Corporate Presentation

Transcription

1 Corporate Presentation

2 Disclaimer Statements in this presentation that are not descriptions of historical facts are forward looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of We have attempted to identify forward looking statements by terminology including anticipates, believes, can, continue, could, estimates, expects, intends, may, plans, potential, predicts, should, or will or the negative of these terms or other comparable terminology. Forward looking statements are based on management s current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are risks relating to: results of research and development activities; uncertainties relating to preclinical and clinical testing; our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; our dependence on third party suppliers; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; our ability to attract, integrate, and retain key personnel; the early stage of products under development; our need for substantial funds; government regulation; patent and intellectual property matters; and competition. We expressly disclaim any obligation or undertaking to update or revise any statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances after the date of this presentation. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, achievements or events and circumstances reflected in the forward-looking statements will occur. We are under no duty to update any of these forward-looking statements after the date of this presentation to conform these statements to actual results or revised expectations, except as required by law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation. Moreover, except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements contained in this presentation. By attending or receiving this presentation you acknowledge that you will be solely responsible for your own assessment of the market and our market position and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of our business. This presentation is made pursuant to Section 5(d) of the Securities Act of 1933, as amended, and is intended solely for investors that are qualified institutional buyers solely for the purposes of familiarizing such investors with Caelum Biosciences, Inc. and determining whether such investors might have an interest in a securities offering contemplated by Caelum Biosciences, Inc. Any such offering of securities will only be made by means of a registration statement (including a prospectus) filed with the SEC, after such registration statement becomes effective. No such registration statement has been filed, or become effective, as of the date of this presentation. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. 1

3 Caelum Biosciences is a biopharmaceutical company focused on treatments for rare hematologic diseases Lead candidate CAEL-101 is a first-in-class anti-amyloid antibody for treating AL Amyloidosis AL Amyloidosis is a rare systemic disorder with a large orphan population (~30-45k combined patients in US/EU) No FDA-approved therapies for the treatment of AL Amyloidosis Pre-clinical data shows high selectivity and binding affinity to multiple AL light-chain subtypes Phase 1a/1b data demonstrated rapid improvement in both functional (12 weeks) and biomarker measures (3 weeks) Advanced preparations are underway to test CAEL-101 in a broad Phase 2 program; potential for accelerated approval in high mortality population CAEL-101 is a rationally designed antibody that has shown rapid improvement in both functional and biomarker endpoints in a Phase 1a/b clinical study 2

4 Key leadership Michael Spector President and Chief Executive Officer, Caelum Dr. Suzanne Lentzsch Chair of Scientific Advisory Board, Caelum Paul Brooke Chairman, Caelum David Barrett CPA Director, Caelum 25 years experience in the pharmaceutical industry Multiple prior roles at GlaxoSmithKline across commercial, GM and R&D Previous roles at Johnson & Johnson, Laurel Pharmaceuticals and North Creek Pharmaceuticals B.S. in biology from University of Pittsburgh and M.B.A. from Rider University Professor of Medicine and Director of the Multiple Myeloma and Amyloidosis Program at the College of Physicians and Surgeons of Columbia University and at New York Presbyterian Hospital Lead clinical investigator of CAEL1-101 P1a/1b trial through November 2017 Fellowship and Residency at Humboldt University (Germany) 40+ years experience in biotech and pharma Previously Head of Global Healthcare Research and Strategy at Morgan Stanley, and Founder and former Managing Partner of VenBio Serves on the board of directors of Incyte and several privately held companies BA from Columbia College and MA from Columbia University Strategic Advisor at Assembly Biosciences, previously served as COO, CFO, and CAO BS in Accounting and Economics and MS in Accounting from Florida University Dr. Lindsay Rosenwald Chairman, President and CEO, Fortress Biotech Chairman, President and CEO of Fortress Biotech Founded Cougar Biotechnology, Chelsea Therapeutics, Cypress Bio, Keryx and Indevus, cofounded Ziopharm and TG Therapeutics, and former director of BioCryst 13 FDA approvals from companies founded B.S. in finance from Pennsylvania State University and M.D. from Temple University School of Medicine 3

5 Three Main Types of Systemic Amyloidosis: CAEL-101 Is Targeted to Primary (AL) Subtype Systemic amyloidosis are a group of protein-misfolding diseases with different individual disease pathologies Rationally designed drugs must be targeted toward the specific precursor protein AL amyloidosis AA amyloidosis Hereditary amyloidosis (ATTR) Prevalence ~30k - 45k (1)(2) ~10k 15k (1)(3) ~50k (4)(5) Precursor protein Immunoglobulin light chains Serum amyloid A protein Transthyretin Point of misfolding Plasma cells (bone marrow) Liver cells Liver cells Cause Acquired mutation and overproduction Overproduction secondary to chronic Hereditary mutation of TTR infections / inflammation (e.g. RA, IBD) Organs commonly affected Heart, kidney, liver Kidney, liver, spleen Nerves, heart, kidney Prothena NEOD001 Discontinued Patisiran Inotersen Developed to specifically bind to the AL light chain Identified from an amino-terminal peptide fragment from human kappa light chain CAEL-101 is a chimeric fibril reactive mab that binds to both kappa and lambda light chains NEOD001 was derived from Serum amyloid A protein and developed to bind to C-terminal region Repurposed and studied as a treatment for AL Amyloidosis Tafamidis AG10 Caelum has shown rapid improvement at fixed time points in both GLS and NTproBNP Prothena failed to demonstrate best response in NT-proBNP in phase 2b/3 trials GLS and NT-proBNP (fixed time point and response) are standard endpoints Source: Blancas-Mejia, Luis M., and Marina Ramirez-Alvarado. Systemic Amyloidoses. Annual Review of Biochemistry, vol. 82, no. 1, 2013, pp Note: GSK is developing an Anti-Sap antibody for the treatment of AA Amyloidosis; the program is early with limited cardiac data. (1) Estimated patient populations in the US and Europe. (3) Bellus Health Press Release, June 20, (2) (4) Estimated worldwide patient population. (5) AlnylamCorporate Presentation, February

6 AL Amyloidosis: many patients have severe organ damage at diagnosis Rare systemic disease characterized by misfolding of pre-amyloid light chain proteins produced by plasma cells U.S. and Europe Population Newly-diagnosed patients in the U.S. per year Misfolded proteins are toxic and aggregate as fibrils Fibrils deposit in and around tissues causing damage and affecting function Symptoms of AL Amyloidosis frequently mimic other diseases (e.g. CHF, respiratory distress, proteinuria), often leading to misdiagnosis ~30k - 45k ~4.5k Potentially understated given AL Amyloidosis often mis-diagnosed Plasma cell production Plasma cell therapies CAEL-101 may neutralize Mechanism of Amyloid formation in tissues CAEL-101 potentially dissolves and removes Bone Plasma cells are produced in the bone marrow Plasma cells produce proteins. Abnormal plasma cells produce misfolded proteins called pre-amyloid light chain proteins which are toxic to cardiomyocytes Misfolded proteins collect together Collections of misfolded proteins create amyloid fibrils Amyloid fibrils deposit in tissues Heart and kidney impacted in 60-75% of patients Image of uptake of CAEL-101 in the myocardium 5

7 And die before getting benefit from current standard of care No FDA-approved therapies for AL Amyloidosis An effective treatment would: a) reduce plasma light chain production; and, b) eliminate existing light chains and amyloid fibrils infiltrating organs Current standard-of-care inhibits plasma cells through either cytotoxic or anti-cd38 therapy Current treatments Anti-CD38s Traditional chemotherapy agents Proteasome inhibitors and immunomodulators Stem cell therapy and organ transplants (primarily for earlier stage patients) Patients exhibit variable hematological responses, ~10-11 month median time to organ response, and high morbidity and mortality Median time to response for CAEL-101 vs. current standard-of-care Standard of care CAEL-101 NT-proBNP 10.4 months 3 weeks GLS No change seen over 12 months Improvement seen after 12 weeks One-year mortality rate of approximately 50% in patients with cardiac disease; 5 months mean overall survival for most severe patients (2) (1) NT-proBNP > 8,500 ng/l. (2) Stage 4 patients based on the Mayo Clinic s staging system. 6

8 CAEL-101 is first-in-class anti-al amyloid mab CAEL-101 Amyloid type In-vitro binding Animal imaging Human amyloid dissolution in mice Human imaging Cardiac response (1) (Biomarker and functional data) Specific for AL misfolded light chain protein Strong in-vitro binding with high specificity to a neo epitope that forms on kappa and lambda misfolded proteins, but is not present on the native light chains Clear co-location of CAEL-101 with human amyloid (both kappa and lambda sub-types) in murine models 7 different human amyloid samples; all were fully cleared rapidly In vivo binding in human imaging studies, including the heart Phase 1a/1b (n=27) Biomarker: 67% response with single dose or 4 weekly doses 3 week median time to response Functional: 90% of cardiac patients responded (statistically significant improvement) Clinical efficacy in kappa and lambda subtypes CAEL-101 is a rationally designed antibody that has shown rapid improvement in both functional and biomarker endpoints in a Phase 1a/b clinical study (1) Biomarker response measured by >30% and >300 pg/ml decrease in baseline NT-proBNP, functional response measured by change in left ventricular function in an echocardiogram analysis. 7

9 Open label dose escalation Phase 1a/b, open-label dose escalation study completed in 2017 Patient criteria Patients with relapsed or refractory AL Amyloidosis Refractory AL Amyloidosis patients had no prior organ response; or Relapsed AL Amyloidosis patients had a prior organ response from chemotherapy Phase 1a n=8 Single IV week 1 Phase 1b n=19 Weekly IV infusion for 4 weeks 1-4 Primary endpoint Establish maximum tolerated dose (up to 500mg/m2) of CAEL-101 Secondary endpoints Cardiac response (NTproBNP) Renal response (24-hour Proteinuria) Pharmacokinetic profile (single dose vs. multiple weekly doses) Select exploratory endpoints GLS Phase 1a and 1b data presented at ASH in 2016 and

10 Encouraging Early Functional Data 9 out of 10 cardiac patients improved against baseline Left ventricular data: All Phase 1b Cardiac Patients (N=10) Mean absolute improvement of 1.69 points in GLS scores (range of -10 to -20 points) in Phase 1b cardiac patients after 12 weeks Importance of GLS Mean Increasingly recognized as a more effective technique than conventional ejection fraction in detecting subtle changes in left ventricular (LV) function (1) Considered to be a sensitive measure of pre-treatment cardiac functional impairment in AL (cardiac) amyloidosis and a predictor of survival over and above cardiac biomarkers (2) Improvement Evidence suggests cardiac AL amyloidosis patients treated with chemotherapy showed no change in GLS from baseline to 1 year (3) Reduced LV longitudinal function was shown to serve as an independent predictor of survival in AL amyloidosis (4) (1) Krishnasamy et. Al. 2015, Left Ventricular Global Longitudinal Strain (GLS) Is a Superior Predictor of All-Cause and Cardiovascular Mortality When Compared to Ejection Fraction in Advanced Chronic Kidney Disease. (2) Salinaro et. Al. 2016, Longitudinal systolic strain, cardiac function improvement, and survival following treatment of light-chain (AL) cardiac amyloidosis. (3) Salinaro et. Al. 2016, Longitudinal systolic strain, cardiac function improvement, and survival following treatment of light-chain (AL) cardiac amyloidosis. No change in GLS was seen from baseline to 1 year both in patients that were recorded as achieving a hematologic complete response and those that did not achieve a complete response. (4) Buss et Al. 2012, Longitudinal Left Ventricular Function for Prediction of Survival in Systemic Light-Chain Amyloidosis: Incremental Value Compared With Clinical and Biochemical Markers. 9

11 LSMean (SE) changes from baseline in NTproBNP Positive Initial Biomarker Data Biomarker data: Evaluable Phase 1b Cardiac Patients (N=8) Treatment period Post treatment period 0 Mean of 8 patients (200) (400) (600) (800) Mean 35.6% improvement in NTproBNP levels in 8 evaluable cardiac patients after 4 weeks (1,000) Data shows positive improvement during the treatment period followed by reversal post treatment period 10

12 Phase 1b cardiac patients: GLS and NT-proBNP data measured at fixed time points with consistent directional trend Functional (global longitudinal strain) Biomarker (NT-proBNP) (1) Absolute change in GLS score from baseline to 12 weeks after baseline Dose (mg / m 2 ) Mean (1.69) Mean Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Patient 9 Patient (3.81) (3.07) (1.99) (2.21) (2.05) (1.94) (1.23) (1.23) (0.43) 1.12 Change from baseline to last dose (week 4) (pg/ml) Patient 10 (1,105) Patient 2 Patient 3 Patient 4 Patient 5(1,148) Patient 6 Patient 7 Patient (1,182) 8 Patient 9 Patient 10 (5.00) (4.00) (3.00) (2.00) (1.00) (1350) (850) (350) 150 Data measures taken at pre-determined time points which is considered more robust than best response data (1) Mean baseline NTpro-BNP was 1,797. (2) Patient 9 and 10 were not evaluable for biomarker response as baseline NT-proBNP was less than 650 pg/ml. Mean (641) (445) (415) (316) (348) (171) NA (2) NA (2) from baseline (35.6%) (29.0%) (49.8%) (28.2%) (30.1%) (45.0%) (18.5%) (42.7%) (41.3%) 11

13 Case Study 1: Organ response occurs independent of depth of response to chemotherapy Patient with cardiac lambda AL Amyloidosis Six prior treatments with no organ response Best prior hematologic response was PR partial response Following the initial dose of CAEL-101, the patient s NT-proBNP level decreased for three consecutive periods A clinically meaningful organ response was observed after only three weeks but the patient continued to have an insufficient hematologic response Case study shows the antibody effect of CAEL-101 on the heart as well as its potential to neutralize the toxic pre-amyloid light chain protein Source: 2017 ASH Presentation from Dr. Suzanne Lentzsch. 12

14 Case Study 2: Co-location of Amyloid, CAEL-101, Neutrophils, and Macrophages Phase 1a patient (lambda light chain) showed symptoms of rash and pruritus after a single dose of CAEL-101 Onset 4 days after infusion, duration of 11 days Skin biopsy showed amyloid caused by lambda light chain Subcutaneous fat with positive immunohistochemical staining for CAEL-101 Supports the hypothesis of antibody binding and amyloid dissolution Neutrophils and macrophages co-located at the site of amyloid and CAEL-101 Patient developed less pronounced rash and pruritis when re-dosed with 100 mg/m 2 in Phase 1b The same patient also had a sustained cardiac response measured as a reduction in NTproBNP (1) Baseline measurements were taken prior to first dosing on Day 1 for Phase 1a and Phase 1b. 13

15 Case Study 3: Organ response and reduction in liver size occurred independent of free light chain (FLC) response Patient with liver kappa AL Amyloidosis Organ response 8 months before FLC response US-Liver Pre-treatment 6/2/16: The liver is enlarged with normal echogenicity. The liver measures 19.4 cm in length. Liver surface is smooth. US-Liver Post-treatment 8/2/16: The liver is normal in size and echogenicity. The surface is smooth. Right lobe measures 17.3 cm in length at the midclavicular. Case study shows enlarged liver returned to normal size in patient that had a hematologic response 8 months post organ response Source: 2017 ASH Presentation from Dr. Suzanne Lentzsch. 14

16 Development of CAEL-101

17 Robust and Unique Development of CAEL Design Specifically designed to bind to light chain fibrils 2. In vitro data (mean % ID / g) Shows high binding specificity to light chains (both kappa and lambda) 11-1F4 specificity 22.0% 9.5% Kd tested against K4 (nm) In vivo data Showed in-vivo binding in animal imaging studies (both kappa and lambda) Kappa Lambda Kd 3. In vivo data (cont d) 4. Clinical data CAEL-101 showed in-vivo binding in human imaging studies Murine models showed CAEL-101 s amyloid clearance ability in 7 different human amyloid samples (2 kappa samples, 5 lambda samples) Mean absolute improvement of 1.69 points in GLS scores (range of 9 20 points) Mean 35.6% improvement in NT-proBNP levels after 4 weeks Mean CAEL-101 is a first-in-class anti-amyloid antibody 16

18 CAEL-101 expedites the clearance of amyloid deposits in a human patient derived xenograft mouse model Results from an in vivo mouse model showed that CAEL-101 dissolved human amyloid deposits taken from seven different patients CAEL-101 cleared both kappa and lambda deposits Day 14 Day 1 Untreated mouse Mice received either CAEL-101 or no treatment Day 14 Amyloid fibril suspensions sourced from human postmortem samples were injected into mice to form amyloid deposits CAEL-101 treated mouse Source: Hrncic et al, Am J Path

19 Amyloid Sub-Type Amyloid Sub-Type CAEL-101 mediates complete clearance of human kappa and lambda amyloid deposits in mouse model Single Dose Multiple Doses Amyloid Deposit Clearance Amyloid Deposit Clearance Day Day k k-01 Not Tested k k-02 Not Tested λ λ-01 Not Tested λ λ λ λ λ λ λ λ Time to Clearance (Days) Untreated Treated Time to Clearance (Days) Untreated Treated Dissolved kappa deposits 10 days faster than the mouse on its own Dissolved lambda deposits ~3 weeks faster than the mouse on its own 18