SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, DC 20549
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of report (Date of earliest event reported): March 23, 2021
ANNOVIS BIO, INC.
(Exact Name of Registrant as Specified in Charter)
(State or Other Jurisdiction
1055 Westlakes Drive, Suite 300
Berwyn, PA 19312
(Address of Principal Executive Offices, and Zip Code)
Registrant’s Telephone Number, Including Area Code
(Former Name or Former Address, if Changed Since Last Report)
Securities registered pursuant to Section 12(b) of the Act:
|Title of each class||Trading Symbol(s)||
Name of each exchange on which
Common Stock, par value $0.0001 per
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 (see General Instruction A.2. below):
|¨||Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425)|
|¨||Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)|
|¨||Pre-commencement communication pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))|
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. x
|Item 7.01||Regulation FD Disclosure.|
On March 24, 2021, as part of the Q1 Investor Summit, Chief Executive Officer Maria Maccecchini, Ph.D., and Chief Financial Officer Jeff McGroarty, MBA, CPA, will give a presentation via webcast at 11:30 a.m. Eastern Time, followed by a live Q&A session. A copy of the written presentation materials is attached as Exhibit 99.1 to this Current Report on Form 8-K. A copy of the presentation is also available on the Company’s website at www.annovisbio.com under “Investors & Media.” Investors can register for and access the live webcast at: https://zoom.us/webinar/register/WN_LKCiDrrKROa4nLfrPKSiAA
The information in this Item 7.01, including the attached exhibit, is furnished solely pursuant to Item 7.01 of Form 8-K. Consequently, such information is not deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, or otherwise subject to the liabilities of that section. Further, the information in this Item 7.01, including the exhibit, shall not be deemed to be incorporated by reference into the filings of the registrant under the Securities Act of 1933.
Cautionary Statement Regarding Forward-Looking Information
This current report on Form 8-K contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than those of historical fact in this presentation and accompanying oral commentary are forward-looking statements. Forward-looking statements may be identified by terminology such as “believe,” “anticipate,” “plan,” “may,” “intend,” “will,” “should,” “expect,” “estimate,” “potential” and “continue” and similar expressions, including the negative of these words, but not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements regarding the Company’s expectations regarding projected timelines of clinical trials, and expectations regarding current or future clinical trials. Forward-looking statements are based on the Company’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate, including the timing of clinical trials. These and other risks and uncertainties are described more fully in the section titled “Risk Factors” in the Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission (“SEC”) and elsewhere in our filings and reports with the SEC. These risks, uncertainties and other factors may cause our actual results to differ materially and adversely from what is contained in (or may be implied from) any forward-looking statements. Forward-looking statements speak as of the date they are made, and the Company undertakes no obligation to update them except as may be required under applicable law.
|Item 9.01||Financial Statements and Exhibits.|
|99.1||Presentation dated March 2021 (furnished herewith)|
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.
|ANNOVIS BIO, INC.|
|Date: March 23, 2021||By:||/s/ Jeffrey McGroarty|
|Name: Jeffrey McGroarty|
|Title: Chief Financial Officer|
Attacks Alzheimer’s Disease and Neurodegeneration by Improving the Information Highway of the Nerve Cell Axonal Transport March 2021 Symbol: ANVS (NYSE American)
FORWARD - LOOKING STATEMENTS Statements in this presentation contain “forward - looking statements” that are subject to substantial risks and uncertainties. Forward - looking statements contained in this presentation may be identified by the use of words such as “anticipate,” “expect,” “believe,” “will,” “may,” “should,” “estimate,” “project,” “outlook,” “forecast” or other similar words, and include, without limitation, statements regarding Annovis Bio, Inc.’s expectations regarding projected timelines of clinical trials, and expectations regarding current or future clinical trials. Forward - looking statements are based on Annovis Bio, Inc.’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward - looking statements are based on assumptions as to future events that may not prove to be accurate , including the timing of clinical trials . These and other risks and uncertainties are described more fully in the section titled “Risk Factors” in the Annual Report on Form 10 - K for the year ended December 31, 2020 filed with the Securities and Exchange Commission. Forward - looking statements contained in this presentation are made as of this date, and Annovis Bio, Inc. undertakes no duty to update such information except as required under applicable law. 2
3 ▪ Annovis is developing drugs for Alzheimer's (AD) and Parkinson's disease (PD), including the orphan indication Alzheimer's in Down Syndrome (AD - DS) ▪ Lead compound, ANVS401, is the only drug to improve axonal transport, the information highway of the nerve cell, by attacking multiple neurotoxic proteins ▪ Two phase 2a clinical trials: ▪ AD trial run by Alzheimer’s Disease Cooperative Study (ADCS) ▪ AD and PD trial ▪ Successful completion of phase 2a clinical trials will validate our approach and allow start of two phase 3 studies HIGHLIGHTS A novel approach to treat neurodegeneration is desperately needed
THE STATE OF NEURODEGENERATIVE DISEASES ▪ 5.8 million people in the US and 44 million people worldwide are estimated to suffer from AD ▪ PD affects an estimated one million people in the U.S. and as many as 10 million globally ▪ Total costs of care for people with Alzheimer’s and other dementias could top $1.1 trillion in 2050 ▪ From 1998 to 2018 there were over 500 failed attempts at developing Alzheimer's drugs, primarily focused on amyloid plaque ▪ The sector needs to rethink dementia, develop new approaches and create new drugs 4
CHANGE IN CAUSES OF DEATH FROM 2000 TO 2018 5 • Breast Cancer - 13% • Colon Cancer - 21% • Heart Disease - 21% • Stroke - 24% • HIV - 67% • Parkinson’s + 84% • Alzheimer’s + 112%
Chronic and acute brain insults lead to high levels of neurotoxic proteins, to inflammation and neurodegeneration Attacking one neurotoxic protein results in minimal effect ANVS401 is the only drug to attack multiple neurotoxic proteins simultaneously Amyloid β AD / PD - A β Targeting Compounds ANNOVIS’ DRUG ATTACKS MULTIPLE NEUROTOXIC PROTEINS Tau Tauopathies - AD - Tau Targeting Compounds aSynuclein PD / AD - aSYN Targeting Compounds 6 Activated Microglia = High Inflammation
PIPELINE 7 Therapy Diseases/Conditions PRE - CLINICAL IND PHASE I PHASE II PHASE III AD PD AD - DS FTD CTE TBI Stroke Advanced AD Oral drug for chronic indications Injectable drug for acute traumatic events Oral drug for advanced AD and dementia
8 CORPORATE PATENT ESTATE Patent/Application Subject Matter Status Expiry Provisional ANVS401 to treat viral and bacterial infections of the brain, including Covid19 Pending 2041 PCT ANVS401 and 405 – Mechanism of Action for prevention and treatment of diseases Pending 2038 PCT ANVS405 - Acute brain and nerve injuries EP 3334425B1; 12 - 2020 2036 PCT ANVS401 - pK/pD, low doses , formulations Neurodegenerative Diseases US 10,383,851; 07 - 2019 EP 2683242; 03 - 2020 2031 In - licensed patents Composition of matter, manufacturing, method for treating AD and DS Granted 2022 - 25 Composition of Matter and Method of Use Process for Production Methods of Use: pK/pD, Dose, Formulations Method of Use: Acute Brain and Nerve Injuries Method of Use: Prevention and Treatment Multi - layer strategy
NEUROTRANSITTERS THAT TRAVEL ACCROSS THE AXON Adrenaline Noradrenaline Dopamine HOW NERVE CELLS WORK In healthy nerve cells little packages containing neurotransmitters or nerve growth factors travel unimpaired from the cell body through the axon to the synapse. SOMA & CELL BODY DENDRITES Serotonin Gaba Acetylcholine Glutamine Endorphins SYNAPSE 9 Neurotoxic proteins limit the flow and speed at which neurotransmitters travel along the axon resulting in compromised nerve function THE INFORMATION HIGHWAY
NEUROTOXIC PROTEINS IMPAIR AXONAL TRANSPORT AND CAUSE A TOXIC CASCADE ANVS401 IMPROVES AXONAL TRANSPORT AND IMPEDES THE TOXIC CASCADE IMPAIRED AXONAL TRANSPORT SLOWER SYNAPTIC TRANSMISSION INFLAMMATION DEATH OF NERVE CELLS LOSS OF COGNITIVE AND MOTOR FUNCTION IMPROVED AXONAL TRANSPORT INCREASED SYNAPTIC TRANSMISSION NO INFLAMMATION HEALTHY NERVE CELLS IMPROVED COGNITIVE AND MOTOR FUNCTION HIGH LEVELS OF NEUROTOXIC PROTEINS ANVS401 LOWERS LEVELS OF NEUROTOXIC PROTEINS
11 RESULTS IN HUMANS ANVS401 Lowers Neurotoxic Proteins in Cerebrospinal Fluid (CSF) of Mild Cognitive Impaired (MCI) Patients ▪ In this proof - of - concept study, ANVS401 lowers the levels of APP/Aβ, tau/p - tau and αSYN back to the levels seen in healthy volunteers ▪ It lowers the levels of the three neurotoxic proteins causing AD and PD Maccecchini et al: JNNP 2012; 83: 894 - 902
NEURODEGENERATION IS AN AXONAL TRANSPORT DISEASE Axonal transport is responsible for: Normal Transport The Normal Flow and Speed of vesicles carrying BDNF across the axon. ▪ Neurotransmitters GABA (anxiety), ACh (cognition), dopamine (movement), serotonin (mood) ▪ Neurotrophic factors NGF, BDNF ▪ All communication within and between nerve cells “ Axonal transport disruption is linked to human neurological conditions. ” - Nature Review, September 2019 Abnormal Transport Shows the Blockage and Slowing of BDNF across the axon. Black areas demonstrate where transport is slowed due to high levels of neurotoxic proteins. TREATED WITH The Flow and Speed of axonal transport is improved. (120s) (88s) (88s) APP, Ab42, C99 – Mobley, UCSD; aSYN – Isacson, Harvard; Lee, U.Penn; Tau – U. Muenich & Zuerich; Htt – Mobley, UCSD; TDP43 – Taylor, Northwestern Retrograde (0.5 frame/sec) 12
13 ANVS401 LOWERS INFLAMMATORY MARKERS Maccecchini et al: JNNP 2012; 83: 894 - 902 CSF Inflammatory Markers Significantly Decrease After 10 Days of Oral ANVS401 in MCI Patients Inflammatory Protein CSF % of Baseline p - Value Complement C3 - 86.9% 0.0007 MCP - 1 - 87.5% 0.0007 YKL40 - 72.7% 0.0113 sCD14 - 26.1% 0.1159 Factor FH* 23.7% 0.4988 * Control Factor
14 RESULTS IN ANIMALS Multiple animal studies showed that ANVS401 improved the affected function Function Animal Model Memory and learning AD mice, DS mice, stroke mice, TBI rats Movement PD mice, FTD mice Eyesight Acute glaucoma rats
15 TWO PHASE 2 CLINICAL TRIALS AD Trial AD / PD Trial CRO ADCS Parexel Therapeutic Area Early AD Early to Moderate AD and PD Phase 2 2 Patients 24 28 + 40 Sites 6 12 Country United States Design Double - Blind, Placebo - Controlled, Biomarker Study Endpoints Reversal of Toxic Cascade
PHASE 2 CLINICAL TRIAL IN AD AND PD TO MEASURE REVERSAL OF THE TOXIC CASCADE AND IMPROVEMENT IN BRAIN FUNCTION DECREASE IN NEUROTOXIC PROTEINS INCREASE IN NEUROTRANSMITTERS LOWERING OF INFLAMMATORY PROTEINS LOWERING OF NEURODEGENERATION MARKERS COGNITION AND MOTOR FUNCTION ENDPOINTS TARGET: PATHWAY: EFFICACY:
TIMELINE OF PHASE 2 CLINICAL TRIAL IN AD and PD Preliminary data to be available beginning in 1Q2021 Start Up AD/PD Study August 2020 May 2021 June 2021 17 A meeting with the FDA to discuss the data from the AD and the PD study as well as from the chronic toxicology in rats and dogs is projected for Fall of 2021 14 AD 14 PD 68 Patients March 2021
EFFICACY IN PD PATIENTS – SPEED & COORDINATION Preliminary data from first 14 PD patients 30 35 40 45 50 55 0 25 BASELINE VS 25 DAYS 30 35 40 45 50 55 PLACEBO ANVS401 PLACEBO VS 401 0 0.5 1 1.5 2 2.5 3 0 25 Baseline vs 25 Days 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 placebo ANVS401 Placebo vs 401 Speed: Left the comparison between the treated group with 80 mg/day of ANVS401 at baseline before treatment and after 25 days on treatment in the rapid coding test. At 25 days the speed is faster than at baseline and they make fewer mistakes (p<0.04). Right the comparison between the placebo group and the treated group at 25 days. This graph shows that while the placebo group gets slower, the treated group gets faster (p< 0.04). The lower number shows worse performance. 18 Coordination : Left - Comparison between treated at baseline and at 25 days. The two scores are identical – patients remain stable Right, the comparison is made between the placebo group and the treated group both at 25 days. The placebo treated group shows a marked deterioration in their motor complications compared to the ANVS401 treated group that was stable (p< 0.07). The lower number shows better performance.
REVERSAL OF TOXIC CASCADE EXPECTED OUTCOME ACTUAL OUTCOME Level of neurotoxic proteins Axonal transport Inflammation Dead nerve cells Control proteins 0 Efficacy: Motor function + Efficacy: Cognition REVERSAL OF TOXIC CASCADE Preliminary data from first 14 PD patients 19 +++ p < 0.001 0 no change ++ p < 0.01 - Opposite result from expected + p < 0.05 +/ - trend All rows for Parkinson’s disease will read out later and the same outcomes will also read out for Alzheimer’s disease
1% 2% 4% 8% 16% 47% 60-65 65-70 70-75 75-80 80-85 85+ 20 MARKET PROJECTIONS Source: Alzheimer‘s Association 2014; Incidence of AD in Relation to Age Increase in Incidence with Aging of Population Annual sales potential for US and worldwide are over $100 billion dollars
FINANCIAL HIGHLIGHTS 21 ▪ Completed IPO in January 2020 ▪ Cash balance provides runway to end of 2021 ▪ NIH grants funding ADCS Phase 2a trial in AD and chronic toxicology study ▪ ~40% insider ownership ▪ Analyst coverage from ThinkEquity and Maxim Group Ticker NYSE American: ANVS Recent Price $25.57 52 - Week Range $2.42 - $35.00 Market Cap $176.6M Shares Outstanding 6.9M Float 4.4M Cash (mrq) $8.8M LT Debt (mrq) $0.0M KEY DATA Share price and market cap as of February 26, 2021
CHIEF EXECUTIVES AND CHIEF ADVISORS Jeffrey Cummings, MD, Chief Medical Advisor Dr . Cummings completed Neurology residency and a Fellowship in Behavioral Neurology at Boston University, Boston, Massachusetts . US training was followed by a Research Fellowship in Neuropathology and Neuropsychiatry at the National Hospital for Nervous Diseases, Queen Square, London, England . Dr . Cummings was formerly Professor of Neurology and Psychiatry at UCLA, director of the Mary S . Easton Center for Alzheimer’s Disease Research at UCLA, director of the Deane F . Johnson Center for Neurotherapeutics at UCLA and director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Cleveland and Florida . He is past president of the Behavioral Neurology Society and of the American Neuropsychiatric Association . Dr . Cummings has authored or edited 30 books and published nearly 600 peer - reviewed papers . 22 Maria L . Maccecchini, PhD Founder, President & CEO Founded Annovis in May 2008 to develop better therapeutics for Alzheimer’s, Parkinson’s and other neurodegenerative diseases . Was partner and director of two angel groups, Robin Hood Ventures and MidAtlantic Angel Group ; Founder and CEO of Symphony Pharmaceuticals/Annovis a biotech company that sold in 2001 to Transgenomic ; General Manager of Bachem Bioscience, the US subsidiary of Bachem AG, Switzerland and Head Molecular Biology Mallinckrodt ; Dr . Maccecchini did one postdoc at Caltech and one at the Roche Institute of Immunology, her PhD in biochemistry is from the Biocenter of Basel with a two - year visiting fellowship at The Rockefeller University . Jeffrey McGroarty, CPA, MBA, Chief Financial Officer Jeff is a financial executive with experience in investor relations, working with analysts, creditors and financial institutions, planning and analysis, capital allocation, SEC communications and reporting, accounting, acquisitions and turnarounds . He is experienced in effectively managing complex projects, building professional relations and developing staff . Mr . McGroarty was previously employed as CFO of Safeguard Scientifics, Interim Controller at Cephalon, Inc . , Vice President - Financial Planning and Analysis of Exide Technologies, Inc . , and Senior Manager at PWC . Jeff’s MBA is from the Wharton School of Business . William Mobley, MD, PhD Chief Scientific Advisor Distinguished Professor, Department of Neurosciences Florence Riford Chair for Alzheimer Research and Associate Dean for Neurosciences Initiatives at UC San Diego . He is a member of the National Academy of Medicine . His research focuses on the neurobiology of neurotrophic factor actions/signaling and on the hypothesis that malfunction of these mechanisms contribute to neuronal dysfunction in developmental and age - related disorders of the neurosystem .
SCIENTIFIC ADVISORY BOARD 23 Sidney Strickland, PhD, Chairman Vice President and Dean for Educational Affairs and Research Professor, Patricia and John Rosenwald Laboratory of Neurobiology and Genetics at Rockefeller University. Dr. Strickland’s laboratory investigates how dysfunction of the circulatory system contributes to Alzheimer’s and other neurodegenerative disorders. He will serve as the Chairman of Annovis Bio’s SAB. Jeffrey Cummings, MD Dr . Cummings completed Neurology residency and a Fellowship in Behavioral Neurology at Boston University, Massachusetts . US training was followed by a Research Fellowship in Neuropathology and Neuropsychiatry at the National Hospital for Nervous Diseases, London, England . Dr . Cummings was formerly Professor of Neurology and Psychiatry, Director of Alzheimer’s Disease Research and Director of the Center for Neurotherapeutics at UCLA . He was Director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Cleveland and Florida . William Mobley, MD, PhD Dr . Mobley is Distinguished Professor, Department of Neurosciences Florence Riford Chair for Alzheimer Research and Associate Dean for Neurosciences Initiatives at UC San Diego . He is a member of the National Academy of Medicine . His research focuses on the neurobiology of neurotrophic factor actions/signaling and on the hypothesis that malfunction of these mechanisms contribute to neuronal dysfunction in developmental and age - related disorders of the neurosystem . Gregory Petsko, PhD He is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences and the American Philosophical Society . His research interests are directed towards understanding the biochemical bases of neurological diseases like Alzheimer’s, Parkinson’s, and ALS discovering treatments (especially by using structure - based drug design), that could therapeutically affect those biochemical targets, and seeing any resulting drug candidates tested in humans . He has also made key contributions to the field of protein crystallography . Rudolph E. Tanzi, PhD Dr . Tanzi has published over 500 research papers and has received the highest awards in his field, including the Metropolitan Life Foundation Award, Potamkin Prize, Ronald Reagan Award, Silver Innovator Award, and many others . He was named to TIME magazine’s list of TIME 100 Most Influential People in the World ( 2015 ), and received the Smithsonian American Ingenuity Award, the top national award for invention and innovation . He co - authored the popular trade books “Decoding Darkness”, New York Times bestseller, “Super Brain”, and international bestseller “Super Genes” .
24 Michael B . Hoffman Chairman Mr . Hoffman is the Founder and Managing Partner of Stone Capital Partners, a private equity firm focused on power and renewable energy . He was Partner of Riverstone, senior managing director at the Blackstone Group and managing director at Smith Barney, Harris Upham & Co . He serves as Chairman of Onconova, Annovis Bio, Curative and is on the Board of Rockefeller University . Claudine E . Bruck, PhD Pharmaceutical executive and scientist with strong entrepreneurial drive . Exhibited successes in building a therapeutic research unit de novo and leading discovery and clinical development of biological (vaccines, biopharmaceuticals) and small molecule medicines as well as an ophthalmic drug portfolio . With creativity and a strong results - focus, she is energized to challenge and lead teams . Extensive Pharmaceutical industry experience spans drug discovery and development across several therapeutic areas . Mark White Mark is a biopharmaceutical executive with global marketing, business development and sales experience . Currently, Mark is an independent consultant and a member of Robin Hood Ventures, a Philadelphia based angel investor group . Previously, Mark held senior level roles at Pfizer in marketing and commercial development, where he led the successful global launches of Inspira, Revatio, Lyrica and Xeljanz . In his last position, he was Vice President Worldwide Marketing, with global responsibility for new product development and in - line marketing for Pfizer’s Inflammation Therapeutic Area . Maria L. Maccecchini, PhD Executive Board Member Founded Annovis in May 2008 to develop better therapeutics for Alzheimer’s, Parkinson’s and other neurodegenerative diseases . Founder and CEO of Symphony Pharmaceuticals/Annovis focused on protecting brain cells after stroke . It sold in 2001 to Transgenomic . BOARD OF DIRECTORS
INVESTMENT SUMMARY A novel approach to treat neurodegeneration is desperately needed ▪ The markets for AD and PD drugs are in the multibillions of dollars and growing ▪ Annovis has a novel approach to stop the course of AD and PD ▪ ANVS401 improves axonal transport and recovers the affected function ▪ The successful completion of our Phase 2 clinical trials will provide validation of our approach in two diseases and allow us to move to Phase 3 trials 25
Improves THE FLOW of Axonal Transport in Alzheimer’s Disease and Neurodegeneration CONTACT US 1055 Westlakes Drive Suite 300 Berwyn, PA 19312 +1 (610) 727 - 3913 email@example.com Investor Relations Dave Gentry CEO, RedChip Companies +1 (407) 491 - 4498 firstname.lastname@example.org www.annovisbio.com Symbol: ANVS (NYSE American)