Pipeline

With a broad product pipeline, Seelos is well-positioned to address unmet needs in multiple CNS disorders and in rare diseases. The Company is advancing late-stage therapeutic candidates with proven mechanisms of action, including:

• SLS-002: intranasal racemic ketamine for patients with suicidality in post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). The clinical development program for SLS-002 includes two parallel healthy volunteer studies, expected to be followed by pivotal registration studies after an end-of-phase II meeting with the U.S. Food and Drug Administration (FDA). SLS-002 has shown promising efficacy in suicidality (with depression) with an unremarkable safety profile. Ketamine’s rapid antidepressant action is independent of NMDAR inhibition and involves early and sustained activation of AMPAR activation. With no other drugs currently approved in this indication, SLS-002 has the potential to address approximately 600,000 cases of suicidality in U.S. emergency rooms alone each year.

• SLS-004: An all-in-one lentiviral vector, SLS-004 targets DNA-methylation editing within intron 1. The system is based on CRISPR-dCas9 fused with the catalytic domain of DNA methyltransferase 3A (DNMT3A), an enzyme that can methylate. The system is delivered to dopaminergic neurons derived from human induced pluripotent stem cells (hiPSCs) from a PD patient. As a result, the expression of SNCA is modified and disease-related cellular-phenotypes characteristics of the neurons are reversed.

The SNCA gene, that encodes the expression of alpha-synuclein, has been implicated as a highly significant risk factor for PD. In addition, accumulating evidence suggests that elevated levels of wild-type alpha-synuclein are causative in the pathogenesis of Parkinson’s disease. The role of SNCA overexpression in PD pathogenesis and the need to maintain normal physiological levels of alpha-synuclein protein emphasize the so-far unmet need to develop new therapeutic strategies, such as SLS-004, targeting the regulatory mechanisms of SNCA expression.

• SLS-005: Trehalose is a protein stabilizer that also activates autophagy and crosses the blood-brain-barrier. Based on the pre-clinical and in-vitro studies, there is a sound scientific rationale for developing trehalose for the treatment of Sanfilippo syndrome. is a low molecular weight disaccharide (.342 kDa) that protects against pathological processes in cells. It has been shown to penetrate muscle and cross the blood brain barrier. In animal models of several diseases associated with abnormal cellular-protein aggregation, it has been shown to reduce pathological aggregation of misfolded proteins as well as to activate autophagy pathways through the activation of Transcription Factor EB (“TFEB”), a key factor in lysosomal and autophagy gene expression. Activation of TFEB is an emerging therapeutic target for a number of diseases with pathologic accumulation of storage material.

Trehalose 90 mg/mL IV solution has demonstrated promising clinical potential in prior phase 2 clinical development for oculopharyngeal muscular dystrophy (OPMD) and spinocerebellar ataxia type 3 (SCA3, also called Machado Joseph disease), with encouraging safety and efficacy results thus far. These pathological proteins aggregate within cells, eventually leading to cell death. Prior preclinical studies indicate that this platform has the potential to prevent mutant protein aggregation in other devastating PolyA/PolyQ diseases.

Two U.S. patents for parental administration of trehalose exist for patients with OPMD and SCA3; both are expected to expire in 2033. In addition, Orphan Drug Designation for OPMD and SCA3 has been secured in the U.S. and in the EU.

Seelos assumed a collaborative agreement with Team Sanfilippo Foundation (TSF), a nonprofit medical research foundation founded by parents of children with Sanfilippo syndrome. TSF, upon approval by the FDA, plans to begin an open label, Phase 2(b) clinical trial in up to 20 patients with Sanfilippo syndrome and Seelos will provide the clinical supply of trehalose. The terms of the agreement entitle Seelos access to all clinical data from this trial.

• SLS-006: Our first-in-class, small molecule, partial dopamine agonist for Parkinson’s disease has successfully completed phase II studies. Seelos intends to meet with the FDA and the European Medicines Authority (EMA) to discuss the plans for pivotal registration studies to commence in 2019. SLS-006 has shown remarkable efficacy in early-stage Parkinson’s disease patients as a monotherapy and as a potential adjunctive therapy in late-stage Parkinson’s disease patients upon co-administration with a low dosage of L-Dopa.

• SLS-007: Seelos expects to begin to evaluate this peptide-based approach targeting the NACore (nonamyloid component core) in Parkinson's disease (PD) in a proof of concept, in-vivo delivery of SLS-007 in a PD transgenic mice model

• SLS-008: Our once-daily, oral CRTH2 (Chemo-attractant Receptor-homologous molecule expressed on TH2 cells) that focuses on an undisclosed pediatric orphan indication. Seelos has a “family” of compounds under its SLS-008 program. Seelos intends to file an Investigational New Drug (IND) Application in this pediatric orphan indication with a highly unmet need for an effective oral therapy.

In 2016, Seelos established a multi-program partnership with Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) forming the basis for Seelos’ lead programs. Ligand has an established track record of licensing foundational assets at the early stages of company formation. The license agreement grants Seelos worldwide rights to develop and commercialize the SLS-006, -008, -010 and -012 programs from Ligand. Ligand is a shareholder of Seelos pursuant to a cash investment and an equity milestone payment from Seelos and is entitled to other potential future milestones and royalties for licensed programs.