UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 11, 2016

 

 

ATYR PHARMA, INC.

(Exact name of registrant as specified in its charter)

 

 

 

 

 

(858) 731-8389

(Registrant’s telephone number, including area code)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

 

 

 

 

 

 

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Item 7.01 Regulation FD Disclosure.

aTyr Pharma, Inc. (the “Company”) intends to use an investor presentation to conduct meetings with investors, stockholders and analysts and at investor conferences, and which the Company intends to place on its website.  A copy of the presentation materials is attached hereto as Exhibit 99.1.  The Company does not undertake to update the presentation materials.  

The information under this Item 7.01, including Exhibit 99.1, is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities and Exchange Act of 1934, as amended, or the Exchange Act, or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing

Item 9.01  Financial Statements and Exhibits.  

(d)  Exhibits

 

 

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

 

 

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EXHIBIT INDEX

 

 

 

 

New Promise for Rare Disease Patients with Immune & Fibrotic Pathologies January 2016

Forward-Looking Statements The following slides and any accompanying oral presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws.  The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” “opportunity,” or “continue,” and other similar expressions are intended to identify forward-looking statements.  For example, all statements we make regarding the potential therapeutic benefits of Physiocrines and our product candidates, including Resolaris™ and iMod. Fc, the ability to successfully advance our pipeline or product candidates, the timing within which we expect to initiate, receive and report data from, and complete our planned clinical trials, and our ability to receive regulatory approvals for, and commercialize, our product candidates, our ability to identify and discover additional product candidates, and the ability of our intellectual property portfolio to provide protection are forward-looking statements. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. These risks, uncertainties and other factors are more fully described in our filings with the U.S. Securities and Exchange Commission, including our most recent Quarterly Report on Form 10-Q. The forward-looking statements in this presentation speak only as of the date of this presentation and neither we nor any other person assume responsibility for the accuracy and completeness of any forward-looking statement. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. We own various U.S. federal trademark applications and unregistered trademarks, including our company name and Resolaris™.  All other trademarks or trade names referred to in this presentation are the property of their respective owners. Solely for convenience, the trademarks and trade names in this presentation are referred to without the symbols ® and ™, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.

Tissue Restoration in Rare Diseases of Muscle & Lung Strong Team, Results Driven Physiocrine* Disruptive Opportunity Resolaris: One Protein Many Rare Diseases Autonomous Pipeline New biology, new therapeutic intervention points Natural modulators of immune & fibrotic pathways Immune/fibrotic nexus in rare muscle & lung diseases 1st in class muscle, lung & liver therapies from internal product engine Therapeutically promote tissue homeostasis and restoration iMod.Fc second product candidate in pipeline of patent protected, novel proteins Product & patient driven, rare disease expertise Unique investment thesis: rare disease business model based on newly discovered pathways aTyr Highlights *Proteins for life (physio) specific activity (crine)

Two weeks of treatment in Statin myopathy & Bleomycin IPF* models Resolaris Improves Muscle & Lung Immune/Fibrotic Components First Program Resolaris *Idiopathic Pulmonary Fibrosis (“IPF”), a subset of Interstitial Lung Disease (“ILD”)

1st in class candidates for rare diseases with an immune or fibrotic component Immuno/Fibrosis Modulation Pipeline 1 Facioscapulohumeral Muscular Dystrophy 2 Limb-girdle Muscular Dystrophy 3 Interstitial Lung Disease Therapeutic Focus Preclinical Rights Phase 1 Phase 1b/2 Discovery Paradigm shift In Treatments Worldwide Worldwide Worldwide Worldwide Liver iMod.Fc ILD Resolaris ILD3 Resolaris Adult FSHD – Long-term safety extension study Liver Patient Phenotype Focus Severe impact from disease with the potential for large treatment effect Subject to poor standard of care Worldwide Muscle Lung Resokine Pathway Worldwide Resolaris Adult FSHD1 Resolaris LGMD2 Resolaris Early Onset FSHD

Leadership Team Experienced Industry Veterans Melissa Ashlock, M.D. SVP, Translational Medicine & Therapeutics John McKew, Ph.D. VP, Research Kelly Blackburn VP, Clinical Operations Andrew Cubitt, Ph.D. VP, Product Protection Sanuj Ravindran, M.D. Chief Business Officer John Blake, CPA VP, Finance John Mendlein, Ph.D. Chief Executive Officer Ashraf Amanullah, Ph.D. VP, Manufacturing

Discovery of Physiocrine Proteins: Alternative Splicing of Ancient Genes Leads to New Biology

Dual Roles of tRNA Synthetases: Protein Synthesis & Potential for Physiological Regulation Intracellular Function: 23 genes in humans Protein synthesis tRNA Synthetases: In all cellular life forms 4 billion years old Extracellular Function: ~300 Physiocrines Splice variants offer new biology Genetic basis of Physiocrines v bacteria Protein Synthesis (retained in all species) Intracellular (Original Primordial Function) Physiocrine Regions of tRNA Synthetase displayed in a gene fish Vascular Systems (fish) worm Regenerative Systems (worm) human Immune Systems (human) Extracellular Physiological (Systems Evolved with Species) Augment Homeostatic Pathways by Administering Physiocrine Proteins Orchestrate multiple physiological processes Focus on Immuno- & Fibro-modulation Therapeutic Opportunities

Primer on Physiocrines Potential for novel physiological modulation in disease Extracellular functions of intracellular tRNA synthetases New class of modulators of tissue homeostasis Conserved, genetic gain of function over time ~300 proteins varying in size (40-500AA) Work via GPCRs, TLRs, cytokine receptors & other proteins Not glycosylated & non-canonical leader sequences At least 14/23 members of family with disease connections Potential for tissue-by-tissue homeostasis products Muscle Heart Liver Brain/CNS Lung Physiocrine Discovery

Physiocrine Mutations in Disease Organ Phenotypes Genetic Evidence of the Importance Of Physiocrines No mutations reported to date (6) CNS Muscle Heart Eye/Ear Liver Lung Domain location of mutation: Physiocrine Catalytic (may overlap with Physiocrine domain) tRNA synthetases targeted by autoantibodies

Leading Journal Publications: Science & Nature Published in Lo et al., Science, 2014; Weiwei, He, et al., Nature 2015. Graphics are visual representations for illustrative purposes.

The First Physiocrine, the Resokine Pathway: Potential New Therapies in Rare Muscle & Lung Diseases

Naturally occurring Physiocrines Resolaris™ iMod (slightly truncated from wildtype) (splice variant) ** Molecules of the Resokine Pathway New hope for rare muscle & lung disease patients Engineered Physiocrine iMod.Fc Resokine Franchise Resokine* Pathway Discovery: Immuno-modulatory & fibro-modulatory activity via in vivo screening Clinical correlates with Jo-1 Ab phenotype: myopathy & ILD where we believe the pathway is disrupted *Resokine (name for extracellular HARS, a tRNA Synthetase) **Zhou et al, JBC, 2014 Therapeutic applications with a Jo-1 Ab phenotype: Rare myopathies with an immune component (RMICs) Rare pulmonopathies with an immune component (RPICs) Pursuing subsets of ILD

aTyr unpublished data Ability to Treat Immune Cell Invasion in Muscle Control Statin days 1-14 (toxic dose) 0.3 mg/kg Resolaris days 7-14 Statin days 1-14 1.0 mg/kg Resolaris days 7-14 Statin days 1-14 3.0 mg/kg Resolaris days 7-14 Statin days 1-14 Resolaris Preclinical ê Cytokines, ê T-cells and ê Monocytes with Resolaris administration Myopathy model: in vivo Resolaris effects

Three week rodent model, two weeks of therapeutic treatment Resolaris: Active In Lung Inflammation & Fibrosis Model Experimental data provided by Stelic CRO CT scans taken at day 14, lung histology taken at day 21 * Activity of mouse Resolaris (3mg/kg) vs vehicle control Pulmonary Inflammation and Fibrosis Induced with Bleomycin Promising therapeutic activity* Compared favorably to Pirfenidone Promising Therapeutic Activity Resolaris

Clinical Development of Resolaris: Harnessing a Natural Pathway to Treat Multiple Muscle & Lung Diseases

Multiple opportunities for clinical advancement Staging Rare Muscle & Lung Disease Indications Clinical Path for Resolaris™ & iMod.Fc Early Onset FSHD Limb Girdle Muscular Dystrophy Interstitial Lung Disease Resolaris Clinical FSHD Resolaris or iMod.Fc To establish safety and tolerability in patients Resolaris Healthy Volunteer Trial Completed Adult FSHD completed dosing

Rare myopathies with an immune component (RPIC) Resolaris Clinical Resolaris for Multiple Muscle Indications Facioscapulohumeral Muscular Dystrophy (FSHD) Limb-girdle Muscular Dystrophy 2B (LGMD2B) Pathology Immune component (e.g. T-cells) Toxic loss of function mutation (dysferlin) Muscle group progression; MRI assessable Immune component (e.g. T cells) Toxic gain of function mutation (Dux4 protein) Muscle-by-muscle progression; MRI assessable Standard of care No therapeutic treatments Only supportive care provided P1b/2 trial initiated in 4Q15 First patients dosed Explore safety, tolerability, and activity Trials Adult FSHD P1b/2 completed dosing in cohort 3 Early onset FSHD P1b/2 trial initiated 4Q15 Explore safety, tolerability, and activity Clinical Debilitating muscle weakness Challenges moving limbs May have respiratory insufficiency Debilitating muscle weakness Difficulty raising arms, foot drop when walking May have visual or auditory impairment Similar clinical phenotype to Jo-1 Ab disease as both are sometimes misdiagnosed as either polymyositis or Jo-1 Ab Phenotype

LGMD2B Disease Progression Case History Difficulty rising from a chair, raising hands above head Uses a cane and leg braces Walks normally, active childhood LGMD2B Diagnosis Abnormal gait Knees locked Difficulty climbing stairs Misdiagnosed w/ polymyositis Part time wheelchair-bound Age Full dependency due to severe physical disability Steroid-induced myopathy First symptoms <15 16 – 18 19 – 27 28 - 34 Full time wheelchair-bound https://www.youtube.com/watch?v=JLqHis1yPUI http://mwtn2013blisswelch.blogspot.com/ Unable to turn over in a bed or raise hands above head Uses service dog for daily activities Slight improvement when steroids stopped Unable to rise from a chair Requires assistance in daily living

Early Onset FSHD Case History Weakness in the lower back/curvature of the spine Leg muscle weakness/walking with a limp Normal early childhood Requires full-time use of wheelchair and assisted living Diagnosed with scoliosis Muscle weakness and early speech impediment Difficulty forming facial expressions Lower limb muscle weakness/walker or chair Development of severe speech impediment Foot drop and loss of ability to stand/multiple falls Diagnosed age 8 with FSHD Part time wheelchair-bound Age First symptoms Full dependency due to severe physical disability <6 6 – 12 12 – 18 18 - 24 http://www.theguardian.com/lifeandstyle/2009/may/28/muscular-dystrophy-disability-fshd Climbing Mountains; Sarabjit Parmar, 2014 Full time wheelchair-bound

Quadriceps Immunologically driven disease progression assessed by MRI Monitoring Muscle-by-Muscle Disease Phenotype Frisullo et al., J Clin. Immunol., 2011; Also based on unpublished work and communications with investigators and KOLs Conversion to Fat/atrophy T1 for Fat/atrophy MRI Endpoints: T2 for Immune Activity Transition to Immune Activity Disease Progression Clinical Status Functional Mild weakness Severe weakness Biopsy Normal Immune cell invasion Fatty infiltration Resolaris Clinical Intervention Point

Phase 1b/2 randomized, double-blind, placebo controlled, multiple ascending dose Exploratory Study of Resolaris in Adult FSHD 3 mg/kg Weekly IV 0.3 mg/kg Weekly IV 1 mg/kg Weekly IV Cohort 1 n = 4 Cohort 2 n = 8 Cohort 3 n = 8 Cohort 4 n = 12 Cohort 5 n = 12 Resolaris Clinical COMPLETED COMPLETED Long-term Safety Extension Study 3 mg/kg Weekly IV ON-GOING Immunology Assessments Muscle & Patient Assessments Three Months Dosing Placebo Follow-Up Targeted MRI Targeted MRI Targeted MRI Optional Optional MRI Surveillance Scan MRI Surveillance Scan COMPLETED At approximately the end of 1Q 2016 safety, tolerability & activity data

Phase 1b/2 open-label, intra-patient dose escalation study LGMD2B/FSHD: Exploratory Study of Resolaris Immunology Assessments Muscle & Patient Assessments Three Month Dosing Resolaris Clinical ON-GOING Placebo FSHD n = up to 4 LGMD & FSHD n = up to 4 n = up to 4 Week 10-13 3 mg/kg Twice weekly IV Week 1 Placebo Week 2-9 Intra-patient dose escalation 0.3 – 1.0 mg/kg Weekly IV Week 2-9 Intra-patient dose escalation 0.3 – 3.0 mg/kg Weekly IV Week 1 Placebo Week 10-13 1 mg/kg Twice weekly IV MRI Surveillance Scan MRI Surveillance Scan Targeted MRI Targeted MRI Targeted MRI Targeted MRI

Phase 1b/2 open-label, intra-patient dose escalation study Early Onset FSHD: Exploratory Study of Resolaris Week 1 Placebo Week 2-13 Intra-patient dose escalation 0.3 – 3.0 mg/kg Weekly IV Resolaris Clinical ON-GOING Early Onset FSHD n = up to 16 Stage 1 Ages 16-25 n = up to 8 Immunology Assessments Muscle & Patient Assessments Three Month Dosing Placebo MRI Surveillance Scan MRI Surveillance Scan Week 2-13 Intra-patient dose escalation 0.3 – 3.0 mg/kg Weekly IV Week 1 Placebo PLANNED Stage 2 Ages 12-15 n = up to 8 (≤ 10 as age of disease onset)

Promise for grave, recalcitrant myopathy patients Resolaris: One Product, Multiple Rare Diseases Commercial 19,000 US FSHD 16,000 US LGMD 16,000 US DMD 51 45 53 44 52 50 Other exons FSHD: Average prevalence rates of FSHD are approximately 1/17,000. Applying this rate to the US population based on recent census data equals approximately 19,000. LGMD: 16,000 cases estimated in US population. 1/20,000 Wickland and Kissel, Neural. Clin. 2014. Relative Prevalence of Limb Girdle Muscular Dystrophies in the United States Population. Wicklund et al., Neurology 2013. DMD: Prevalence of approximately 5/100,000. Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2014 - Number 1 Leverage registries, sites and advocacy groups to access FSHD/LGMD patients Leverage sites for indication expansion Common physician base for patient ID, prescribing and clinical development in RMICs FSHD

Severe, rare disorders with high unmet medical need Resolaris Clinical Interstitial Lung Disease > 80 RPIC Forms Pathogenesis Lung damage leading to alveolar inflammation or fibrosis Worst prognosis: lower DLCO and rapid decline of DLCO over three years Clinical manifestations Shortness of breath and cough Specific chest radiographic abnormalities Decreased lung volume noticed in pulmonary function tests Standard of care O2 , pulmonary rehab Immunosuppressive (cyclophosphamide with low dose prednisone) Lung transplant Two Molecules Active in Lung Models: Resolaris & iMod.Fc Expect to initiate exploratory P1b/2 trial with iMod.Fc (2017) and/or Resolaris (by the end of 2016) Evaluating appropriate forms of ILD Goal is to explore safety, tolerability, biological and clinical activity Upcoming Trials

An Engineered Physiocrine for Lung Disease: iMod.Fc New TPP to open more lung indications Rationale for iMod.Fc*: Resolaris TPP: Weekly dosing; limits lung applications Develop molecule for new TPP: potentially once-monthly dosing Product Concept: Two iMod domains per Fc of an antibody Extend exposure to hit TPP Preclinical Path and Goals: Industry proven model of IPF (approved drugs: Pirfenidone & Nintedanib) E. coli produced for low COGs Show immuno- & fibro- modulatory activity Show safety at higher doses Potential Therapeutic applications: Rare pulmonopathies with an immune component (RPICs) Broader reach into RPICs and interstitial lung disease (ILD) indications Lung Resokine Franchise Rare Pulmonopathies with an Immune Component (“RPICs”) s * iMod.Fc refers to immunomodulatory domain of HARS fused to an Fc region of an antibody TPP = Target Product Profile

iMod.Fc Fc (human antibody) iMod (100% identical to human wildtype)

Second Ind Candidate iMod.Fc 1/250th of Pirfenidone dose Better than 10 TGFβ Ab doses Established IPF rodent model Improves inflammation & fibrosis Differentiated mechanism Two iMod.Fc Doses Outperform 28 Pirfenidone Doses * *The Ashcroft scale for the evaluation of bleomycin-induced lung fibrosis is the analysis of stained histological samples by visual assessment

Non-GLP double-dose study No clinical observations No pro-inflammatory cytokine signal Attractive PK iMod.Fc: Non-Human Primate and Rodent PK and Safety Supports potential for monthly dosing in patients Non-Human Primates Rodents Non-GLP toxicology 1-month study at dose level 25x efficacious dose No pro-inflammatory cytokine signal No clinical observations No changes in body or tissue weights 14 tissues examined microscopically; all normal Attractive PK

Building a New Class of Therapeutics: Foundation for the Future

Broad IP Protection for Physiocrine Composition of Matter Resolaris Program Strategic Assets for Programs and Class Global Patent Estate ~300 Physiocrines discovered Over 200 Physiocrines interrogated via protein expression and functional assays >200 pending applications worldwide 70 issued or allowed patents Claims to therapeutic compositions to block competitors Therapeutic compositions and methods of use including full length proteins Antibodies with selective binding specificity to a Physiocrine US Patent protection to 2033, without patent extensions Composition of matter patents issued or allowed in the US and Europe Comprised of a number of patent families including U.S. Patent No. 8,835,387 covering Resolaris Protecting The Future

Opportunity to own a new class of meaningful medicines Revolutionary Drugs Leveraging New Biology Pioneer New biology Insulin First product 1923 1968 1989 Coagulation factors Erythropoietin Enzyme replacement therapy TNF pathway VEGF pathway Complement pathway Physiocrine pathway 1990 1998 2004 2007 Meaningful Medicines

Immuno/Fibrosis Modulation Pipeline 1 The expected timing of the anticipated next milestones for our clinical programs for Resolaris in FSHD, LGMD and RPIC is based on our current estimates and is subject to change based upon a variety of risk factors. Therapeutic Focus Preclinical Phase 1 Phase 1b/2 Discovery Potential First-in-Class Medicines Liver Muscle Lung Resokine Pathway Status1 Expect initial data cohorts 1-3 at approx. the end of 1Q16 Resolaris LGMD Resolaris Early Onset FSHD iMod.Fc ILD (2nd IND Candidate) Resolaris ILD Liver Initiated P1b/2 in 4Q 2015 Initiated P1b/2 in 4Q 2015 Expect to initiate P1b/2 with iMod.Fc (2017) and/or Resolaris (by the end of 2016) Initiated P1b/2 in 3Q 2015 Resolaris Adult FSHD – Long-term safety extension study Resolaris in Adults with FSHD

Thank You