Asterias Provides Update for its AST-OPC1 Phase 1/2a Clinical Trial in Severe Spinal Cord Injury

- Results to Date Show AST-OPC1’s Favorable Safety Profile, Potential for Cell Engraftment and Improved Motor Function -

- Multiple Additional Data Readouts from SCiStar Study Expected in 2018 into First Quarter of 2019 -

- Conference Call and Webcast Today, February 28, at 5:00 p.m. ET –

FREMONT, CA, USA I February 28, 2018 I Asterias Biotherapeutics, Inc. (NYSE American:AST), a biotechnology company dedicated to developing cell-based therapeutics to treat neurological conditions associated with demyelination and cellular immunotherapies to treat cancer, today provided additional data from the company’s ongoing Phase 1/2a SCiStar study designed to evaluate the safety and potential efficacy of AST-OPC1 in the treatment of severe cervical spinal cord injury.   

The SCiStar study is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in 25 subjects with subacute motor complete (AIS-A or AIS-B) cervical (C-4 to C-7) spinal cord injury. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. The SCiStar study consists of five cohorts:

Cohort Injury Type; AST-OPC1 Dose # of Subjects
Cohort 1 AIS-A; 2M AST-OPC1 cells
(low dose for safety evaluation)
3
Cohort 2 AIS-A; 10M AST-OPC1 cells 6
Cohort 3 AIS-A; 20M AST-OPC1 cells* 6
Cohort 4 AIS-B; 10M AST-OPC1 cells 6
Cohort 5 AIS-B; 20M AST-OPC1 cells* 4
Total   25

*One subject from Cohort 3 and one subject from Cohort 5 were administered 10 million cells.

Each subject in Cohorts 3 and 4 has completed a 6 month follow-up and the updated results for the SCiStar study have shown the following:

  • Positive Safety Profile - Asterias has dosed 25 subjects with AST-OPC1 in the SCiStar study and a total of 30 subjects including the five subjects from the previous Phase 1 safety trial who have been followed for as long as seven years.  To date, there have been no serious adverse events (SAEs) related to the AST-OPC1 cells. 
     
  • Cell Engraftment - 92% (11/12) of Cohort 3 and Cohort 4 subjects have magnetic resonance imaging (MRI) scans at six months consistent with the formation of a tissue matrix at the injury site, which is early and encouraging evidence that AST-OPC1 cells have engrafted at the injury site and helped to prevent cavitation.  Together with the previously reported results from Cohort 2, the MRI results-to-date for 94% (17/18) of the Cohort 2-4 subjects provide supportive evidence that AST-OPC1 cells have durably engrafted at the injury site and helped to prevent cavitation.  
     
  • Improved Motor Function - 75% (9/12) of Cohort 3 and Cohort 4 subjects have recovered at least one motor level on at least one side through six months, and 17% (2/12) of subjects have recovered two or more motor levels on at least one side through six months.  At six months, 83% (15/18) of Cohort 2-4 subjects recovered at least 1 motor level on at least one side and 22% (4/18) of Cohort 2-4 subjects recovered two or more motor levels on at least one side.  As previously disclosed, Asterias believes that improved motor function is best evaluated at 12 months post-injection.  More detailed information on improved motor function is provided in table format further below.

“We are pleased to provide this update regarding our ongoing clinical trial of AST-OPC1 for the treatment of severe cervical spinal cord injuries in patients for whom there are no viable treatment options and a high unmet medical need,” stated Michael Mulroy, President and Chief Executive Officer.  “Results-to-date from Cohorts 3 and 4 continue to show a positive safety profile and suggest that AST-OPC1 cells are successfully engrafting in patients, which is consistent with the data from our extensive preclinical testing.    We now have two subjects from Cohorts 3 and 4 who have completed six months of follow-up and recovered two motor levels and nine of the 12 of the subjects in Cohorts 3 and 4 have recovered at least one motor level on at least one side through six months.  The positive safety profile to date, the evidence supporting engraftment of the cells post-implantation, and the improvements we are seeing in upper extremity motor function highlight the promising findings coming from this Phase 1/2a clinical trial, which will guide us as we work to design future studies.  Spinal cord injury is a complex medical disorder that has defied numerous treatment efforts in the past.  With our innovative technological approach to treating this disorder, we are pleased that the results to date from this trial have continued to support further investigation of AST-OPC1.  Because of its novel mechanism of action, AST-OPC1 could also potentially benefit patients with other neurological disorders associated with de-myelination, such as multiple sclerosis and white matter stroke.  Over time, we look forward to studying AST-OPC1 in indications such as these, all of which currently have a high unmet medical need.”

“With the expansion of the number of subjects enrolled in our clinical trial, we are actively analyzing the trial data across a range of factors to determine which patients are best suited for AST-OPC1,” stated Dr. Edward Wirth III, Chief Medical Officer. “In 2018, we will be reviewing the 12-month data from Cohorts 3 and 4 and the six- and 12-month data from Cohort 5 (AIS-B injuries administered 20 million AST-OPC1 cells).  We are looking forward to seeing how the subjects from Cohorts 3-5 progress following their six-month readouts and continuing to learn from the data we collect. With the data we are collecting from the study, we are gaining important insights as to how severity of injury and factors such as post-implantation rehabilitation can potentially influence the recoveries for these patients for whom there are currently no other viable treatment options.”

AST-OPC1 Therapeutic Platform

AST-OPC1, an oligodendrocyte progenitor cell population derived from human embryonic stem cells, has been shown in preclinical testing in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed in demyelination disorders, such as spinal cord injuries, and multiple neurodegenerative diseases, including multiple sclerosis and white matter stroke. These potential reparative functions of AST-OPC1 include the production of neurotrophic factors, the stimulation of vascularization, and the induction of remyelination of denuded axons, all of which are critical for survival and regrowth of—and conduction of nerve impulses through—axons at the injury site.   

Each year in the United States, more than 17,000 people suffer a severe, debilitating spinal cord injury. As of 2016, the National Spinal Cord Injury Statistical Center reported that approximately 4,500 of these new spinal cord injuries annually in the U. S. are AIS-A, AIS-B, or AIS-C patients with C-4 to C-7 spinal cord injuries (https://www.nscisc.uab.edu/). These injuries can be devastating to quality of life and ability to function independently. Lifetime healthcare costs for these patients can often approach $5 million. Improvements in arm, hand, and finger functional capabilities in these patients can result in meaningfully lower healthcare costs, significant improvements in quality of life, greater ability to engage in activities of daily living, and increased independence. 

Together with data from the previously reported Cohort 2 (AIS-A injuries administered 10 million AST-OPC1 cells), updated clinical data from the SCiStar study is set forth in the tables below:

Safety 

Asterias has dosed 25 subjects with AST-OPC1 in the SCiStar study and a total of 30 subjects including the five subjects from the previous Phase 1 safety trial.  The results-to-date, which include subjects from the Phase 1 safety trial who have been followed for as long as seven years, continue to support the safety of AST-OPC1.  In particular, there have been no serious, unexpected, adverse events related to AST-OPC1, the injection procedure, or the drug used for immunosuppression in any of the 30 subjects.  Additionally, long-term follow up in the Phase 1 safety trial with annual MRI scans through five years post-injection of AST-OPC1 has shown no evidence of adverse changes in any of the subjects treated with AST-OPC1.

Magnetic Resonance Imaging (MRI) Data

The MRI results-to-date for 94% (17/18) of the subjects in Cohorts 2, 3, and 4 are consistent with formation of a tissue matrix at the injury site, which is supportive evidence showing that AST-OPC1 cells have durably engrafted at the injury site and helped to prevent cavitation.  Cavitation is a destructive process that occurs within the spinal cord following spinal cord injuries, and typically results in permanent loss of motor and sensory function. Additionally, a patient with cavitation can develop a condition known as syringomyelia, which results in additional neurological and functional damage to the patient.  Published data indicates that about 50% of all subjects with spinal cord injuries develop an injury cavity within six months following the spinal cord injury.  Meanwhile, for subjects with the severe contusive spinal cord injuries that would meet the criteria for inclusion in the SCiStar study, the percentage of subjects that typically develop an injury cavity would be closer to 80%. 

  • All six subjects in Cohort 2 (100%) had serial MRI scans at six months that indicated no sign of lesion cavities in any subject.
  • Five of the six subjects in Cohort 3 (83%) had serial MRI scans at six months that indicated no sign of lesion cavities.  (In the baseline, or pre-injection MRI scan, the one subject with a lesion cavity showed signs of a severe hematoma, or solid swelling of clotted blood, within the spinal cord where the lesion cavity developed.  The MRI scan at six months for this particular subject showed a large fluid-filled lesion cavity at the lesion/injection site where the hematoma had been, which indicates the AST-OPC1 cells did not durably engraft.  This subject is one of the two subjects in Cohort 3 that has seen no motor level recovery as of the subject’s six-month follow-up examination.)
  • All six subjects in Cohort 4 (100%) had serial MRI scans at six months that indicated no sign of lesion cavities in any subject.

Upper Extremity Motor Recovery

Improvements in upper extremity motor function are being measured using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) scale, widely used to quantify functional status of patients with spinal cord injuries. Both patients and physicians consistently report that improvements in upper extremity motor function are the most desirable functional improvement target in the quadriplegic population, since even relatively modest changes can potentially have a significant impact on functional independence, quality of life and cost of care. The SCiStar study is monitoring two separate ISNCSCI measurements of upper extremity motor function. The upper extremity motor score (UEMS), is a scale used to quantify motor function at each of five upper extremity muscle groups driving arm and hand function; these scores are also used to determine "motor levels," which define the level within the cord above which a subject has normal function.  As suggested by existing research, patients with severe spinal cord injuries that show two motor levels of improvement on at least one side may regain the ability to perform daily activities such as feeding, dressing and bathing, which significantly reduces the overall level of daily assistance needed for the patient and associated healthcare costs.

Two-Motor Level Recovery

Cohort Subjects recovering at l
east two motor levels
on at least one side at 6
months
Subjects recovering at
least two motor levels
on at least one side at
12 months
Cohort 2 2/6 4/6
Cohort 3 1/6 TBD
Cohort 4 1/6 TBD
Cohorts 2-4 4/18 TBD

The company’s original tertiary target for the SCiStar study, after observing the safety and activity of AST-OPC1, was that 45-50% of study subjects would recover at least 2 motor levels on at least one side at 12 months, which is approximately double the rate of spontaneous recovery expected based on a similarly matched population and published literature.

One-Motor Level Recovery

Cohort Subjects recovering at
least one motor level on
at least one side at 6
months
Subjects recovering at
least one motor level on
at least one side at 12
months
Cohort 2 6/6 6/6
Cohort 3 4/6 TBD
Cohort 4 5/6 TBD
Cohorts 2-4 15/18 TBD

Upper Extremity Motor Score

Cohort Average UEMS
improvement at 6
months
Average UEMS
improvement at 12
months
Cohort 2 9.7 12.3
Cohort 3 6.0 TBD
Cohort 4 5.5 TBD
Cohorts 2-4 7.1 TBD

Anticipated 2018 Data Readouts for the SCiStar Study

Asterias has completed enrollment and dosing in all five of its planned SCiStar study cohorts.   The company intends to report the following data readouts later this year:

  • 6 month update for the entire SCiStar study, including Cohort 5, late in the second quarter or early third quarter of 2018.
  • 12 month update for Cohorts 3 and 4 in the third quarter of 2018.
  • 24 month update for Cohort 2 in the third or fourth quarter of 2018.
  • 12 month update for the entire SCiStar study, including Cohort 5, late in the fourth quarter of 2018 or early in the first quarter of 2019.

Conference Call and Webcast Today at 5:00 p.m. ET (2:00 p.m. PT) to Discuss the Results

Asterias will host a conference call and webcast today, February 28, 2018 at 5:00 p.m. Eastern / 2:00 p.m. Pacific to discuss the results.

For both "listen-only" participants and those participants who wish to take part in the question-and-answer portion of the call, the dial-in number in the U.S./Canada is 877-723-9523. For international participants outside the U.S./Canada, the dial-in number is 719-457-2605. For all callers, refer to Conference ID 2149071. To access the live webcast, go to http://asteriasbiotherapeutics.com/inv_events_presentations.php.

A replay of the conference call will be available for one month beginning about two hours after the conclusion of the live call, by calling toll-free (from U.S./Canada) 888-203-1112; international callers dial 719-457-0820. Use the Conference ID 2149071. Additionally, the archived webcast will be available at http://asteriasbiotherapeutics.com/inv_events_presentations.php.

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company dedicated to developing cell-based therapeutics to treat neurological conditions associated with de-myelination and cellular immunotherapies to treat cancer. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is an autologous cancer immunotherapy with promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML). AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a first-in-human (FIH) clinical trial of AST-VAC2 in non-small cell lung cancer. Additional information about Asterias can be found at www.asteriasbiotherapeutics.com.    

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor cell population derived from human embryonic stem cells, has been shown in preclinical testing in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed in demyelination disorders, such as spinal cord injuries, and multiple neurodegenerative diseases, including multiple sclerosis and white matter stroke. These potential reparative functions of AST-OPC1 include the production of neurotrophic factors, the stimulation of vascularization, and the induction of remyelination of denuded axons, all of which are critical for survival and regrowth of—and conduction of nerve impulses through—axons at the injury site.   

Each year in the United States, more than 17,000 people suffer a severe, debilitating spinal cord injury. As of 2016, the National Spinal Cord Injury Statistical Center reported that approximately 4,500 of these new spinal cord injuries annually in the U. S. are AIS-A, AIS-B, or AIS-C patients with C-4 to C-7 spinal cord injuries (https://www.nscisc.uab.edu/). These injuries can be devastating to quality of life and ability to function independently. Lifetime healthcare costs for these patients can often approach $5 million. Improvements in arm, hand, and finger functional capabilities in these patients can result in meaningfully lower healthcare costs, significant improvements in quality of life, greater ability to engage in activities of daily living, and increased independence. 

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in 25 subjects with subacute motor complete (AIS-A or AIS-B) cervical (C-4 to C-7) SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A subjects have lost all motor and sensory function below their injury site, while AIS-B subjects have lost all motor function but may have retained some minimal sensory function below their injury site. AST-OPC1 is administered 21 to 42 days post-injury. Subjects will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.

Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Additional information on the Phase 1/2a trial, including trial sites, can be found at www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com). 

SOURCE: Asterias Biotherapeutics

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