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

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, February 13, 2023 – Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, is proud to announce it has received the 2023 Innovation Award from the Center for Global Health Innovation’s (CGHI) Office of Life Sciences and Digital Health. CGHI - formerly known as Georgia Bio - is the state’s life science trade association.

The Innovation Award is presented to the “department, institution, company or individuals who are forging new ground by thinking outside traditional paradigms to create some unique technology.”

“We are honored to receive the 2023 Innovation Award from the Center for Global Health Innovation,” stated Saol Therapeutics CEO David Penake. “2022 was a transformational year for our company which has set Saol up for a tremendous future. It’s a wonderful honor for each employee at Saol to know that their hard work and progress in bringing new therapies to patients is being recognized.”

“The life science industry in Georgia is booming and a significant amount of that growth is due to the team at CGHI,” added Penake. “They are doing an unbelievable job driving new investment and growth in this space and to be recognized by a group that we align with and admire is incredibly meaningful to all of us at Saol.”

In 2022, Saol Therapeutics transformed from a global commercial organization to a late-stage development company. In the last 18 months, Saol divested all commercialized assets as well as two development programs, including one of which that was recently approved by the FDA. The proceeds from the transactions have fully funded current research activities for development programs SL-1002 and SL-1009. SIL-1002 is in two separate phase II studies in adult patients, one studying its effect for knee pain associated with osteoarthritis and the other for the treatment of spasticity. SIL-1009 is in a Phase III trial for a rare pediatric mitochondrial disease that recently completed enrollment, and a Phase II trial in glioblastoma. The topline results for all these studies are expected later in 2023.

The award will be presented when CGHI celebrates its 25th annual Golden Helix Awards on Wednesday, March 29th at the Fox Theatre in Atlanta, GA.

To view the press release from CGHI, including a list of all the 2023 honorees, please click here.

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.

SL-1002 is also being concurrently studied for the treatment of limb spasticity in the Phase II RAISE Trial – topline data for both studies (pain and spasticity) is expected in 2023

ROSWELL, Ga, DUBLIN and HAMILTON, Bermuda, August 9, 2022 / PRNewswire/ -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, announced today that the first patient has been enrolled in the company’s Phase II COMPASS Osteoarthritis Pain Trial.

SL-1002 is a novel, proprietary chemoneurolytic injection currently under development at Saol Therapeutics and is being evaluated in the COMPASS Osteoarthritis Pain Trial.  The trial is a multi-center, 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).  The first patient in the trial was enrolled at the International Spine, Pain and Performance Center in Washington, D.C.

“Our center is proud to enroll the first patient in Saol Therapeutics’ COMPASS Osteoarthritis Pain Trial,” said Investigator Mehul J. Desai, MD, President of the International Spine, Pain & Performance Center in Washington, D.C.  “Pain related to osteoarthritis of the knee is a condition that impacts millions of Americans, and while we have current approved treatments, there is a significant opportunity to improve on how we treat this population.  We’re excited to partner with Saol Therapeutics and the rest of the investigators around the United States in evaluating the potential of SL-1002.”

Efficacy and safety are the two primary endpoints in the study.  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 in comparison to placebo when used for the treatment of knee pain associated with osteoarthritis.  Additional secondary measures include improvements in function, concomitant medication and healthcare utilization.

“We are very enthusiastic to be partnering with Saol Therapeutics to investigate the use of SL-1002 in the COMPASS Osteoarthritis Pain Trial,” said Principal Investigator Zachary McCormick, MD, Vice Chair and Associate Professor of Physical Medicine and Rehabilitation at the University of Utah.  “There have been significant recent advancements in our understanding of the neuroanatomy of the knee with implications for enhancing the non-operative treatment of chronic knee pain due to osteoarthritis.  While treatments have improved in the past decade, there remains a need for additional safe and more effective options that can be delivered in an efficient and patient-friendly way.”

“The COMPASS Osteoarthritis Pain Trial marks another step in our commitment to develop innovative therapies for patients and the clinicians that treat them,” said Saol Therapeutics CEO David Penake.

In addition to the COMPASS Osteoarthritis Pain Trial, Saol Therapeutics recently announced that the first patient was enrolled in the RAISE Spasticity Trial (NCT05311215), evaluating the safety, pharmacokinetic and efficacy profile of SL-1002 in adult patients with limb spasticity.  Enrollment has advanced through completion of the first patient cohort.

“SL-1002 is a very exciting program.  Along with our announcement today that we have commenced enrollment in the COMPASS Osteoarthritis Pain Trial, in parallel we are rapidly enrolling patients in the RAISE Spasticity Trial,” added Penake.  “Beyond these two indications under investigation, our physician collaborators continue to stress to us that the characteristics of this novel agent may have broad applicability in multiple potential use cases.  With the committed partnership of these thought leading collaborators, and the efforts of the Saol team, we plan to complete these studies and evaluate further indications as we approach our pivotal programs in spasticity and osteoarthritis knee pain.”

Saol Therapeutics currently expects topline results of both the COMPASS Osteoarthritis Pain Trial and the RAISE Spasticity Trial to readout in 2023.

About COMPASS Osteoarthritis Pain Trial

The COMPASS Osteoarthritis 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 3^rd 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).

The primary endpoint is the overall safety profile of a single treatment exposure of SL-1002 in comparison to placebo.  Secondary endpoints include, but are not limited to, measures such as the Modified Ashworth Score (MAS), Clinical Global Impression of Change (CGI-C) and the Tardieu scale.  Additional secondary measures include the characterization of the human pharmacokinetics and pharmacodynamics relating to metabolism and clearance of SL-1002 and its metabolites.

About SL-1002

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

BRIDGEWATER, N.J. & ROSWELL, Ga., January 5, 2022 --(BUSINESS WIRE)-- Amneal Pharmaceuticals, Inc. (NYSE: AMRX) (“Amneal”) and Saol Therapeutics, a private specialty pharmaceutical company (“Saol”), today announced a definitive agreement under which Amneal will acquire Saol’s Baclofen franchise, including Lioresal^® and LYVISPAH^TM as well as a pipeline product under development. The acquisition expands Amneal’s commercial institutional and specialty portfolio in neurology while adding commercial infrastructure in advance of its entry into the biosimilar institutional market. The transaction is expected to be accretive to Amneal’s adjusted EBITDA and adjusted earnings per share results for 2022.

Lioresal^® is an intrathecal baclofen product delivered through an implantable intrathecal pump for use in the management of severe spasticity of cerebral or spinal origin for the institutional market. It has approximately $25 million in annual net revenue. LYVISPAH^TM is a baclofen oral granules (5, 10 and 20 mg) specialty product recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of spasticity. The product is expected to launch in 2022 leveraging Amneal’s neurology commercial team. Together, Amneal expects these two products to generate between $40 and $50 million in combined annual net revenues by 2025.

As part of the transaction, Amneal is adding Saol’s experienced institutional commercial team for Lioresal^® that can be utilized to support future product launches, including three oncology biosimilar products, filgrastim (biosimilar for Neupogen^®), pegfilgrastim (biosimilar for Neulasta^®) and bevacizumab (biosimilar for Avastin^®). Amneal expects to launch all three biosimilars in 2022, subject to approval by FDA.

“This acquisition is highly aligned with Amneal’s long-term growth strategy adding to our specialty and biosimilars businesses. In specialty, we see LYVISPAH^TM fitting well with our neurology portfolio and pipeline. In addition, Lioresal^® is a durable product with a long-established presence in the institutional market that we look to leverage as we prepare to commercialize our biosimilars in 2022 and beyond,” said Chirag and Chintu Patel, Co-Chief Executive Officers.

“For over 5 years, the Saol team has worked to reinvigorate the Lioresal^® brand and develop new treatment options, like LYVISPAH^TM, for patients struggling with spasticity. We are excited to see these products find their new home at Amneal along with many of our team members that have been critical to our success,” said David Penake, CEO of Saol Therapeutics.

Baclofen is a skeletal muscle relaxant used to treat muscle spasms caused by spinal cord injury, multiple sclerosis, and other conditions. It was first approved by the FDA in 1977. Important Safety Information includes a boxed warning on abrupt discontinuation, which can result in sequalae and in rare cases, has advanced to multiple organ-system failure and death. Reported adverse drug reaction includes convulsion, hypotension, hypotonia, somnolence, dizziness, nausea and headache. Animal data indicates it may cause fetal harm.

See Package Insert (PI) for full prescribing information including boxed warning and complete safety information:

Lioresal^®: https://lioresal.com/wp-content/uploads/2019/03/Lioresal-PI-01-2019.pdf

LYVISPAH^TM: https://lyvispah.com/content/uploads/2021/11/LYVISPAH-USPI-NOVEMBER-2021-FDA-approved.pdf

Terms of the Transaction

Under the terms of the transaction, Amneal will pay approximately $83.5 million of cash at close, and certain royalties (low double-digits) based on annual net sales for certain acquired products. The transaction will be financed with cash on hand and is expected to close in the first quarter of 2022, subject to the satisfaction of customary closing conditions, including clearance under the Hart-Scott Rodino Antitrust Improvements Act.

Advisors

Morgan Lewis & Bockius LLP served as legal counsel to Amneal. SVB Leerink served as exclusive financial advisor and Mayer Brown LLP served as legal counsel to Saol Therapeutics.

About Amneal Pharmaceuticals, Inc.

Amneal Pharmaceuticals, Inc. (NYSE: AMRX), headquartered in Bridgewater, NJ, is a fully-integrated essential medicines company. We make healthy possible through the development, manufacturing, and distribution of generic and specialty pharmaceuticals, primarily within the United States. The Company has a diverse portfolio of approximately 250 products in its Generics segment and is expanding across a broad range of complex products and therapeutic areas, including injectables and biosimilars. In its Specialty segment, Amneal has a growing portfolio of branded pharmaceutical products focused primarily on central nervous system and endocrine disorders, with a pipeline focused on unmet needs. Through its AvKARE segment, the Company is a distributor of pharmaceuticals and other products for the U.S. federal government, retail, and institutional markets. For more, please visit www.amneal.com.

About Saol Therapeutics

Saol Therapeutics (pronounced "Sail") is a privately held, biopharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on commercial and clinical development activity in central nervous system disorders such as spasticity, pain management, and orphan diseases. Saol has a robust pipeline of novel, mid-to-late stage development programs in osteoarthritis, focal spasticity and pyruvate dehydrogenase complex deficiency (PDCD). For more information, visit www.saolrx.com.

Cautionary Statement on Forward-Looking Statements

Certain statements contained herein, regarding matters that are not historical facts, may be forward-looking statements (as defined in the U.S. Private Securities Litigation Reform Act of 1995). Such forward-looking statements include statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future, including among other things: discussions of future operations; expected operating results and financial performance; impact of planned acquisitions and dispositions; whether and when the required regulatory approvals will be obtained; whether and when the other closing conditions will be satisfied and whether and when the transaction will close; whether and when the Company will be able to realize the expected financial results and accretive effect of the transaction; how customers, competitors, suppliers and employees will react to the acquisition; the Company’s strategy for growth; product development; regulatory approvals; market position and expenditures. Words such as “plans,” “expects,” “will,” “anticipates,” “estimates” and similar words are intended to identify estimates and forward-looking statements.

The reader is cautioned not to rely on these forward-looking statements. These forward-looking statements are based on current expectations of future events. If the underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of the Company.

Such risks and uncertainties include, but are not limited to: the impact of the COVID-19 pandemic; the impact of global economic conditions; our ability to successfully develop, license, acquire and commercialize new products on a timely basis; our ability to obtain exclusive marketing rights for our products; the competition we face in the pharmaceutical industry from brand and generic drug product companies, and the impact of that competition on our ability to set prices; our ability to manage our growth through acquisitions and otherwise; our dependence on the sales of a limited number of products for a substantial portion of our total revenues; the risk of product liability and other claims against us by consumers and other third parties; risks related to changes in the regulatory environment, including U.S. federal and state laws related to healthcare fraud abuse and health information privacy and security and changes in such laws; changes to FDA product approval requirements; risks related to federal regulation of arrangements between manufacturers of branded and generic products; the impact of healthcare reform and changes in coverage and reimbursement levels by governmental authorities and other third-party payers; the continuing trend of consolidation of certain customer groups; our reliance on certain licenses to proprietary technologies from time to time; our dependence on third-party suppliers and distributors for raw materials for our products and certain finished goods; our dependence on third-party agreements for a portion of our product offerings; our ability to identify, make and integrate acquisitions of or investments in complementary businesses and products on advantageous terms; legal, regulatory and legislative efforts by our brand competitors to deter competition from our generic alternatives; the significant amount of resources we expend on research and development; our substantial amount of indebtedness and our ability to generate sufficient cash to service our indebtedness in the future, and the impact of interest rate fluctuations on such indebtedness; the impact of severe weather; and the high concentration of ownership of our Class A Common Stock and the fact that we are controlled by the Amneal Group. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and in its subsequent reports on Forms 10-Q and 8-K. Investors are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Forward-looking statements included herein speak only as of the date hereof and we undertake no obligation to revise or update such statements to reflect the occurrence of events or circumstances after the date hereof.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220104005935/en/

Anthony DiMeo
Senior Director, Investor Relations
anthony.dimeo@amneal.com

Source: Amneal Pharmaceuticals, Inc.

Saol sales team to promote Dysport® for select approved therapeutic indications in U.S. hospitals

BASKING RIDGE, N.J., June 30, 2017 – Ipsen Biopharmaceuticals, Inc., an affiliate of Ipsen SA (Euronext: IPN; ADR: IPSEY) (Ipsen), today announced that it has entered into an exclusive, three-year agreement with Saol Therapeutics Inc. to promote Dysport® (abobotulinumtoxinA) for injection for approved therapeutic indications in adult spasticity and pediatric lower limb spasticity in the United States.

“By adding the Saol team's extensive experience with physicians in the hospital setting to our existing efforts, we are able to educate more U.S. healthcare professionals on Dysport® ,” said Cynthia Schwalm, President, North American Commercial Operations, Ipsen. “As the only botulinum toxin approved by the FDA for the treatment of spasticity in adults in upper and lower limbs, and also for the treatment of lower limb spasticity in children ages two and older, it is critical to raise awareness of Dysport® as a potential option for appropriate patients.”

Dysport® and all botulinum toxin products have a Boxed Warning which states that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Those symptoms include swallowing and breathing difficulties that can be life-threatening. Dysport® is contraindicated in patients with known hypersensitivity to any botulinum toxin preparation or to any of the components; or in the presence of infection at the proposed injection site(s); or in patients known to be allergic to cow's milk protein. The potency Units of Dysport® are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products. Please see below for additional Important Safety Information.

Under the terms of the agreement, Saol’s sales force will promote Dysport® to healthcare professionals largely in the hospital setting beginning August 2017. Ipsen will maintain its current number of sales representatives fully dedicated to Dysport® including all its therapeutic indications. Additional details of the agreement are not disclosed.

Based in Roswell, GA, Saol Therapeutics is a privately held specialty pharmaceutical company focused on providing therapies to patients with unmet medical needs. The company has a strategic emphasis on spasticity and neurologic areas. Saol currently markets Lioresal® Intrathecal (baclofen injection), the first FDA-approved intrathecal baclofen for the treatment of severe spasticity. By detailing both products, Saol believes it can further support healthcare professionals and the patients they serve with forms of spasticity that each product is FDA approved to treat.

“At Saol, we are committed to the treatment of patients with spasticity. As a cornerstone to that, we believe it is important that physicians are made aware of available treatment options,” said Saol Therapeutics Chief Executive Officer, David Penake. “Our agreement with Ipsen helps us in PRESS RELEASE 2 that mission. It also allows us to align with a company that matches our passion for doing everything we can to support and educate physicians. We look forward to working with Ipsen and growing our organization, with the goal of helping patients in the United States.”

Please find included Important Safety Information – including BOX WARNINGS – for Dysport® and Lioresal® Intrathecal (baclofen injection).

About Dysport® (abobotulinumtoxinA) for Injection

Dysport® is an injectable form of botulinum toxin type A (BoNT-A), which is isolated and purified from Clostridium bacteria producing BoNT-A. It is supplied as a lyophilized powder. Dysport® has approved indications in the United States for the treatment of adults with Cervical Dystonia (CD) and for the treatment of spasticity in adult patients. Dysport® is also the first and only FDAapproved botulinum toxin for the treatment of lower limb spasticity in pediatric patients two years of age and older.

About IPSEN CARES ®

IPSEN CARES® (Coverage, Access, Reimbursement, & Education Support) is dedicated to ensuring patients, providers and caregivers have the resources needed to help access the Ipsen medications that are critical to managing their conditions. IPSEN CARES® is staffed Monday to Friday by experts who can assist with a broad range of medical, educational, logistical and coverage information regarding Ipsen medicines. Involving the entire treatment team that surrounds patients on a daily basis, IPSEN CARES® can provide benefits verification (research of a patient’s medical or pharmacy benefit insurance coverage); prior authorization information; a patient assistance program (free medications for uninsured patients); co-pay assistance programs for eligible patients; billing and coding support; coordination with specialty pharmacies. Additional information is also available by visiting (http://www.ipsencares.com).

INDICATIONS AND IMPORTANT SAFETY INFORMATION

DYSPORT® INDICATIONS

Dysport® (abobotulinumtoxinA) for injection is indicated for the treatment of:

• Spasticity in adult patients
• Adults with cervical dystonia
• Lower limb spasticity in pediatric patients 2 years of age and older.

The safety and effectiveness of Dysport® injected into upper limb muscles or proximal muscles of the lower limb for the treatment of spasticity in pediatric patients has not been established.

Safety and effectiveness in pediatric patients with lower limb spasticity below 2 years of age have not been evaluated. Safety and effectiveness in pediatric patients with cervical dystonia or upper limb spasticity have not been established.

IMPORTANT SAFETY INFORMATION

Warning: Distant Spread of Toxin Effect Postmarketing reports indicate that the effects of Dysport® and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have 3 been reports of death. The risk of symptoms is probably greatest in children treated for spasticity, but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including upper limb spasticity in children, and in approved indications, cases of spread of effect have been reported at doses comparable to lower than the maximum recommended total dose.

Contraindications

Dysport® is contraindicated in patients with known hypersensitivity to any botulinum toxin preparation or to any of the components; or in the presence of infection at the proposed injection site(s); or in patients known to be allergic to cow’s milk protein. Hypersensitivity reactions including anaphylaxis have been reported.

Warnings and Precautions

Lack of interchangeability between botulinum toxin products

The potency Units of Dysport® are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products, and, therefore, units of biological activity of Dysport® cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method.

Dysphagia and Breathing Difficulties

Treatment with Dysport® and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant side effects occur, additional respiratory muscles may be involved (see Boxed Warning). Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several weeks, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech, or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin.

Pre-existing Neuromuscular Disorders

Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junction disorders (eg, myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of Dysport® .

Human Albumin and Transmission of Viral Diseases

This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases and variant Creutzfeldt-Jakob disease (vCJD). There is a theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD), but if that risk actually exists, the risk of transmission would also be considered extremely remote. No cases of transmission of viral diseases, CJD, or vCJD have ever been identified for licensed albumin or albumin contained in other licensed products.

Intradermal Immune reaction

The possibility of an immune reaction when injected intradermally is unknown. The safety of Dysport® for the treatment of hyperhidrosis has not been established. Dysport® is approved only for intramuscular injection.

Adverse reactions

Most common adverse reactions (≥2% and greater than placebo in either Dysport® group) in adults with upper limb spasticity for Dysport® 500 Units, Dysport® 1000 Units, and Placebo, respectively, were: nasopharyngitis (4%, 1%, 1%), urinary tract infection (3%, 1%, 2%), muscular weakness (2%, 4%, 1%), musculoskeletal pain (3%, 2%, 2%), dizziness (3%, 1%, 1%), fall (2%, 3%, 2%), and depression (2%, 3%, 1%).

Most common adverse reactions (≥ 5% and greater than placebo in either Dysport® group) in adults with lower limb spasticity for Dysport® 1000 Units, Dysport® 1500 Units, and Placebo, respectively, were: falls (9%, 6%, 3%), muscular weakness (2%,7%, 3%), pain in extremity(6%, 6%, 2%). Muscular weakness was reported more frequently in women (10%) treated with 1500 units of Dysport compared to men (5%). Most common adverse reactions (≥5% and greater than placebo) in adults with cervical dystonia for Dysport® 500 Units and Placebo, respectively, were: muscular weakness (16%, 4%), dysphagia (15%, 4%), dry mouth (13%, 7%), injection site discomfort (13%, 8%), fatigue (12%, 10%), headache (11%, 9%), musculoskeletal pain (7%, 3%), dysphonia (6%, 2%), injection site pain (5%, 4%), and eye disorders (7%, 2%).

Most common adverse reactions (≥10% in any group and greater than placebo) in pediatric patients with lower limb spasticity for Dysport® 10 Units/kg, 15 Units/kg, 20 Units/kg, or 30 Units/kg; and Placebo, respectively, were: upper respiratory tract infection (9%, 20%, 5%, 10%, 13%), nasopharyngitis (9%, 12%,16%, 10%, 5%), influenza (0%, 10%, 14%, 3%, 8%), pharyngitis (5%, 0%,11%, 3%, 8%), cough (7%, 6%, 14%, 10%, 6%), and pyrexia (7%, 12%, 8%, 7%, 5%).

Drug interactions

Co-administration of Dysport® and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like agents), or muscle relaxants, should be observed closely because the effect of botulinum toxin may be potentiated. Use of anticholinergic drugs after administration of Dysport® may potentiate systemic anticholinergic effects such as blurred vision. The effect of administering different botulinum neurotoxins at the same time or within several months of each other is unknown. Excessive weakness may be exacerbated by another administration of botulinum toxin prior to the resolution of the effects of a previously administered botulinum toxin. Excessive weakness may also be exaggerated by administration of a muscle relaxant before or after administration of Dysport® .

Use in Pregnancy

Based on animal data Dysport® may cause fetal harm. There are no adequate and wellcontrolled studies in pregnant women. Dysport® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pediatric Use

Based on animal data Dysport® may cause atrophy of injected and adjacent muscles; decreased bone growth, length, and mineral content; delayed sexual maturation; and decreased fertility.

Geriatric Use

In general, elderly patients should be observed to evaluate their tolerability of Dysport® , due to the greater frequency of concomitant disease and other drug therapy. Subjects aged 65 years and over who were treated with DYSPORT® for lower limb spasticity reported a greater percentage of fall and asthenia as compared to those younger (10% versus 6% and 4% versus 2%, respectively).

To report SUSPECTED ADVERSE REACTIONS or product complaints, contact Ipsen at 1-855- 463-5127. You may also report SUSPECTED ADVERSE REACTIONS to the FDA at 1-800- FDA-1088 or www.fda.gov/medwatch.

Please see Dysport® Full Prescribing Information including Boxed Warning and Medication Guide.

INDICATIONS AND IMPORTANT SAFETY INFORMATION

Lioresal® Intrathecal (baclofen injection)

Indications and Usage

• Lioresal® Intrathecal (baclofen injection) is a muscle relaxant and antispastic that is indicated for use in the management of severe spasticity of cerebral or spinal origin.
• Lioresal® Intrathecal is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only in implantable pumps approved by the FDA specifically for the administration of Lioresal® Intrathecal into the intrathecal space.
• Lioresal® Intrathecal via an implantable pump should be reserved for patients unresponsive to oral baclofen therapy or those who experience intolerable CNS side effects at effective doses.
• Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy.
• Prior to implantation of a device for chronic intrathecal infusion of Lioresal® Intrathecal, patients must show a response to Lioresal® Intrathecal in a screening trial. Please review the dosing and administration section of the Lioresal® Intrathecal prescribing information for further details.

Contraindications

Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death.

Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. Special attention should be given to patients at apparent risk (e.g. spinal cord injuries at T-6 or above, communication difficulties, history of withdrawal symptoms from oral or intrathecal baclofen). Consult the technical manual of the implantable infusion system for additional postimplant clinician and patient information (see WARNINGS).

• Hypersensitivity to baclofen
• Lioresal® Intrathecal is not recommended for intravenous, intramuscular, subcutaneous or epidural administration.

Select Warnings and Precautions

• It is mandatory that all patients, caregivers, and treating physicians receive adequate information regarding the risks of the mode of treatment. Instruction should be given on signs and symptoms of overdose, procedures to be followed in the event of an overdose, and proper home care of the pump and insertion site.
• Due to the possibility of life-threatening CNS depression, cardiovascular collapse, and/or respiratory failure, physicians must be adequately trained and educated in chronic intrathecal infusion therapy.
• Patients should be infection-free prior to both a screening trial and a pump implantation. The presence of infection may interfere with an assessment of the patient’s response to bolus Lioresal® Intrathecal, increase the risk of surgical complications and complicate dosing.
• Reservoir refilling must be performed by fully trained and qualified personnel following the directions provided by the pump manufacturer. Extreme caution must be used when filling an FDA approved implantable pump, following strict aseptic technique and ensuring refill directly into the reservoir and not the catheter access port.
• An attempt should be made to discontinue concomitant oral antispasticity medication to avoid possible overdose or adverse drug interactions, either prior to screening or following implant and initiation of chronic Lioresal® Intrathecal infusion.
• Following pump implantation, and for each adjustment of the dosing rate of the pump and/or concentration of Lioresal® Intrathecal, the patient should be monitored closely until it is certain the patient’s response to the infusion is acceptable and reasonably stable.
• Early symptoms of baclofen withdrawal may include return of baseline spasticity, pruritus, hypotension and paresthesias.
• Priapism may develop or recur if treatment with intrathecal baclofen is interrupted.
• Signs of overdose may appear suddenly or insidiously, and a massive overdose may present as coma. Less sudden and/or less severe forms of overdose may present with signs of drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral progression of hypotonia and loss of consciousness progressing to coma.
• Should overdose appear likely, the patient should be taken immediately to a hospital for assessment and emptying of pump reservoir.
• Except in overdose related emergencies, the dose of Lioresal® Intrathecal should ordinarily be reduced slowly if the drug is discontinued for any reason.

Adverse Reactions Common Adverse Reactions

• The most frequent drug adverse events vary by indication but include: hypotonia (34.7%), somnolence (20.9%), headache (10.7%), convulsion (10.0%), dizziness (8.0%), urinary retention (8.0%), nausea (7.3%), and paresthesia (6.7%). Dosing and programming errors may result in clinically significant overdose or withdrawal. Acute massive overdose may result in coma and may be life threatening.
• Drowsiness has been reported in patients on Lioresal® Intrathecal. Patients should be cautioned regarding the operation of automobiles or other dangerous machinery and activities made hazardous by decreased alertness. Patients should also be cautioned that the central nervous system depressant effects of Lioresal® Intrathecal may be additive to those of alcohol and other CNS depressants.

Serious Adverse Reactions

• Seizures have been reported during overdose and with withdrawal from Lioresal® Intrathecal as well as in patients maintained on therapeutic doses of Lioresal® Intrathecal.
• Fatalities have been reported with Lioresal® Intrathecal use.

Postmarketing Experience

• The following adverse events have been reported during post-approval use of Lioresal® Intrathecal. o Musculoskeletal
  • The onset of scoliosis or worsening of a pre-existing scoliosis has been reported. o Urogenital
  • Sexual dysfunction in men and women including decreased libido and orgasm dysfunction have been reported.

Use in Specific Populations

• There are no adequate and well controlled studies in pregnant women. Lioresal® Intrathecal should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Nursing mothers should exercise caution, as oral baclofen has been shown to pass into milk at therapeutic doses. ▪ Safety and effectiveness in pediatric patients below the age of 4 have not been established.
• Patients suffering from psychotic disorders, schizophrenia, or confusional states should be treated cautiously with Lioresal® Intrathecal and kept under careful surveillance.
• Lioresal® Intrathecal should be given with caution in patients with impaired renal function. Dose reduction may be necessary.
• Lioresal® Intrathecal should be used with caution in patients with a history of autonomic dysreflexia.

For more information, including BOX WARNING, refer to Lioresal® Intrathecal (baclofen injection) prescribing information, located here.

About Ipsen in North America

Ipsen Biopharmaceuticals, Inc. is the US affiliate of Ipsen, a global specialty-driven biopharmaceutical group. The US head office is located in Basking Ridge, New Jersey. Ipsen Biopharmaceuticals Canada, Inc. is an integrated business unit within North America and has its head office located in Mississauga, Ontario. Ipsen Bioscience, Inc., the Ipsen US research and development center focused on the discovery of highly differentiated and competitive products in oncology and rare diseases, is located in Cambridge, Massachusetts. At Ipsen Bioscience, we focus on creating a highly cooperative and passionate R&D organization through partnerships, innovation, and continuous learning to effectively deliver new treatments for patients. At Ipsen, we focus our resources, investments, and energy on discovering, developing, and commercializing new therapeutic options for oncologic, neurologic, and endocrine diseases. For more information on Ipsen in North America, please visit www.ipsenus.com or www.ipsen.ca.

About Ipsen

Ipsen is a global specialty-driven biopharmaceutical group focused on innovation and specialty care. The group develops and commercializes innovative medicines in three key therapeutic areas - Oncology, Neurosciences and Rare Diseases. Its commitment to oncology is exemplified through its growing portfolio of key therapies for prostate cancer, neuroendocrine tumors, renal cell carcinoma and pancreatic cancer. Ipsen also has a well-established Consumer Healthcare business. With total sales close to €1.6 billion in 2016, Ipsen sells more than 20 drugs in over 115 countries, with a direct commercial presence in more than 30 countries. Ipsen's R&D is focused on its innovative and differentiated technological platforms located in the heart of the leading biotechnological and life sciences hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US). The Group has about 5,100 employees worldwide. Ipsen is listed in Paris (Euronext: IPN) and in the United States through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information on Ipsen, visit www.ipsen.com.

Forward Looking Statements

The forward-looking statements, objectives and targets contained herein are based on the Group's management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect the Group's future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words "believes," "anticipates" and "expects" and similar expressions are intended to identify forwardlooking statements, including the Group's expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by the Group. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising product in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. The Group must face or might face competition from generic products that might translate into a loss of market share. Furthermore, the Research and Development process involves several stages each of which involves the substantial risk that the Group may fail to achieve its objectives and be forced to abandon its efforts with regards to a product in which it has invested significant sums. Therefore, the Group cannot be certain that favorable results obtained during pre-clinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the product concerned. There can be no guarantees a product will receive the necessary regulatory approvals or that the product will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the Group's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Group's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The Group also depends on third parties to develop and market some of its products which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to the Group's activities and financial results. The Group cannot be certain that its partners will fulfill their obligations. It might be unable to obtain any benefit from those agreements. A default by any of the Group's partners could generate lower revenues than expected. Such situations could have a negative impact on the Group's business, financial position or performance. The Group expressly disclaims any obligation or undertaking to update or revise any forward looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. The Group's business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers.

For further information:

Media

Marisol Peron

Vice President, North American Internal & External Communications

Tel.: 212-257-6724

E-mail: marisol.peron@ipsen.com

Elliot Fox

W2O Group

Tel.: 908-275-6330

E-mail: efox@w2ogroup.com

# # #

References

1. Martin A, et al. Epidemiological, humanistic, and economic burden of illness of lower limb spasticity in adults: a systematic review. Neuropsychiatric Disease and Treatment. 2014; 10 (111-122)
2. Sköld A, et al. Spasticity after traumatic spinal cord injury: nature, severity, and location. Archives of Physical Medicine and Rehabilitation. 1999; 80 (1548-57)
3. National Institute of Neurological Disorders and Stroke. Spasticity Information Page. https://www.ninds.nih.gov/Disorders/All-Disorders/Spasticity-Information-Page Accessed May 16, 2017.
4. Gray H. Anatomy of the Human Body. “The Muscles and Fasciæ of the Leg.” http://www.bartleby.com/107/129.html. Accessed June 23, 2016.
5. Delgado M, et al. AbobotulinumtoxinA for equinus foot deformity in cerebral palsy: A randomized clinical trial. Pediatrics. 2016;137(2).

Dysport® (abobotulinumtoxinA) for injection, for intramuscular use 300- and 500-Unit vials.

DYSPORT is a registered trademark of Ipsen Biopharm Limited.

IPSEN CARES is a registered trademark of Ipsen S.A. Lioresal® is a registered trademark of Saol International Limited Corporation.

© 2017 Ipsen Biopharmaceuticals, Inc. June 2017 DYS-US-001875