific Officer Sharon Rosenzweig-Lipson said preclinical studies demonstrated that controlled expression of the three transcription factors can reset epigenetic patterns associated with healthy cellular function and restore visual function in animal models. 

The eye was selected as the initial trial target for safety reasons. As reported by Nature, changes made to cells in the eye are far less likely to cause dangerous, body-wide side effects than changes made to cells in other organs, making it a natural starting point for techniques scientists hope to apply across the rest of the body.

Not all researchers are convinced the approach is ready for human testing. Neurobiologist Pete Williams at the Centre for Eye Research Australia warned in the journal Nature that a catastrophic outcome could set the entire field back. “If this goes catastrophically wrong, it might screw us all in the future,” Mr. Williams said. 

Cancer risk remains the central safety concern. The same Yamanaka factor genes that researchers believe can reprogram cells have produced teratomas — tumors sometimes found to contain hair, teeth and other partially formed tissue — in earlier experiments. Life Biosciences argues the risk is mitigated by using only three of the four factors and by controlling expression through doxycycline.

Eli Lilly was part of a late-stage $435 million Series C funding round for New Limit, another cellular reprogramming startup, while tech investors Jeff Bezos and Sam Altman have separately backed competing longevity ventures Altos Labs and Retro Biosciences. The Life Biosciences board includes Dr. David Guyer, who serves as president and chief executive of EyeBio, a subsidiary of Merck & Co. 

Life Biosciences closed an $80 million Series D in April to fund the Phase 1 study, with proceeds expected to sustain operations into the second half of 2027. 

The trial does not establish that humans can live longer or that cellular aging can be reversed in tissues outside the eye. It represents the moment at which two decades of laboratory work — including Nobel Prize-winning discoveries by stem cell researcher Shinya Yamanaka and subsequent demonstrations in mice and non-human primates — crosses from animal models into human medicine. 

Mr. Sinclair has separately announced plans to develop an oral version of his reprogramming drugs as his entry in a $101 million XPrize competition, with the grand prize going to the team that can restore roughly 10 years to a patient’s biological age within one year of treatment.