Coiled Therapeutics PLC · LSE:COIL
Coiled Therapeutics — Roquefort Investments — Merger or Acquisition (November 2021)
31 slides from Coiled Therapeutics's merger presentation, November 2021
Slide 1: Acquisition of Lyramid Limited
ACQUISITION OF LYRAMID LIMITED Midkine-Based Therapies for Treatment of COVID-19 Patients, Cancer, Chronic Inflammation & Autoimmune Disorders November 2021 www.roquefortinvest.com
Slide 2: Disclaimer
Disclaimer Investors Resident in the UK This Presentation is only being made available to the following in the United Kingdom: persons that are "qualified investors" within the meaning of Article 2(e) of Regulation (EU) 2017/1129 as it forms part of UK law by virtue of the European Union (Withdrawal
Slide 3: Corporate Overview
Corporate Overview Successful IPO in March 2021 • Roquefort Investments is listed on the LSE:ROQ • Experienced Board with proven track record in bringing companies to market and completing value accretive transactions • Raised £1 million in March 2021 IPO • Established to acquire an early stage busi
Slide 4: Board of Directors
Board of Directors Stephen West: Executive Chairman Dr Michael Stein: Non-Executive Director § over 26 years’ financial and corporate experience gained in § medical doctor (Honours) and biochemist (First Class public practice, oil and gas, mining and investment banking Honours) from the University o
Slide 5: Overview of LYRAMID Limited
Overview of LYRAMID Limited Licence holder of the largest global IP portfolio on Midkine • Patent portfolio covering composition of matter and method of use of Midkine inhibitors Novel disease target • Potential to exploit the broad therapeutic potential of Midkine for a number of clinical indicatio
Slide 6: Management Team
Management Team Graham Robertson: CSO Scientific Advisers § Associate Professor who gained his PhD in molecular virology before undertaking post- § International pioneer in ‘concept to doctoral training at Oxford patient’ development of oligonucleotide- § As group leader at the ANZAC and Garvan Inst
Slide 7: Midkine Research
Midkine Research Midkine: Novel Disease Target LUNG: RAAS – ANGIOTENSIN II • Midkine is a heparin binding growth factor NEUTROPHIL ACTIVATION CANCER IMMUNOTHERAPY RESISTANCE involved in many diseases - chronic inflammation, autoimmunity and cancer INFLAMMATORY TUMOUR RESPONSES METASTASIS • Prominent
Slide 8: Midkine-Based Therapeutics
Midkine-Based Therapeutics • Over A$40 million invested in licenced Midkine intellectual property portfolio • LYRAMID is now in the pre-clinical stages of developing first-in-class drugs targeting Midkine for treatment of many diseases with a focus on: – COVID-19 Patients – Cancer – Chronic inflamma
Slide 9: Business Model
Business Model RESEARCH PRE-CLINICAL PHASE I/II • Extensive research (10 • Design & testing of • Proposed rapid entry of years) identifies Midkine oligonucleotide drugs to block Midkine oligonucleotide as being involved in many Midkine drugs into the clinic diseases • Initial focus on COVID-19 and •
Slide 10: Midkine Program: Proposed Milestones
Midkine Program: Proposed Milestones MIDKINE OLIGONUCLEOTIDE (MK-ON) DRUG DEVELOPMENT 2021 2022 2023 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Collaboration Phosphoro- Oligonucleotide In vivo test In vivo test Scalable Good Investigational for MK- diamidate delivery vehicle inflammatory autoimmune Manufacturing New Drug
Slide 11: Market Potential
Market Potential PROPOSED FOCUS OF MIDKINE BLOCKING DRUG DEVELOPMENT COVID-19 Cancer Anti-Inflammatory Autoimmune US$25.6 US$75 US$98 US$110 Billion Billion Billion Billion COVID-19 Cancer Global anti- Autoimmune disease therapeutics market immunotherapy inflammatory therapeutics market expected to
Slide 12: Exit Potential
Exit Potential 2019 – 2020 Pharma Deals Acquiror/Partner Deal Upfront M&A Drug Target Disease (s) Stage ($B) ($M) licence J&J/Momenta 6.5 - M&A Nipocalimab Fc receptor Autoimmune Ph 2 Gilead/Forty Seven 4.9 - M&A Magrolimab CD47 Cancer Ph 1b Merck/VelosBio 2.75 - M&A VLS-101, conjugated ROR1- Cancer
Slide 13: Funding
Funding Equity Raise Proposed raising £3 million at a price of 10p per share Intended Use of Proceeds £’000 Acquisition consideration 500 Acquisition working capital adjustment 160 Midkine-blocking drug development 1,000 Contingency: other development work 500 Costs of RTO & fundraise 440 Working ca
Slide 14: Capital Structure
Capital Structure Cash Number % £’m SHARES Current Shares on Issue 0.90 36,900,000 51% LYRAMID Consideration (0.50) 5,000,000 7% £3 million Placing @ 10p+ 3.00 30,000,000 42% Costs+ (0.44) - - TOTAL 2.96 71,900,000 100% WARRANTS Warrants on issue pre-RTO (10p) 23,980,000 Deal origination warrants (1
Slide 15: Appendix - Midkine Research
APPENDIX - MIDKINE RESEARCH - Corporate Presentation – November 2021 Page 15
Slide 16: COVID-19 Patients
COVID-19 PATIENTS Corporate Presentation – November 2021 Page 16
Slide 17: COVID-19: Midkine Drug Development
COVID-19: Midkine Drug Development § Midkine levels are elevated in hospitalized COVID-19 patients (Unpublished data) providing support for the concept that Midkine impacts on progression of COVID-19 and associated multi-organ failure by: • Exacerbating the imbalanced RAAS that causes significant pa
Slide 18: COVID-19 and Midkine: SARS-CoV-2 Viral Entry & Lung Injury
COVID-19 and Midkine: SARS-CoV-2 Viral Entry & Lung Injury § Initial entry of SARS-CoV-2 into lungs is mediated by binding of the spike protein to Angiotensin Converting Enzyme 2 (ACE2) located on lung respiratory cells § Viral particle internalization depletes ACE2 alongside further reduction of AC
Slide 19: COVID-19: Infection & Pathology
COVID-19: Infection & Pathology • SARS-CoV-2 viruses first enter respiratory cells by attachment of viral spike protein to ACE2. • Imbalanced Renin-Angiotensin-Aldosterone-System (RAAS) due to reduced ACE2 and unfettered Angiotensin II action causes further collateral damage to lungs and other organ
Slide 20: COVID-19: Vascular Thrombosis
COVID-19: Vascular Thrombosis In lungs of COVID-19 patient, 80% of Healthy lung COVID-19 lung blood vessels are blocked compared to 22% in healthy lungs Medium = Open blood vessel = Blocked blood vessel Blood vessels Pulmonary Capillaries Open blood vessel Blocked blood vessel COVID-19 patients Norm
Slide 21: COVID-19: Midkine, inflammation & neutrophils
COVID-19: Midkine, inflammation & neutrophils § Midkine promotes recruitment of inflammatory cells such as neutrophils from the circulation into sites of tissue injury such as lungs § In autoimmune myocarditis Midkine antibody IP10 reduced infiltration into heart muscle of: LRP-1 LFA-1 • Neutrophils
Slide 22: Cancer
CANCER Corporate Presentation – November 2021 Page 22
Slide 23: Cancer: Midkine-Based Drugs
Cancer: Midkine-Based Drugs § Midkine is a growth factor/cytokine that is involved in most cancer types § Midkine contributes to critical tumour processes: • Rewiring the tumour immune microenvironment • Promoting immunotherapy resistance to Yervoy, Keytruda and Opdivo • Metastasis and lymphangiogen
Slide 24: Cancer: Example of Targeting Midkine on Tumour Growth
Cancer: Example of Targeting Midkine on Tumour Growth • Shortened form of Midkine protein (MDKD81-121) inhibits tumour cell proliferation while promoting apoptosis resulting in dramatic reduction in tumour growth Neuroblastoma xenograft model Full length MDK Full length MDK Tumour volume MDKD81-121
Slide 25: Cancer: Midkine Causes Resistance to Immunotherapy Drugs
Cancer: Midkine Causes Resistance to Immunotherapy Drugs § Midkine’s immunomodulatory actions: • disrupt macrophage and T cell CHECKPOINT INHIBITOR functions, thereby promoting immune SENSITIVE RESISTANT evasion in melanoma • drive resistance to immune checkpoint inhibitors Keytruda and Opdivo • onl
Slide 26: Cancer: Midkine & Melanoma Metastasis
Cancer: Midkine & Melanoma Metastasis Midkine Tumour-derived Midkine (MDK) promotes lymphangiogenesis and metastasis in distal sites such as the lung independent of localized lymph vessels adjacent to the Kaplan-Meier survival analysis shows melanoma patients with high levels of midkine (MK) in sent
Slide 27: Cancer: Midkine Signalling Promotes Glioma
Cancer: Midkine Signalling Promotes Glioma Guo X et al 2020, Nature Communications 11:2177 Midkine Ø RAS promotes production of Midkine (MDK) in NF1 mutant neurons Ø Neuron-derived midkine drives chemokine CCL4 release from CD8+ T cells Midkine Ø CCL4 elicits CCL5 signalling by MDK microglia to supp
Slide 28: Chronic Inflammation & Autoimmune Disorders
CHRONIC INFLAMMATION & AUTOIMMUNE DISORDERS Corporate Presentation – November 2021 Page 28
Slide 29: Chronic Inflammation and Autoimmune Disorders: Midkine-Based Drugs
Chronic inflammation and Autoimmune Disorders: Midkine-Based Drugs Blocking Midkine activity via MK gene silencing, therapeutic antibodies or with MK gene knockouts improves disease and preserves organ function via multiple important mechanisms: § Reduced leukocyte recruitment to the sites of inflam
Slide 30: Chronic Inflammation and Autoimmune Disorders: Midkine-Based Drugs
Chronic inflammation and Autoimmune Disorders: Midkine-Based Drugs The therapeutic efficacy of blocking Midkine has been demonstrated in multiple in vivo models of: Ø Renal Diseases Ø Autoimmune disorders Ø Chronic inflammatory heart failure Ø Neurodegenerative disease Ø Lung disease/ARDS Ø Fibrosis
Slide 31: Big results require big ambitions
www.roquefortinvest.com “Big results require big ambitions” Heraclitus
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