SL1009 targets a 2025 FDA decision for Pyruvate Dehydrogenase Complex Deficiency (PDCD), while SL1002 advances toward Phase III trials for osteoarthritis knee pain and spasticity

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, April 17, 2025 /PRNewswire/ -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, today announced multiple updates on its rapidly advancing clinical development portfolio.

SL1009, Sodium Dichloroacetate (DCA)

DCA is an investigational product, that if approved, will be used with a proprietary dose-related genetic test to treat an orphan pediatric mitochondrial disease, Pyruvate Dehydrogenase Complex Deficiency (PDCD).  PDCD is a rare and life-threatening genetic disorder that causes chronic energy deficit leading to lactic acidosis, profound developmental problems and early childhood death.

DCA has received Fast Track Designation, Orphan Drug Designation, and Rare Pediatric Disease Designation, making it eligible for Priority Review and a Priority Review Voucher. The FDA recently notified Saol of a 90-day extension to the NDA review, moving the PDUFA date from May 27, 2025, to August 27, 2025.  No concerns were raised by the FDA about the adequacy of the filing or the need for an advisory committee meeting.  Saol, in collaboration with Medosome Biotec, also filed the Humanitarian Device Exemption (HDE) application for the dose-related genetic test that will serve as a required companion diagnostic for patients treated with DCA.

“We are working with the FDA to secure approval for this product this year,” said Dave Penake, CEO. “Our entire organization is united in the mission to bring hope to patients and families who have been waiting for this breakthrough therapy.”

For PDCD patients who did not participate in the clinical trial, Saol is now advancing an expanded access program (EAP).  More information can be found at Clinicaltrials.gov, NCT06931262.

Further, Saol is preparing for a Type C meeting with the FDA to discuss the clinical development program for the use of DCA in the treatment of congenital lactic acidosis (CLA). Congenital lactic acidosis is caused by inborn errors of metabolism, including PDCD, often presenting early in life, leading to lactic acid accumulation, with high mortality.

SL1002

SL1002 is an investigational, novel perineural chemoneurolytic injection that utilizes Saol’s proprietary CYCLOPHLEX™ technology.  It is currently being advanced in development for the treatment of chronic knee pain related to osteoarthritis and for limb spasticity, both in the adult population (18+).

“SL1002 continues to be a program with enormous potential,” said Penake. “Our recent FDA End of Phase II meeting provided a clear regulatory path for our osteoarthritis pain program. We are eager to initiate our pivotal program this year. Meanwhile, our spasticity data was recently presented by our investigators and received positive feedback from thought leaders in the field. As we further explore SL1002’s therapeutic potential, it is becoming increasingly clear that this program has far-reaching possibilities to treat patients with a variety of neuromuscular disorders.”

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland, and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

Saol Therapeutics Contact

Senior Vice President, Strategy

Brian Nappi

bnappi@saolrx.com

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, January 28, 2025 – Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for SL1009, Sodium Dichloroacetate Oral Solution (DCA).  DCA will be used with a proprietary genetic test to treat an orphan pediatric mitochondrial disease, Pyruvate Dehydrogenase Complex Deficiency (PDCD)¹. The FDA granted Priority Review for the NDA and has set a goal date of May 27, 2025, under the Prescription Drug User Fee Act (PDUFA). Priority review is designated to applications for drugs that, if approved, would provide a significant improvement in safety or effectiveness of the treatment, prevention or diagnosis of a serious medical condition. SL1009 has previously been granted Orphan Drug and Fast Track Designations. SL1009 has also been granted a Rare Pediatric Disease Designation by the FDA and thus is eligible for a Priority Review Voucher (PRV).

PDCD is a rare and life-threatening mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure. DCA is a targeted therapy that inhibits Pyruvate Dehydrogenase Kinase (PDK) to stimulate residual Pyruvate Dehydrogenase Complex (PDC) activity and increase energy (ATP) production by mitochondria.

"This NDA acceptance brings us one step closer to addressing the critical health challenges faced by these children and their families, where no approved treatment is currently available," said Dave Penake, Chief Executive Officer of Saol Therapeutics. “Reaching this regulatory milestone is both a significant scientific achievement and a deeply meaningful moment for everyone who has dedicated themselves to advancing this therapy. Further, designating our application for priority review reaffirms that the FDA views PDCD as a serious condition”

The NDA is supported by results from a Phase 3 double-blind placebo-controlled cross-over study (SL1009-01) and a survival study (SL1009-02). The totality of evidence submitted for review in the NDA includes mechanistic characterization, along with nonclinical and clinical evidence to demonstrate the safety and clinical benefit of DCA in PDCD patients.

DCA is not currently approved for any indication in the United States.

About Pyruvate Dehydrogenase Complex Deficiency (PDCD)

PDCD is a mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure.  It is estimated that 300-500 patients are treated in expert centers in the US, and the overall prevalence is thought to be as high as 2,000.  PDCD is the most common cause of congenital lactic acidosis, a life-threatening condition that may occur as early as the neonatal period. Patients suffering from PDCD may also exhibit extreme tiredness (lethargy), poor feeding, rapid breathing (tachypnea), and other signs of neurological and neuromuscular dysfunction such as developmental delay, low muscle tone (hypotonia), abnormal eye movements and seizures. Signs and symptoms usually begin soon after birth but may appear later in childhood².

There are currently no FDA-approved therapies for PDCD.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

Saol Therapeutics Contact
Brian Nappi, Senior Vice President, Strategy
bnappi@saolrx.com

References

1. 1. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=45290, Accessed January 2025
2. 2. Ganetzky R, McCormick EM, Falk MJ. Primary Pyruvate Dehydrogenase Complex Deficiency Overview. 2021 Jun 17. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. PMID: 34138529.

ROSWELL, Ga. and DUBLIN and HAMILTON, Bermuda, Dec. 3, 2024 /PRNewswire/ -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for approval of SL1009, Sodium Dichloroacetate Oral Solution (DCA) for use with a proprietary genetic test, for the treatment of an orphan pediatric mitochondrial disease, Pyruvate Dehydrogenase Complex Deficiency (PDCD)¹. SL1009 has been granted Orphan Drug, Fast Track and Rare Pediatric Disease Designations by the FDA and is thus eligible for Priority Review and a Priority Review Voucher.

The NDA is supported by results from the Phase 3 double-blind placebo controlled cross-over study (SL1009-01) and a survival study (SL1009-02). The totality of evidence submitted in the NDA includes mechanistic characterization, nonclinical and clinical safety and efficacy evidence to support the clinical benefit of DCA in PDCD patients.

The primary endpoint of SL1009-01 was a daily Observer Reported Outcomes survey tool to measure changes in motor domains (ObsRO_motor) as well as the safety and tolerability of SL1009 compared to placebo. A key secondary endpoint measured the reduction in plasma lactate of SL1009 compared to placebo. Patients receiving DCA were dose-stratified post-randomization utilizing a proprietary genetic test. The test identifies each patient's GSTZ1 genotype to provide individualized dosing intended to reduce adverse events, such as peripheral neuropathy.

A second study, SL1009-02, was a survival analysis that compared outcomes for DCA-treated patients in the Phase III study with external, untreated natural history cohort of patients with PDCD. Patients were matched on age and sex.

Peter Stacpoole, MD, initial study sponsor of SL1009-01 said "The NDA submission is a tremendous milestone and the culmination of years of effort. I am grateful for the clinicians and families who participated in the trial."

Detailed data is expected to be presented at an upcoming medical conference.

DCA is not currently approved for any indication in the United States.

About SL1009 (DCA) and GSTZ1/MAAI Proprietary Genetic Test 

SL1009, if approved by the FDA after a review of safety and efficacy, has the potential to be the 1^st approved medication for the mitochondrial disease PDCD and would be available as an oral solution. Gene mutations in the mitochondrial Pyruvate Dehydrogenase Complex (PDC) lead to congenital PDCD. PDC is inhibited by pyruvate dehydrogenase kinases (PDK), that may be over-expressed in PDCD. DCA inhibits PDK to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. Dosing is based on a proprietary genetic test that dichotomizes subjects into "fast" and "slow" drug metabolizers, providing individualized dosing.

About Pyruvate Dehydrogenase Complex Deficiency (PDCD)

PDCD is a mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure. It is estimated that 300-500 patients are treated in expert centers in the US, and the overall prevalence is thought to be as high as 2,000. PDCD is the most common cause of congenital lactic acidosis, a life-threatening condition that may occur as early as the neonatal period. Patients suffering from PDCD may also exhibit extreme tiredness (lethargy), poor feeding, rapid breathing (tachypnea), and other signs of neurological and neuromuscular dysfunction such as developmental delay, low muscle tone (hypotonia), abnormal eye movements and seizures. Signs and symptoms usually begin soon after birth but may appear later in childhood².

There are currently no FDA-approved therapies for PDCD.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit www.saolrx.com.

References

1. 1. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=45290, Accessed October 2024
2. 2. Ganetzky R, McCormick EM, Falk MJ. Primary Pyruvate Dehydrogenase Complex Deficiency Overview. 2021 Jun 17. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. PMID: 34138529.

Saol Therapeutics Contact
Senior Vice President, Strategy
Brian Nappi
bnappi@saolrx.com

SL-1002 demonstrated a favorable safety profile in adult patients with limb spasticity, achieving the primary safety endpoint of this first-in-human study. Key secondary efficacy endpoints were also met, including a statistically significant reduction in the Modified Ashworth Score at 6 months.

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, October 30, 2024 /PRNewswire/ -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, today announced positive topline results from its SL-1002 RAISE Limb Spasticity Trial (NCT05311215).  The data were recently presented at the Spasticity X Symposium in Houston, Texas.

Dr. Sheng Li, MD, PhD, Professor in the the Department of Physical Medicine and Rehabilitation (PM&R) at McGovern Medical School at UTHealth Houston and Director of Stroke Rehabilitation and Recovery Research at TIRR Memorial Hermann Hospital, along with Dr. Gerard Francisco, MD, professor and The Wulfe Family Chair of Physical Medicine and Rehabilitation at McGovern Medical School at UTHealth Houston and Chief Medical Officer at TIRR Memorial Hermann, presented the findings.

SL-1002 is a novel chemoneurolytic injection utilizing Saol’s proprietary CYCLOPHLEX™ technology. In the RAISE Limb Spasticity Trial, patients were randomized (3:1) into a double-blind, vehicle-controlled, single-ascending-dose escalation study designed to assess the safety and efficacy of a single SL-1002 treatment in patients with mild to severe limb spasticity. The study period lasted 26 weeks post-randomization, and the primary endpoint was to evaluate the overall safety profile of SL-1002 compared to vehicle.

A total of 32 patients were randomized in the trial (24 receiving SL-1002, 8 receiving vehicle). Five serious adverse events (SAEs) were reported, all determined by investigators to be unrelated to the treatment. Fourteen non-serious treatment-emergent adverse events (TEAEs) determined by the investigators to be possibly, probably, or definitely related to treatment were observed, all were considered mild. There were other mild and moderate non-serious treatment-emergent adverse events (TEAEs) considered by the investigators to be unrelated to the treatment. Overall, SL-1002 was deemed well-tolerated, with no therapy- or program-limiting adverse events.

Key secondary endpoints included assessments using the Modified Ashworth Scale (MAS), the most widely used efficacy measurement in spasticity trials. Despite the trial not being powered for efficacy, SL-1002 demonstrated a statistically significant improvement over vehicle at multiple time points throughout the trial.  At 6 months, the SL-1002 arm showed a statistically significant reduction in MAS compared to baseline, with a decrease of -1.18, compared to -0.33 reduction in the vehicle arm (p=0.0060).

"We are thrilled to share the positive results from the RAISE Limb Spasticity Trial," said Dave Penake, CEO of Saol Therapeutics. "Spasticity can be an incredibly debilitating condition, and the need for new treatment options has been voiced by patients and clinicians. We are especially encouraged by the strong safety profile observed in the RAISE study, alongside the efficacy shown by SL-1002 lasting at least 6 months. Achieving a 1–2-point reduction in MAS is a significant, positive, clinical outcome, and the durability of the treatment give us great confidence in the future of this program."

Penake added, "None of this would have been possible without the patients who volunteered for this study and the dedicated investigators and clinical trial site teams. Their collaboration and commitment are what drive medical progress, and we are deeply grateful for their contributions."

Dr. Gerard Francisco, the Principal Investigator for the trial, commented, "Treating spasticity is complex, and there is an urgent need for more innovative therapies. These early results show that SL-1002 appears to be safe, effective, and durable. "

The RAISE Limb Spasticity Trial was conducted at UTHealth Houston in Houston, TX, where Dr. Sheng Li and Dr. Gerard Francisco served as the investigators, and at the Medical College of Wisconsin in Milwaukee, WI, where Dr. John McGuire served as the Principal Investigator.

Saol Therapeutics plans to meet with the FDA in the first half of 2025 to determine the next steps in the SL-1002 spasticity program.  SL-1002 is also being investigated for the treatment of pain related to osteoarthritis of the knee in the COMPASS Osteoarthritis Knee Pain Trial, with results yet to be released.

About RAISE Limb Spasticity Trial

The RAISE Limb Spasticity trial is a Randomized double-blind, vehicle-controlled, single AscendIng dose escalation study to assess the Safety, Pharmacokinetics and Efficacy of SL-1002 in adult patients with limb spasticity.  (NCT05311215).

About COMPASS Osteoarthritis Knee Pain Trial

In addition to the RAISE Spasticity Trial, SL-1002 is also being investigated for the treatment of pain related to osteoarthritis of the knee.  The COMPASS Osteoarthritis Knee Pain Trial is a multicenter, randomized, double-blind, vehicle-COntrolled, single-ascending dose escalation study to assess the safety and efficacy of SL-1002 injectable for treatMent of PAin aSSociated with OsteoArthritis of the knee.  (NCT05470608).

About SL-1002

SL-1002 is a novel, chemoneurolytic injection, that utilizes Saol’s proprietary CYCLOPHLEX^TM technology. It is currently being developed for the treatment of chronic knee pain related to osteoarthritis and limb spasticity, both in the adult population (18+) in the United States.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland, and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

Saol Therapeutics Contact

Senior Vice President, Strategy

Brian Nappi

bnappi@saolrx.com

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, October 22, 2024 / -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today that topline safety and efficacy data for the SL-1002 RAISE Limb Spasticity Trial (NCT05311215) will be presented at the Spasticity X Symposium in Houston, TX on October 25, 2024.

Presentation Title: Results of the Phase II Study of SL-1002 in Limb Spasticity
Presentation Date and Time: Friday, October 25, from 4:10-4:30pm CST
Presenters:

Sheng Li, MD, PhD, Houston, TX 

• Professor, Department of Physical Medicine and Rehabilitation (PM&R) at McGovern Medical School at UTHealth
• Attending Physician, TIRR Memorial Herman
• Director, Stroke Rehabilitation and Recovery Research, TIRR Memorial Hermann Hospital
• Director, Neurorehabilitation Research Laboratory and UTHealth NeuroRecovery Research Center at TIRR Memorial Hermann

Gerard Francisco, MD, Houston, TX 

• The Wulfe Family Chair Of Physical Medicine And Rehabilitation, McGovern Medical School - UTHealth
• Chairman And Professor (With Tenure), Distinguished Teaching Professor, UT Systems
• Chief Medical Officer And Clinical Scientist, TIRR Memorial Hermann

“We are very pleased to have the SL-1002 RAISE Limb Spasticity Trial topline data presented at Spasticity X,” said Saol Therapeutics CEO Dave Penake.  “This symposium will bring together some of the world’s leading experts in spasticity management, and we’re excited to share the progress of our SL-1002 program with them in Houston.”

SL-1002 is a novel, chemoneurolytic injection, that utilizes Saol’s proprietary CYCLOPHLEX^TM technology.

The RAISE Limb Spasticity Trial is a randomized (3:1), double-blind, vehicle-controlled single ascending dose escalation study intended to assess the safety, pharmacokinetics, and efficacy of a single treatment of SL-1002 in patients with mild to severe limb spasticity. Following randomization, the study period lasted 26 weeks.  The primary endpoint is the overall safety profile of a single treatment exposure of SL-1002 in comparison to vehicle.

About RAISE Limb Spasticity Trial

The RAISE Limb Spasticity Trial is a Randomized double-blind, vehicle-controlled, single AscendIng dose escalation study to assess the Safety, Pharmacokinetics and Efficacy of SL-1002 in adult patients with limb spasticity.  (NCT05311215).

About COMPASS Osteoarthritis Knee Pain Trial

In addition to the RAISE Spasticity Trial, SL-1002 is also being investigated for the treatment of pain related to osteoarthritis of the knee.  The COMPASS Osteoarthritis Knee Pain Trial is a multicenter, randomized, double-blind, vehicle-COntrolled, single-ascending dose escalation study to assess the safety and efficacy of SL-1002 injectable for treatMent of PAin aSSociated with OsteoArthritis of the knee.  (NCT05470608).

About SL-1002

SL-1002 is a novel, chemoneurolytic injection, that utilizes Saol’s proprietary CYCLOPHLEX^TM technology. It is currently being developed for the treatment of chronic knee pain related to osteoarthritis and limb spasticity, both in the adult population (18+) in the United States.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland, and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

Entrepreneur Of The Year celebrates ambitious entrepreneurs who are shaping the future

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, May 1, 2024– Ernst & Young LLP (EY US) today announced that CEO Dave Penake of Saol Therapeutics was named an Entrepreneur Of The Year^® 2024 Southeast Award finalist. The Southeast program celebrates entrepreneurs from Alabama, Georgia, North Carolina, South Carolina and Tennessee.  Now in its 38th year, Entrepreneur Of The Year is the preeminent competitive business award for audacious leaders who disrupt markets, revolutionize sectors and have a transformational impact on lives. Over the past four decades, the program has recognized the daring entrepreneurs with big ideas and bold actions that reshape our world.

Penake was one of 34 regional entrepreneurs selected as finalists by an independent panel of judges. The candidates were evaluated based on their demonstration of building long-term value through entrepreneurial spirit, purpose, growth and impact, among other core contributions and attributes.

“It’s a tremendous honor to be recognized by EY as an Entrepreneur Of The Year^® Southeast Award finalist,” said Penake.  “Our team at Saol is so passionate about our work.  Every day, we try to make a difference and find ways to help more patients.  This recognition is a wonderful reflection of what we have accomplished to date as a team at Saol Therapeutics.”

Penake has been the CEO of Saol Therapeutics since 2016.  His leadership has shaped the company's trajectory, including securing over $100M in financing and orchestrating divestitures that provide funding for advancing new product development.

Under his guidance, Saol's late-stage pipeline continues to progress rapidly.  The company recently announced the completion of enrollment in a Phase III trial for a rare mitochondrial disease – Pyruvate Dehydrogenase Complex Deficiency (PDCD).  This program has received Orphan, Rare Pediatric, and Fast Track Designation from the FDA.

Separately, Saol has also completed enrollment in two separate Phase II studies for the company's SL-1002 program, which is currently being studied for both the treatment of spasticity and pain related to knee osteoarthritis.

“As exciting as the last few years have been at Saol, I believe we are still just in the early stages of what we are ultimately going to accomplish as we continue to grow this company,” added Penake.  “We have made significant strides in progressing all three of our development programs recently, and I continue to see the team looking for ways to accelerate our progress.  Every employee at Saol is truly an entrepreneur at their core, and it’s one of the reasons I think we all enjoy what we are building here together.”

Entrepreneur Of The Year honors many different types of business leaders for their ingenuity, courage and entrepreneurial spirit. The program celebrates original founders who bootstrapped their business from inception or who raised outside capital to grow their company; transformational CEOs who infused innovation into an existing organization to catapult its trajectory; and multigenerational family business leaders who reimagined a legacy business model to fortify it for the future.

Regional award winners will be announced on June 20 during a special celebration and will become lifetime members of an esteemed community of Entrepreneur Of The Year alumni from around the world. The winners will then be considered by the National judges for the Entrepreneur Of The Year National Awards, which will be presented in November at the annual Strategic Growth Forum^®, one of the nation’s most prestigious gatherings of high-growth, market-leading companies.

In addition to Entrepreneur Of The Year, EY US supports other entrepreneurs through the EY Entrepreneurial Winning Women™ program and the EY Entrepreneurs Access Network to help connect women founders and Black and Hispanic/Latino entrepreneurs, respectively, with the resources, network and access needed to unlock their full potential.

Sponsors

Founded and produced by Ernst & Young LLP, the Entrepreneur Of The Year Awards include presenting sponsors PNC Bank, Cresa, Marsh USA, SAP and the Ewing Marion Kauffman Foundation. In In the Southeast, sponsors also include VACO LLC as the regional Platinum sponsor; King & Spalding as the regional Gold sponsor; and ADP and Babbit Bodner as the regional Silver sponsors.

About Entrepreneur Of The Year^®

Founded in 1986, Entrepreneur Of The Year^® has celebrated more than 11,000 ambitious visionaries who are leading successful, dynamic businesses in the US, and it has since expanded to nearly 80 countries and territories globally.

The US program consists of 17 regional programs whose panels of independent judges select the regional award winners every June. Those winners compete for national recognition at the Strategic Growth Forum^® in November where National finalists and award winners are announced. The overall National winner represents the US at the World Entrepreneur Of The Year^® competition. Visit ey.com/us/eoy.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

About EY

EY exists to build a better working world, helping to create long-term value for clients, people and society and build trust in the capital markets.

Enabled by data and technology, diverse EY teams in over 150 countries provide trust through assurance and help clients grow, transform and operate.

Working across assurance, consulting, law, strategy, tax and transactions, EY teams ask better questions to find new answers for the complex issues facing our world today.

EY refers to the global organization, and may refer to one or more, of the member firms of Ernst & Young Global Limited, each of which is a separate legal entity. Ernst & Young Global Limited, a UK company limited by guarantee, does not provide services to clients. Information about how EY collects and uses personal data and a description of the rights individuals have under data protection legislation are available via ey.com/privacy. EY member firms do not practice law where prohibited by local laws. For more information about our organization, please visit ey.com.

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, February 12, 2024 – Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today that the FDA has granted Fast Track Designation for Dichloroacetate (DCA, SL-1009) for the treatment of an orphan pediatric mitochondrial disease, Pyruvate Dehydrogenase Complex Deficiency (PDCD)¹.

Fast Track designation is granted to expedite the development and review of drugs that treat serious conditions and fill an unmet medical need. DCA (SL-1009) has demonstrated potential to address such needs in PDCD^2,3.  Fast Track accelerates the availability of promising therapies to patients in need.

"We are pleased to receive Fast Track Designation from the FDA for SL-1009 for the treatment of PDCD," said Dave Penake, CEO of Saol Therapeutics. "This designation allows for submission of the NDA as Rolling Review. DCA (SL-1009) already has Orphan Drug Designation, as well as Rare Pediatric Disease Designation and is thus eligible for Priority Review and a Priority Review Voucher. We are hoping to file our NDA in 2024.   PDCD is a debilitating progressive disease⁴.  Such designations provide expedited pathways to enable us to bring this much-needed therapy to patients more swiftly."

"PDCD is a devastating childhood disease, characterized by progressive neurological and neuromuscular deterioration, lactic acidosis and early death⁴. Receiving Fast Track designation from the FDA is a testament to the dedication and collaborative efforts of our colleagues over many years and underscores the urgency and potential impact of our work in PDCD” notes Dr. Peter W. Stacpoole, Professor of Medicine at the University of Florida and Principal Investigator of the DCA/PDCD trial.  “We hope our DCA (SL-1009) NDA will be reviewed expeditiously and, when approved, will bring this drug to the children and families who have been long-waiting for an effective therapy.”

About the Phase 3 Clinical Trial

This trial evaluated daily administration of DCA in children with a confirmed pathological mutation in the Pyruvate Dehydrogenase Complex. The primary efficacy outcome measure was based on a novel Observer Reported Outcome (ObsRO) survey developed specifically for this trial.

The study design was a 9-month double-blind crossover comparison between DCA and placebo, during which the ObsRO is completed daily by a parent/caregiver, followed by an open-label phase of DCA administration.   The last patient completed the double-blind portion of the trial in August of 2023.  The majority of participants are currently in the open-label phase. More information on the clinical trial and participating institutions can be found at Phase 3 PDCD Trial (NCT02616484).

About DCA (SL-1009) 

DCA, if approved by the FDA after a review of safety and efficacy, has the potential to be the 1^st approved medication for the mitochondrial disease PDCD and would be available as an oral solution.  Gene mutations in the mitochondrial Pyruvate Dehydrogenase Complex (PDC) lead to congenital PDCD. PDC is inhibited by pyruvate dehydrogenase kinases (PDK), that may be over-expressed in PDCD. DCA inhibits PDK to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. Dosing is based on a proprietary genetic test that dichotomizes subjects into “fast” and “slow” drug metabolizers, providing individualized dosing.

About Pyruvate Dehydrogenase Complex Deficiency (PDCD)

PDCD is a mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure.  It affects several hundred individuals in the U.S.  It is a common cause of congenital lactic acidosis, a life-threatening condition that may occur as early as the neonatal period. Patients may also exhibit extreme tiredness (lethargy), poor feeding, rapid breathing (tachypnea), and other signs of neurological and neuromuscular dysfunction such as developmental delay, low muscle tone (hypotonia), abnormal eye movements and seizures. Signs and symptoms usually begin soon after birth but may appear later in childhood⁴.

There are currently no FDA-approved therapies for PDCD.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

References

1. 1. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=45290, Accessed February 2024
2. 2. Stacpoole PW, Gilbert LR, Neiberger RE, Carney PR, Valenstein E, Theriaque DW, Shuster JJ. Evaluation of long-term treatment of children with congenital lactic acidosis with dichloroacetate. Pediatrics. 2008 May;121(5):e1223-8. doi: 10.1542/peds.2007-2062. Epub 2008 Apr 14. PMID: 18411236; PMCID: PMC3777225.
3. 3. Stacpoole PW, Kerr DS, Barnes C, Bunch ST, Carney PR, Fennell EM et al. Controlled Clinical Trial of Dichloroacetate for Treatment of Congenital Lactic Acidosis in Children. Pediatrics. 17(5);1519-1531, 2006.
4. 4. Ganetzky R, McCormick EM, Falk MJ. Primary Pyruvate Dehydrogenase Complex Deficiency Overview. 2021 Jun 17. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. PMID: 34138529.

SL-1002 is currently being developed for the treatment of chronic knee pain associated with osteoarthritis (COMPASS Trial) and mild to severe limb spasticity (RAISE Trial). Topline data for the COMPASS Osteoarthritis Knee Pain Trial will be available in the first quarter of 2024, with topline data from the RAISE Limb Spasticity Trial available shortly thereafter. 

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, September 19, 2023 / PRNewswire/ – Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today that enrollment has been completed in the company’s two Phase II trials for SL-1002.

Both the COMPASS Osteoarthritis Knee Pain Trial (NCT05470608) and the RAISE Limb Spasticity Trial (NCT05311215) are each fully enrolled, at 132 patients and 32 patients, respectively.

SL-1002 is a novel, chemoneurolytic injection, that utilizes Saol’s proprietary CYCLOPHLEX^TM technology.

“Running parallel, multi-indication Phase II studies for SL-1002 has only been possible due to our committed investigator partners, their research teams, and the tireless work of the employees at Saol Therapeutics,” said David Penake, CEO of Saol Therapeutics.   “This is a tremendous milestone for our company, and we look forward to sharing the results with the medical community.  While celebrating this accomplishment, our team has already shifted into preparing for what will be necessary to initiate the Phase III programs and expansion to other important indications.”

The COMPASS Osteoarthritis Knee Pain Trial is a multicenter, randomized (3:1), double-blind, placebo-controlled, single ascending-dose escalation study to assess the safety and efficacy of SL-1002 for the treatment of chronic knee pain associated with osteoarthritis in adult patients.  The efficacy of SL-1002 will be assessed in comparison to placebo in its ability to reduce the average pain intensity at 3 months (12 weeks). The safety of SL-1002 will be assessed throughout the study compared to placebo when used for treating chronic knee pain associated with osteoarthritis.  Additional secondary measures include improvements in function, concomitant medication, and healthcare utilization.

“The completion of enrollment in the COMPASS Osteoarthritis Knee Pain Trial brings this therapy one step closer to ultimately helping patients,” said Principal Investigator Zachary McCormick, MD, Vice Chair and Associate Professor of Physical Medicine and Rehabilitation at the University of Utah.  “Recent developments in our understanding of the neuroanatomy of the knee indicate that this treatment could be incredibly beneficial to the millions of patients who deal with chronic pain related to osteoarthritis of the knee.  We have enjoyed collaborating with the Saol Therapeutics team and the 14 additional sites in the COMPASS trial. I look forward to seeing the results soon.”

The RAISE Limb Spasticity Trial is a randomized (3:1), double-blind, placebo-controlled single ascending dose escalation study intended to assess the safety, pharmacokinetics, and efficacy of a single treatment of SL-1002 in patients with mild to severe limb spasticity. Following randomization, the study period will be up to 26 weeks.  The primary endpoint is the overall safety profile of a single treatment exposure of SL-1002 in comparison to a placebo.

Saol Therapeutics currently expects topline results for the COMPASS Osteoarthritis Knee Pain Trial in the first quarter of 2024, and the RAISE Limb Spasticity Trial in the second quarter of 2024.

About COMPASS Osteoarthritis Knee Pain Trial

The COMPASS Osteoarthritis Knee Pain Trial is a multicenter, randomized, double-blind, placebo-COntrolled, single-ascending dose escalation study to assess the safety and efficacy of SL-1002 injectable for treatMent of PAin aSSociated with OsteoArthritis of the knee.  (NCT05470608).

About RAISE Limb Spasticity Trial

The RAISE Limb Spasticity trial is a Randomized double-blind, placebo-controlled, single AscendIng dose escalation study to assess the Safety, Pharmacokinetics and Efficacy of SL-1002 in adult patients with limb spasticity.  (NCT05311215).

About SL-1002

SL-1002 is a novel, chemoneurolytic injection, that utilizes Saol’s proprietary CYCLOPHLEX^TM technology. It is currently being developed for the treatment of chronic knee pain related to osteoarthritis and limb spasticity, both in the adult population (18+) in the United States.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland, and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

Saol Therapeutics Contact

Senior Vice President, Strategy
Brian Nappi
bnappi@saolrx.com

The third cohort of the COMPASS trial confirmed the highest planned dose target for the study is well tolerated. 

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, April 12, 2023 / – Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today the company’s Phase II COMPASS Trial is moving into the fourth and final cohort, where it will enroll approximately 100 patients. 

SL-1002 is a novel, proprietary chemoneurolytic injection currently under development at Saol Therapeutics and is being evaluated in the COMPASS Osteoarthritis Knee Pain Trial. The trial is a multicenter, randomized, double-blind, placebo-controlled, single ascending-dose escalation study to assess the safety and efficacy of SL-1002 for the treatment of knee pain associated with osteoarthritis in adult patients (NCT05470608). 

“We are pleased that the Safety and Dose Escalation Committee (SDEC) continues to confirm that there have been no dose limiting adverse events in cohorts 1, 2 or 3. Saol will be advancing the COMPASS trial into the 4th and largest cohort to establish efficacy,” said Saol Therapeutics CEO David Penake. 

In addition to the COMPASS Osteoarthritis Knee Pain Trial, Saol Therapeutics is also sponsoring the RAISE Spasticity Trial (NCT05311215), evaluating the safety, pharmacokinetics and efficacy profile of SL-1002 in adult patients with limb spasticity. Enrollment has also advanced through completion of the third patient cohort. 

“SL-1002 continues to be an exciting program for our company and we are encouraged with the progress to date,” added Penake. “We want to thank the patients and clinicians for their partnership in our Phase II program.” 

Saol Therapeutics currently expects topline results of both the COMPASS Osteoarthritis Knee Pain Trial and the RAISE Spasticity Trial to readout by early 2024. 

About COMPASS Osteoarthritis Knee Pain Trial 

The COMPASS Osteoarthritis Knee Pain Trial is a multicenter, randomized, double-blind, placebo-COntrolled, single-ascending dose escalation study to assess the safety and efficacy of SL-1002 injectable for treatMent of PAin aSSociated with OsteoArthritis of the knee. 

Saol began enrolling patients in the COMPASS Osteoarthritis Pain Trial in the 3rd Quarter of 2022. (NCT05470608). 

About RAISE Spasticity Trial 

The RAISE Spasticity trial is a Randomized double-blind, placebo-controlled, single AscendIng dose escalation study to assess the Safety, Pharmacokinetics and Efficacy of SL-1002 in adult patients with limb spasticity. (NCT05311215). 

About SL-1002 

SL-1002 is a novel, proprietary chemoneurolytic injection currently under investigation for the treatment of limb spasticity and pain related to osteoarthritis of the knee in adults. 

About Saol Therapeutics 

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit www.saolrx.com. 

• By signing an agreement with Medosome Biotec
• By providing support for clinical trial treatment of GBM at the University of Florida
• By starting a collaborative research project in rare pediatric cancers with a leading cancer center

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, March 15, 2023 / PRNewswire/ –

Saol Therapeutics (“Saol”), a privately held, clinical-stage pharmaceutical company, announced today the signing of an agreement with Medosome Biotec to provide Saol the rights to use their patented genotype test for all potential indications where SL-1009 might be used as a therapy.   The test is performed to identify potential mutations at GSTZ1 (glutathione S-transferase zeta 1 human enzyme) that categorize individuals as fast or slow metabolizers of DCA (SL-1009).   Utilization of the genotype testing enables individual dosing, potentially reducing the incidence of treatment related adverse events.  Prior to this agreement Saol only had rights to the patented genotype test for the indication of Pyruvate Dehydrogenase Complex Deficiency (PDCD).

As part of the agreement Saol will aid patient recruitment efforts for the Phase IIA Trial of DCA in Glioblastoma Multiforme (GBM) by providing additional funding and resource support.  Glioblastoma is aggressive and the most common type of primary brain cancer in adults.  GBM is difficult to treat and there is no known cure.  This study, sponsored by the University of Florida and the Food and Drug Administration (FDA) (NCT05120284), is further supported in partnership with Medosome Biotec and Saol.

Dr. Peter Stacpoole is Principal Investigator for the PDCD trial and the GBM trial and is Professor of Medicine at University of Florida. Dr. Stacpoole stated, “We are pleased to expand our partnership with Saol Therapeutics.  Our partnership has led to over-enrollment of our Phase III study in PDCD (NCT02616484) and we mutually see the broader potential application of DCA as the prototypic inhibitor of Pyruvate Dehydrogenase Kinases (PDKs) that, in turn, inhibit PDC enzymatic activity. We look forward to collaborating with Saol on potential additional indications for DCA.  Expansion of our collaboration on the GBM trial will result in the addition of more study sites, allowing for quicker recruitment of patients.  We are hopeful that DCA will be an important addition to the treatment of GBM.”

Saol also recently signed a sponsored research agreement with a leading cancer center to evaluate DCA in rare pediatric solid tumors.  The preclinical research will investigate DCA alone and in combination with chemotherapy in several different pediatric tumor models, such as Wilms, Neuroblastoma, Rhabdoid Tumor, Osteosarcoma, Ewing Sarcoma, and Rhabdomyosarcoma.

Literature suggests that DCA could be effective in several rare, pediatric, solid tumors.  The rationale for the pediatric tumor screening includes the fact that DCA has been widely studied in animals and humans and has a mechanism of action that might override the Warburg effect seen in cancer cells^1,2,3,4.  Saol is currently studying this medicine in children using a proprietary formulation developed for pediatric use (NCT02616484).  “If the pre-clinical assessment provides encouraging data, the work already in pediatric patients may allow us to quickly transition toward clinical investigation”, commented Dr. Virinder Nohria, Chairman and Chief Medical Officer at Saol.

These agreements, and the additional investments behind them, represent an important next step in the evolution of Saol Therapeutics as an emerging pharmaceutical company.  “Now that we have completed enrollment in the PDCD trial we are rapidly transitioning to other important therapeutic areas, and are evaluating the utility of DCA (SL-1009) in adult and pediatric oncology indications with limited treatment options”, said Saol CEO David Penake. “We are pleased to have executed these agreements to support our pursuit of expanded opportunities beyond PDCD”.

Saol expects to have topline data in the PDCD trial in the 3^rd quarter of 2023. Should the results of the trial support a subsequent FDA approval, it will be the first and only medicine approved for this rare, pediatric indication.

References

1. 1. Aminzadeh S, Vidali S, Sperl W, Kofler B, Feichtinger RG. Energy metabolism in neuroblastoma and Wilms tumor. Transl Pediatr. 2015 Jan;4(1):20-32. doi: 10.3978/j.issn.2224-4336.2015.01.04.
2. 2. Guo JQ, Tang HY, Wang CD, Sang BT, Liu X, Yi FP, Liu GL, Wu XM. Influence of Dichloroacetate on Wilms' Tumor in vitro. Ann Clin Lab Sci. 2022 Jan;52(1):101-108. PMID: 35181623.
3. 3. Kankotia S, Stacpoole PW. Dichloroacetate and cancer: new home for an orphan drug? Biochim Biophys Acta. 2014 Dec;1846(2):617-29. doi: 10.1016/j.bbcan.2014.08.005.
4. 4. Tataranni T, Piccoli C. Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications. Oxid Med Cell Longev. 2019 Nov 14; 2019:8201079. doi: 10.1155/2019/8201079. PMID: 31827705; PMCID: PMC6885244.

About Dichloroacetate (DCA; SL-1009) 

DCA, a pan- PDK inhibitor, has the potential to be the 1^st approved medication for the mitochondrial disease PDCD and will be available as an oral solution.  Gene mutations in the mitochondrial Pyruvate Dehydrogenase Complex (PDC) lead to congenital PDCD. However, PDC is also inhibited by PDKs, that may be over-expressed in PDCD. DCA inhibits PDKs to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. DCA dosing is based on a proprietary genetic test that dichotomizes subjects into “fast” and “slow” drug metabolizers, providing individualized dosing.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda.  Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases.  Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations.  For more information, visit www.saolrx.com.

About Medosome Biotec

Medosome Biotec, LLC is a privately held, preclinical and early-stage clinical pharmaceutical company with operations in Alachua, FL and Bloomington, IN.  The Company focuses on pediatric diseases with an emphasis on developing and offering genetic tests for diagnosing rare diseases and providing personalized dosing of pharmaceutical drugs.  For more information, visit www.mdbiotec.com

Media contact:  Brian Nappi, Senior Vice President Strategy, bnappi@saolrx.com