EP Vantage Interview - ACT heads for the clinic with second stem cell-based therapy

For a company well into its second decade of existence, Advanced Cell Technology (ACT) has enjoyed greater success generating headlines than developing commercial breakthroughs. Announcements about the successful cloning of animals and its work with human embryonic stem cells might have garnered the company a great deal of attention and were no doubt important scientifically, however, in terms of clinical progress, it has only one project in very early stage human trials.

This arguably does not represent great progress for a public company, however, according to William Caldwell, the company’s chief executive, translating ACT’s science into commercial products is now the key focus. A couple of events on the horizon could well set the wheels in motion in this regard. Before the end of the year permission will be sought from US regulators to begin human trials with its second stem cell-based therapy, whilst a partner is being sought for a programme that is ready to commence phase II, Mr Caldwell told EP Vantageat BIO Europe last week, where he had travelled to sound out any interested parties.

High risk

Despite the loosening of funding restrictions in the US last year, the stem cell field remains at the very high risk end of drug discovery. For those companies that have appeared on the public markets, such as Geron, StemCells and ACT, their shares rocket and plummet with every hype and disappointment; unfortunately the latter seems to be more common.

Mr Caldwell believes that the project ACT hopes to advance into the clinic next year has a good chance of receiving the blessing of regulators, for several reasons. The programme is investigating the use of retinal pigment epithelium (RPE) cells, which will be injected into the eye of the patient to treat age-related macular degeneration and other eye diseases.

The company has managed to derive RPE cells from a stable human embryonic stem cell line. Because they are terminally differentiated, meaning they cannot change into any other sort of cell, this should lower, if not eliminate, the risk of tumours developing, a big concern for these types of therapies.

Additionally, the amount of cells injected into the patient is relatively small compared to other cell therapies, meaning it is easier to track where the cell ends up. Because the eye is enclosed they should not move anyway, Mr Caldwell said.

There is no risk of rejection because the eye is “immune privileged”, and the cells are administered into the eye through injection, a skill that eye surgeons already possess and a simple technique that does not need separate approval.

Turn around

Despite all this, Mr Caldwell admits that the IND is likely to face much greater scrutiny than normal.

“I’m not looking for a 30 day turnaround. But by the end of the first quarter we should know our fate. We want to be in the clinic by the third quarter,” he said.

The programme that Mr Caldwell is seeking to partner is more complex. The company plans to deliver autologous skeletal myoblasts, adult stem cells derived from the patient, into the scarred heart tissue of patients with severe heart failure. FDA approval has been received for a phase II trial, following successful phase I work which established the therapy was safe.

The phase II trial will probably recruit around 80 patients, and attempt to establish whether heart failure symptoms can be improved.

Funding hurdle

This progress is certainly encouraging, however funding is a massive future hurdle for the company. According to accounts filed with the SEC in July, ahead of the transfer of the company’s stock from the thinly regulated Pink Sheets to the Nasdaq’s over-the-counter bulletin board, the company ended March with just $522,502.

Mr Caldwell said that funding options are also being explored, and SEC filings indicate that earlier this month the company filed to raise $2m in a share sale. Shares in the company are currently trading at 10 cents, giving the group a market value of $50m.

The diminutive market values of most stem cell companies largely reflects the early stage of this area, however Mr Caldwell believes that a greater urgency is needed, particularly in the stem cell field, to move science into manufacturing phase.

"We need more focus on the translation, and get into development mode. There has been no sense of urgency," he said, calling for greater business accumen to enter the arena.

However, for that progress to happen at ACT, cash or partners, or both, are needed fast.