A horrible, painful disease

Transcription

1 October 17, 2016 House Majority Leader Kevin McCarthy Phoenix, UA Med School - Arizona Republic - Tucson Arizona Star A horrible, painful disease Raising the Standard of Care David Larwood, MS/JD/MBA, CEO John Galgiani, MD, Chairman, CMO October 13, 2016, Bakersfield, House Majority Leader Kevin McCarthy Announcing FLEET 1000 person VF trial Biotech Showcase 2017 January 10, 2017, Tuesday 4 pm San Francisco, CA

2 Valley Fever Solutions Save lives! Human data: Phase 1 showed good safety profile Ready for Phase 2a Proof of Concept (data Fall 2017) Animal data: NikZ fungicidal against VF, expect good human results Expect dramatic improvement in Standard of Care Specialty pharmaceutical company Nikkomycin Z ( NikZ ), - antifungal, effective against coccidioidomycosis (Valley Fever, cocci ), an orphan infectious disease NCE, Novel mechanism of action, primary monotherapy for Valley Fever, adjunct for many other fungi Orphan OOPD and Qualified Infectious Disease Product market exclusivity for 12 years from launch, + new patent applications Market potential in excess of $100M for first indication (VF) Geographic concentration of VF: minimal sales force 2

3 Annually Kills 150, 1,000 have no effective therapy alternatives This fungus wants to use YOU as part of its life cycle 150K Infected 50K Symptomatic 22K at particular risk All could benefit from better drugs 9K Hospitalized 1K cannot use existing drugs 150 die Strong Patient advocacy groups, KOLs 3

4 Many Complicated Infections do not Respond to Current Treatment Options Existing cocci antifungal therapies are only fungistatic limit symptoms and spread of cocci infection, but do not cure- need drugs for life Poor safety and side effect profile creates concern for long-term use 40% of Valley Fever patients do not adequately respond to any existing antifungals Drug Patent Protection Use Disadvantages Brand Name /Manufacturer Amphotericin B No IV for severe respiratory or pulmonary infection; meningitis Renal Toxicity Hypokalemia Hypomagnesaemia Chills, fever, tinnitus and headache, and about one in five patients vomit Intrathecal injections can cause neurotoxicity Abelcet /Enzon Fungizone /Apothecon Ambisome /Astellas Amphotec /Intermune Pharms Fluconazole Ketoconazole Itraconazole Voriconazole Posaconazole No No No Yes Yes Oral for subacute or chronic; to reduce the risk of extra pulmonary dissemination or to obtain remission after dissemination occurs Hepatic Toxicity Generally mild nausea, headache and abdominal pain Exfoliative skin lesions GI disturbances Pruritis Inhibition of adrenocortical steroid and testosterone synthesis with gynecomastia, impotence and low sperm count in some male patients. Adverse interactions with other drugs Visual Disturbances Diflucan/Pfizer Nizoral/Johnson & Johnson Sporanox/Johnson & Johnson Vfend/Pfizer Noxafil/Merck 4

5 High Unmet Need for New Treatment Options for Patients with Complicated Cocci Infection Uncomplicated Valley Fever infections often self-resolve, but patients have significant loss of daily function for several months Even symptomatic patients who self-resolve (~20K) still have significant loss of daily function for months, unable to work, with significant loss of daily functioning These people would welcome a useful drug For complicated infections, antifungal agents improve symptoms in about 60% of patients by arresting disease, but with significant side effects. Existing therapies do not cure underlying infection. Infection and relapse are common if treatment is stopped Current antifungals have significant side effects, with increased risk in chronic patients. 40% of patients are unresponsive to existing antifungal therapies A subset (12%) of diagnosed patients will develop more severe or disseminated infection and require chronic treatment An estimated 8,900 patients are hospitalized CDC reported average cost of hospital admission for Valley Fever is nearly $50k High readmission rate (~24%) for patients hospitalized with Valley Fever ~150 deaths annually 5

6 Overview of Coccidioidomycosis 6

7 Nikkomycin Z (NikZ) is a Novel Antifungal with Promising Preclinical Data to Support Fungicidal Activity in Cocci Nikkomycin Z is a first-in-class antifungal therapy that targets fungal cell walls, with no known impact on mammalian cells Targets underlying infection to eradicate coccidioidomycosis (not true of any current drugs) Cocci, Histo, Blasto: Novel mechanism, expect use as a standalone Candida, Aspergillus: adjunct to existing antifungal therapies to enhance efficacy Strong safety profile with no significant side effects or adverse events yet identified Good preclinical results in reliable models Fungicidal in mouse (model highly correlated with human response to existing treatments) Positive results in several pet dogs; Valley Fever commonly afflicts animals as well, particularly dogs New patent applications for improved manufacturing process Potential for a novel companion diagnostic with additional IP 7

8 Management Team David Larwood, MS, JD, MBA - CEO, BOD Managed our process improvement and scale up for NikZ to GMP-ready 2nd startup as founder, 8 years 2 NASDAQ startups MS= 4 years PhD studies at UCSF Pharmaceutical Chemistry First to make two commercial drugs John Galgiani, MD BOD Chairman, CMO 40 years research and clinical experience in medical mycology; Chairman, NIH Mycoses Study Group Coccidioidomycosis Subproject. Founder and Director, UA Valley Fever Center for Excellence (VFCE), University of Arizona College of Medicine Post-Doc Stanford University; Professor, University of Arizona College of Medicine Robert Assenzo - BOD Formerly Critical Path Institute; DIA; 30 years big pharma executive Looking to add Clinical Trial expert 8

9 Valley Fever Solutions Ready for Phase 2a Proof of Concept Late Spring 2017 Human data: good safety profile (Phase 1) Animal data: NikZ fungicidal against VF $2M support needed to run and complete Phase 2a Roadmap Phase 2a trials Proof of Principle in 8 months Set up pivotal, could start in 2017 NIH Phase 2a planned for Q3 2016, with additional NIH supported studies planned Financed to date through NIH and FDA grants ($9M, + $10M value of base Shaman transfer (IND + API)) $10-15M required to achieve Phase 3 readiness Orphan OOPD and QIDP market exclusivity for 12 years New Manufacturing IP in process 9

10 Milestones Phase 1 very clean API process refinement g scale (stimulus ARRA $$, RC3) ( 13-16: long gap in funding) 500 g scale 2017 improved API manufacturing (grant funded) running now 10 kg scale expect April/May 2017 ($500K, NIH) Packaging validation: Finalizing bids Jan Feb 17. $ K Phase 2a trial Early summer 2017, $1.4 M Readout September Phase 3 trial Late 2017 Readout Summer 2018 NDA / Conditional approval File NDA December 2018, Approval could be summer

11 More Detailed: Overview of Coccidioidomycosis Overview and Pathogenesis Commonly known as Valley Fever, Cocci is caused by inhaling microscopic spores of Coccidioides, soil dwelling fungi endemic to the southwestern US Infection is typically acquired from a single spore Symptoms & Manifestation Diagnosis 40% of infections produce a pneumonia syndrome (fever, cough, chest pain, exhaustion) that typically lasts for many weeks to months before improving A small subset of patients suffer long-term health problems; in a few cases cocci disseminates from the lungs into other tissue skin, bones, and, often fatally, the meninges of the brain. Valley fever is frequently undiagnosed or misdiagnosed as due to other causes of pneumonia Patients with respiratory illness exceeding one week may receive a serological test; however such tests frequently produce false-negative results in the first weeks of illness. Treatment Patients with severe pneumonia or those with immunosuppression and a risk of complications are typically treated with antifungal therapy (e.g., fluconazole) for three to six months, and often longer Patients with progressive infections are treated for years if not life-long. This can include IV amphotericin B as well as oral drugs. Some patients with meningitis receive amphotericin B by needle directly into the fluid around the brain several times a week for months or years. 11

12 Valley Fever Epidemiology Asymptomatic Symptomatic Valley Fever Epidemiology 150K 60K 22.4K 8.9K Unreported cases Reported cases Estimated US cases Symptomatic cases Do not Require Hospital -ization (some still Severe) Hospitalized (one or more days) Hospitalization status Complicated Primary, Short stay Reasons for hospitalization* High Unmet Need Target for New Therapies 40% unresponsive to current drugs Low side effects make 100% possible An estimated 150,000 people are infected with coccidioidomycosis annually in the US Endemic to southwestern deserts of the US with over 90% of cases in Arizona and California Additional populations in parts of Nevada, New Mexico, Utah, and west Texas The majority of infections are asymptomatic and people will not present with the condition An estimated 40% of people will develop pneumonialike symptoms which may progressively worsen Valley Fever is frequently undiagnosed or misdiagnosed due to nonspecific symptoms Patients with more severe symptoms or prolonged (> 1 week) respiratory infection may receive a serological test to confirm diagnosis CDC reports indicate 22.4k patients were diagnosed with Valley Fever in 2011; annual totals often vary between 15k and 25k Although diagnosed patients will frequently resolve with or without treatment, some 10-15% will develop severe complications, often requiring hospitalization Note: Based on Coccidioidomycosis-associated hospitalizations in the U.S. in , by ICD-9 code at discharge: (Primary Coccidioidomycosis), (Coccidioidal Meningitis), (Progressive Coccidioidomycosis), (Chronic Pulmonary Coccidioidomycosis), (Pulmonary Cocidioidomycosis NOS), (Coccidioidomycosis NOS) References: The New Yorker article, Emerging infectious diseases, CDC, HCUP, Valley Fever Solutions 12

13 Thank you! Improving the Standard of Care Nikkomycin Z Proof of Concept Summer