Developing Novel Treatments for Autoimmune Diseases

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1 ACCELERATED PATH TO CURES Developing Novel Treatments for Autoimmune Diseases

2 Landos Strengths Scientific, Clinical and Business Leadership 2 Expandable Oral Therapeutic Pipeline Financially Stable Raised $10M Series A to advance Lead to Phase 1; Landos will be raising $30-50M Series B for Phase 2 TECHNOLOGY First-in-class oral therapeutics with a unique MoA targeting LANCL2 Advancing Lead Candidate in Crohn s and Ulcerative colitis Product Development Validation Successful PreIND for BT-11 & Open IND for BT-11 Strong animal pharmacology in 5 IBD models, toxicology and human translation Phase 1 First in Man testing underway Strong IP Comp of Matter and Method of Use, Long patent life 2035 Possible Exit Strategy IPO, M&A or Strategic Alliance at the end of Ph. 2

3 Crohn s Disease and Ulcerative Colitis IBD afflicts 2 million in the U.S. and 5 million people worldwide 5M afflicted $10B market 25% growth 70-90% will require surgery 100,000 hospitalizations 3

4 The IBD Market: $10B 25% Growth Autoimmune disease therapeutics market in U.S. is $100 billion Biologics (68%) Others (5%) 4 Immunomodulators (19%) 5 ASA (8%) Biological treatment dominates most of the market share. However, it is expected to drop 11 points, down to 57%, by 2026 due to safety concerns and emerging novel technologies with significant competitive advantages

5 Unique MOA: Lanthionine Synthetase C-Like 2 HOW LANCL2 WORKS BT-11 LANCL2 AC PKA CREB 5 5 AMP camp LANCL2 activation by BT-11 intercepts IBD at two levels: by decreasing the production of inflammatory mediators (TNF, IFNg, MCP1) and increasing antiinflammatory molecules (IL-10, FOXP3) in the GI tract. First in class compounds with oral ROA and local GI action ATP BT-11, 48 scaffolds, and 3 billion NCEs composition of matter claims allowed in USPT 9,556,146; 2017 & 9,839,635 in 2018; 15 countries Activates IL-10 & FOXP3 Both method of use and composition of matter claims for IBD, RA, T1D, T2D, and influenza Inhibits TNF- & IFN-g

6 Expansible Therapeutic Pipeline Product Indication BT-11 CD BT-11 UC NX-13 UC/CD BT-63 T1D BT-63 T2D INT10 CDI BT-110 Flu BT-13 RA Preclinical POC Preclinical INDenabling 6 Phase I Phase II *

7 BT-11 Target Product Profile For CD & UC Product Name Prime Therapeutic Indications BT-11 First: Treatment for alleviation of signs and symptoms and induction and maintenance of clinical remission in male and female adult patients with moderate to severe CD. Second: Treatment for alleviation of signs and symptoms and induction and maintenance of clinical remission in male and female adult patients with mild to moderate UC. 7 Lead Competitor (TNF- blockers) Treatment to reduce signs and symptoms and induce and maintain remission in adult patients with moderate to severe CD or UC who have not responded to other therapies. ROA/Dosage Oral once-a-day dosing through a tablet until symptoms alleviate (8 mg/kg in mouse models) I.V. infusion Formulation Tablets (Phase 1 & 2) Sterile powder for I.V. infusion Activation of the LANCL2 pathway Neutralization of TNF- Mechanism of Up-regulation = IL-10, FOXP3 Action Down-regulation = TNF-, IFNg, MCP-1, IL-6 Efficacy Safety/ Tolerability Efficacy in 5 validated mouse models (8 mg/kg) Variable degrees of efficacy in 3 mouse models Benign safety profile up to 1,000 mg/kg p.o. in dogs and rats without dose-limiting safety issues. Increased risk for cancer (T cell lymphoma), infection and death

8 Efficacy Of BT-11 In 5 Validated Mouse Models Of IBD Untreated : Inflamed BT-11 Treated : Not Inflamed Oral BT-11 decreases gut inflammation by 90%, triggers 4x lesion reduction, and modulates inflammatory responses by up-regulating IL-10 and down-regulating TNF-a 8

9 BT-11 Targets LANCL2 In The GI Tract 9 Cmax = 28ng/mL t1/2 = 3.1hr Kel = L/hr Vd = 3.38 L/kg BT-11 systemic absorption is extremely low No dose proportionality (80 to 500 mg/kg) Limited systemic exposure No accumulation in plasma Volume of distribution is high BT-11 in the colon and colonic contents is high 90% reduction of inflammation BT-11 is stable to stomach and intestinal fluids

10 Oral Route Of Administration In support of it local action in the GI tract, oral and rectal BT-11 administration protects from IBD, but I.V. administration of BT-11 fails to protect from IBD. 10

11 Human Translational Data Treating human PBMCs from Crohn s disease patients with increasing concentrations of BT-11 ex vivo induced IL-10 production and expression of FOXP3 while suppressing production of TNF and IFNg 11

12 BT-11 Outperforms Current Drugs and INDs 12

13 BT-11 Has Demonstrated Benign Safety Profile BT-11 is negative in genotoxicity studies such as the Ames test up to 5,000 µg/plate; herg screening Single medium/high dose in rats (0 or 500 mg/kg) 7-day assessment & recovery. Multiple Moderate dose in rats (0 or 80 mg/kg) 14-day assessment & recovery DRF Studies in rats and dogs (0, 250, 500, and 1,000 mg/kg) 7-day assessment & recovery and safety pharmacology 28-day tox assessment & recovery in male and female rats (1,000 mg/kg) GLP 12-week assessment & 2 week recovery in rats (complete) and dogs (ongoing); 9 and 6 month dosing to support continuous dosing of BT-11 (post-ind). No dose-limiting safety issues. 13

14 Landos Has an Open IND for BT-11 UC IND Landos received Study May Proceed Notification for Phase 1 from the FDA on June 15, 2018 First-in-Humans Phase 1 Study Initiated in July,

15 Phase 1: Safety and Tolerability Single Ascending Dose Multiple Ascending Dose 7 day, once daily BT-11 : mg/kg Cohort 1 6 active, 2 placebo BT-11 : mg/kg Cohort 2 6 active, 2 placebo BT-11 : mg/kg Cohort 3 6 active, 2 placebo BT-11 : mg/kg Cohort 1 8 active, 2 placebo BT-11 : mg/kg Cohort 2 8 active, 2 placebo BT-11 : mg/kg Cohort 4 6 active, 2 placebo BT-11 : mg/kg Cohort 5 6 active, 2 placebo BT-11 : mg/kg Cohort 3 8 active, 2 placebo Double-blind, placebo-controlled study in male and female normal healthy volunteers under U.S. IND

16 BT-11 May Disrupt The IBD Rx Paradigm Our data indicate that BT-11 could be steroid-, biologicsand even surgery-sparing 5 ASA 6 MP Immunosuppresant TNFα blockers BT-11 / LANDOS technology Corticosteroids α4b7 blockers Surgery Current therapies are modestly successful with undesired side effects 16

17 Go-To-Market Timeline 2017 IND Enabling Series A $10M 2018 File INDs 2019 Phase 1 Series B $31-52M Phase 2a Phase 2b IPO $200M Phase NDA

18 Leadership Team Josep Bassaganya-Riera Chairman and CEO 20 years of business development and fundraising experience in leading biotech companies with innovative, large-scale translational programs. Preclinical and clinical expertise in Crohn s disease and ulcerative colitis. Has led large preclinical and clinical programs in IBD (>$78M). Raquel Hontecillas Chief Scientific Officer 20 years of translational experience in the biotech industry focusing on infectious, immune-mediated, and metabolic diseases. Managed an NIH-funded mucosal immunology program totaling $57M. 18 Chris Garabedian Corporate Advisor Currently Chairman and CEO of Xontogeny, a company focused on the management of early stage life sciences companies from preclinical to clinical proof-of-concept. Helped advance a new drug to market when he was the CEO of Sarepta a $4B publicly traded company. Simon J. Tulloch, MD Senior Clinical Advisor 25 years of pharmaceutical and biotech experience in strategic business development, clinical development and R&D management, both in Europe and the USA. Secured a $200 million R&D budget and grew the core business from $700 million to $1 billion at Shire Pharmaceuticals; served as CMO of InfaCare, with successful Series A, B, and C fund raising. He played a crucial role in NDA and taking Adderall to market. He has been involved in filing over 17 INDs and several NDAs.

19 Clinical Advisory Board - IBD 19 FABIO COMINELLI, MD, PHD Crohn s Disease Human Clinical Trials WILLIAM SANDBORN, MD Crohn s Disease Human Clinical Trials Director of the UH Case Medical Center, Cleveland. 20 years of experience with human clinical trials for new therapeutics in Inflammatory Bowel Disease. Chief, Division of Gastroenterology and Professor of Medicine at UC San Diego Health. He has over 20 years of experience with human clinical trials for new Inflammatory Bowel Disease (IBD) therapeutics. FRANCISCO A. SYLVESTER, MD Pediatric IBD JEAN-FREDERIC COLOMBEL, MD Preclinical and Clinical Gastroenterology Division Chief for Pediatric Gastroenterology at UNC Chapel Hill and member of the CCFA Board of Trustees. Over 25 years of experience in chronic inflammatory diseases. Director of the Helmsley IBD Center at Mount Sinai, NYC. 20 years of experience in Crohn s disease. Chair of the International Organization of Inflammatory Bowel Disease (IOIBD). MARIA T. ABREU, MD Preclinical and Clinical Gastroenterology Faculty of University of Miami Health System. Over 15 years of experience in IBD, specializing in mucosa and associated intestinal microbiota and expertise in preclinical models and clinical studies.

20 Financing Series B Scenarios ( ) OPTION A: 51.2M Dual UC & CD Phase 2 2 New Assets to IND 5% OPTION B: 37.2M Only UC Phase 2 2 New Assets to IND 8% 7% 8% 8% 34% 13% 10% OPTION C: 30.9M Only UC Phase 2 6% 5% 20 40% 11% 49% 9% 10% 15% 13% 13% 17% Phase 2 Clinical Trials Legal, Insurance and Operating Costs Employees and Consultants CMC Mfg IND Enabling Studies Chronic Studies Discovery Studies 18%

21 Phase 2 Exit Comparables Plexxikon: Daiichi Sankyo $835M upfront with $130M in milestones (SMALL MOLECULE) Nogra Pharma: Celgene acquired Mongersen (GED0301) for $710M upfront with $1.9B in development and sales milestones (ORALLY ACTIVE AND LOCALLY ACTING SMALL MOLECULE) Protagonist: J&J commits $990M for an oral Crohn s drug PTG-200 targets IL-23 receptor (ORAL PEPTIDE THERAPEUTIC) Theravance: J&J launched a $1B partnership on the pan-jak inhibitor (TD1473) with $100M cash upfront in a milestone-driven deal (ORALLY ACTIVE AND LOCALLY ACTING SMALL MOLECULE) 21

22 Summary and Conclusions Open IND June 2018 Begin Ph 2 clinical testing by Q Initiated Ph 1 human clinical testing July 2018 IPO by Landos is uniquely positioned to develop oral, firstin-class IBD therapeutics, a $10 billion market. Innovative MoA (LANCL2) with strong IP protection (NCEs & target). Strong animal pharmacology, MoA, toxicology, and translational data. Committed leadership with autoimmune disease and biopharma industry experience ready to execute therapeutic development plans. Partnering with Xontogeny for incremental operational expertise and access to talent. Seeking $31-52M for Series B financing.

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