SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 OR 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): October 30, 2019
KALEIDO BIOSCIENCES, INC.
(Exact name of registrant as specified in its charter)
|Delaware|| ||001-38822|| ||47-3048279|
|(State or other jurisdiction|
| ||(IRS Employer|
|65 Hayden Avenue|
|(Address of principal executive offices)||(Zip Code)|
Registrant's telephone number, including area code: (617) 674-9000
(Former name or former address, if changed since last report)
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 communications 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 communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))|
|☐||Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))|
Securities registered pursuant to Section 12(b) of the Act:
|Title of each class||Trading Symbol(s)||Name of each exchange on which registered|
|Common Stock, $0.001 Par Value||KLDO||NASDAQ Global Select Market|
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
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. ¨
Item 2.02. Results of Operations and Financial Condition.
On October 30, 2019, Kaleido Biosciences, Inc. announced its financial results for the third quarter ended September 30, 2019. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
Item 7.01. Regulation FD Disclosure
The Company is also furnishing a corporate presentation, attached as Exhibit 99.2 to this Current Report on Form 8-K, which the Company intends to use from time to time in meetings with investors and others. The corporate presentation will also be available in the investor relations section of the Company’s website at http://kaleido.com.
The information in this Form 8-K (including Exhibits 99.1 and 99.2) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01. Financial Statements and Exhibits.
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.
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| || || ||KALEIDO BIOSCIENCES, INC.|
| || || || |
|Date: October 30, 2019|| || || ||By:|| ||/s/ Alison Lawton|
| || || || || || ||Alison Lawton|
| || || || || || ||Chief Executive Officer, President and Director|
Kaleido Biosciences Reports Third Quarter 2019 Financial Results and Provides Corporate Update
–Executing Pipeline Towards Key Clinical Data Readouts in Q4 2019 and 2020
–Focusing Resources on Pipeline Programs and Extending Cash Runway
LEXINGTON, Mass., October 30, 2019 – Kaleido Biosciences, Inc. (Nasdaq: KLDO), a clinical-stage healthcare company with a chemistry-driven approach to leveraging the microbiome organ to treat disease and improve human health, today announced financial results for the third quarter ended September 30, 2019, and provided a corporate update.
“Over the last two years we have invested in building our platform, including expanding our library of more than 1,500 MMTs and manufacturing capabilities. We have made important progress across the business, and today we have four ongoing clinical studies with three MMTs in three different patient populations, and presented encouraging data from a fifth study at the SSIEM meeting last month. We are also leveraging collaborations to advance our understanding of the potential of our MMTs in promising areas of health and disease where the microbiome is implicated, such as immuno-oncology,”
said Alison Lawton, President and Chief Executive Officer of Kaleido. “We are focusing our resources on our current pipeline, executing against key clinical milestones while optimizing our operational efficiencies to extend our cash runway. We anticipate results from our studies of KB174, including in patients with cirrhosis, during Q4 2019, and next year from our KB109 multi-drug resistant pathogens program and Phase 2 trial of KB195 in patients with urea cycle disorders.”
Corporate Update and Anticipated Milestones
•Dosing is underway in the Phase 2 trial (UNLOCKED) designed to evaluate KB195 in 18-24 patients with urea cycle disorders (UCD). Kaleido, in consultation with study investigators who are leaders in the clinical management of UCD patients, has elected to adjust the primary endpoint for this study in a rare orphan disease population to a within-patient responder analysis of the proportion of patients with ³15 percent decrease in fasting plasma ammonia. The original primary endpoint, 24-hour area under the curve plasma ammonia, will be measured as a secondary endpoint. The Phase 2 trial was initiated approximately 24 months after conducting the first ex vivo screening, and data are expected in mid-2020.
•Results from two clinical studies for Kaleido’s hepatic encephalopathy program evaluating KB174 in patients with well-compensated cirrhosis and in healthy volunteers are expected during Q4 2019.
•Enrollment continues in the clinical study (VITORA) assessing KB109 in patients colonized with multi-drug resistant pathogens, and data are anticipated in mid-2020.
•Kaleido is undertaking measures to focus resources on its pipeline programs, enhance operational efficiencies and extend its cash by approximately a quarter with runway into Q4 2020. This includes decreasing manufacturing and other external costs as well as reducing headcount by approximately 25 percent.
•Entered into a research collaboration with Jeffrey Gordon, M.D., Director of the Edison Family Center for Genome Sciences and Systems Biology at Washington University School of Medicine, to explore the influence of MMTs on microbial and host physiology and metabolism.
•Announced a collaboration with Gustave Roussy, the largest cancer treatment center in Europe, to identify and characterize MMT candidates with the potential to improve cancer immunotherapy efficacy; the research program is aimed at increasing the number of patients who respond to inhibitors of immune checkpoints by changing their microbiome composition and metabolic output.
•Presented data at the annual Society for the Study of Inborn Errors of Metabolism Symposium (SSIEM) from a clinical study of KB195 in patients with UCD which demonstrated safety and tolerability and potential for effect on nitrogen metabolism, a biomarker of ammonia production.
•Presented at IDWeek 2019™ ex vivo data showing that KB109 reduced the relative abundance of multi-drug resistant pathogens in microbiome samples from two different populations at high risk for infection, patients in the intensive care unit who had received broad-spectrum antibiotics and patients with end-stage liver disease.
•Presented ex vivo and in vivo data demonstrating the ability of MMTs to reduce toxic side effects of chemotherapy through multiple mechanisms at the Keystone Symposia on the Microbiome: Therapeutic Implications.
Third Quarter 2019 Financial Results
For the third quarter ended September 30, 2019, Kaleido reported a net loss of $22.0 million, or $0.74 per common share, compared to $17.4 million, or $3.38 per common share for the third quarter ended September 30, 2018.
In the third quarter of 2019, Kaleido invested $16.2 million in research and development (R&D) related to advancing its product pipeline, as compared to $10.2 million in the third quarter of 2018. This year-over-year increase was driven primarily by incremental R&D spending for KB195, including the Company’s Phase 2 clinical trial and external manufacturing. Additional incremental spend year-over-year related to ongoing clinical studies, including two clinical studies for Kaleido’s hepatic encephalopathy program evaluating KB174, and the VITORA clinical study of KB109 in multi-drug resistant pathogens.
General and administrative (G&A) expenses were $5.9 million during the third quarter of 2019, as compared to $7.1 million for the third quarter of 2018. This year-over-year decrease was driven primarily by lower stock-based compensation costs related to G&A.
Included in net loss was non-cash stock-based compensation expenses of $2.9 million for the third quarter of 2019, as compared to $3.8 million in the third quarter of 2018.
As of September 30, 2019, the Company reported cash and cash equivalents of $81.3 million.
About Microbiome Metabolic Therapies (MMT™)
Kaleido’s Microbiome Metabolic Therapies, or MMTs, are designed to drive the function and distribution of the microbiome organ’s existing microbes in order to decrease or increase the production of metabolites, or to advantage or disadvantage certain bacteria in the microbiome community. The Company’s initial MMT candidates are targeted glycans that are orally administered, have limited systemic exposure, and are selectively metabolized by enzymes in the microbiome. Kaleido utilizes its human-centric discovery and development platform to study MMTs in microbiome samples in an ex vivo setting, followed by advancing MMT candidates rapidly into clinical studies in healthy subjects and patients. These human clinical studies are conducted under regulations supporting research with food, evaluating safety, tolerability and potential markers of effect. For MMT candidates that are further developed as therapeutics, the Company conducts clinical trials under an Investigational New Drug (IND) or regulatory equivalent outside the U.S., and in Phase 2 or later development.
About Kaleido Biosciences
Kaleido Biosciences is a clinical-stage healthcare company with a differentiated, chemistry-driven approach to leveraging the microbiome organ to treat disease and improve human health. The Company has built a human-centric proprietary product platform to enable the rapid and cost-efficient discovery and development of novel Microbiome Metabolic Therapies (MMT™). MMTs are designed to modulate the metabolic output and profile of the microbiome by driving the function and distribution of the organ’s existing microbes. Kaleido is advancing a broad pipeline of MMT candidates with the potential to address a variety of diseases and conditions with significant unmet patient needs. To learn more, visit https://kaleido.com/.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the therapeutic potential of our MMT candidates, the timing of initiation, completion and reporting of results of our clinical studies and our strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to the breadth of our pipeline of product candidates, the strength of our proprietary product platform, the efficiency of our discovery and development approach, the clinical development and safety profile of our MMT candidates and their therapeutic potential, whether and when, if at all, our MMT candidates will receive approval form the U.S. Food and Drug Administration and for which, if any, indications, competition from other biotechnology companies, and other risks identified in our SEC filings, including our most recent Quarterly Report on Form 10-Q, and subsequent filings with the SEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements.
|Kaleido Biosciences, Inc. and Subsidiaries|
|Condensed Consolidated Statement of Operations (unaudited)|
|(in thousands, except share and per share data)|
|Three Months Ended September 30,||Nine Months Ended September 30,|
|Research and development||$||16,188 || ||$||10,168 || ||$||50,145 || ||$||26,854 || |
|General and administrative||5,930 || ||7,144 || ||17,544 || ||13,024 || |
|Total operating expenses||22,118 || ||17,312 || ||67,689 || ||39,878 || |
|Loss from Operations||(22,118)|| ||(17,312)|| ||(67,689)|| ||(39,878)|| |
|Other (expense) income||157 || ||(94)|| ||870 || ||(636)|| |
|Net loss||$||(21,961)|| ||$||(17,406)|| ||$||(66,819)|| ||$||(40,514)|| |
|Net loss per share attributable to common shareholders—basic and diluted||$||(0.74)|| ||$||(3.38)|| ||$||(2.76)|| ||$||(8.22)|| |
|Weighted-average common shares outstanding used in net loss per share attributable to common shareholders—basic and diluted||29,856,233 || ||5,146,301 || ||24,224,359 || ||4,931,183 || |
|Kaleido Biosciences, Inc. and Subsidaries|
|Condensed Consolidated Balance Sheet Data (unaudited)|
|September 30,||December 31,|
|Cash and cash equivalents||$||81,272 || ||$||76,086 || |
|Other assets||9,940 || ||9,239 || |
|Total assets||$||91,212 || ||$||85,325 || |
|Liabilities and stockholders' (deficit) equity|
|Liabilities||$||25,172 || ||$||28,343 || |
|Preferred stock||$||— || ||153,226 || |
|Stockholders' (deficit) equity||66,040 || ||(96,244)|| |
|Total liabilities and stockholders' equity||$||91,212 || ||$||85,325 || |
Company Overview October 30, 2019 1 ©2019 KALEIDO™
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the anticipated use of our existing cash resources, the duration for which our existing capital resources will fund our operations, the therapeutic potential of our Microbiome Metabolic Therapy (MMT) candidates, the timing of initiation, completion and reporting of results of our clinical studies and our strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this presentation are based on management’s current expectations and
beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including, without limitation, those related to the planned Phase 2 clinical trial for KB195 for the treatment of UCD, including timeline for initiation, completion and reporting of results, the preclinical and clinical development and safety profile of our MMT candidates and timelines associated with the programs for such MMT candidates, whether and when, if at all, our MMT candidates will receive approval from the U.S. Food and Drug Administration or other applicable regulatory agencies, if any, competition from other biotechnology companies, and other risks identified in our SEC filings, including our final prospectus for our initial public offering, and subsequent filings with the SEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. 2 ©2019 KALEIDO™
The 1st Company to Use a Chemistry-Driven Approach to Systematically DRIVE FUNCTIONAL OUTPUTS OF THE MICROBIOME ORGAN Leveraging Human-Centric Discovery and Development to Rapidly Translate the Promise of the Microbiome Into Solutions for Patients 3 ©2019 KALEIDO™
The Kaleido Opportunity Broad Pipeline Human-Centric Faster, More World-Class Proprietary with Large Discovery & Cost-Efficient Leadership Product Platform Market Development Model Team Opportunity Significant Computational Biology and Data Science Capabilities Enable Kaleido to Learn MORE, and Learn FASTER 4 ©2019 KALEIDO™
Built A World-Class Leadership Team Alison Lawton Former GM, Genzyme Biosurgery, President & Chief Executive Officer COO Aura & OvaScience Kate Knobil, M.D. Former CMO, GlaxoSmithKline Chief Medical Officer, Head of R&D Johan van Hylckama Vlieg, Ph.D. Former VP for Microbiome & Human Chief Scientific Officer Health Innovation, Chr. Hansen Clare Fisher Former Group VP, Global Head of Chief Business Officer Transactions & Business Development, Shire Jerald Korn, J.D. Former Senior Vice President, Chief Legal and General Counsel & Corporate Secretary Administrative Officer, TESARO Mike Bonney Former CEO, Cubist Pharmaceuticals Executive Chair THERAPEUTIC AREA BREADTH CLINICAL DEVELOPMENT COMPANY BUILDING MANUFACTURING & TECHNOLOGY DEPTH & REGULATORY 5 ©2019 KALEIDO™
Significant Progress During 2019 Raised $75 million in February IPO and began 5 clinical studies initiated evaluating 3 Microbiome trading on NASDAQ (KLDO) Metabolic Therapy (MMT™) candidates in 3 different patient populations, including: Bolstered our manufacturing capabilities, including completing tech transfer to large-scale – Phase 2 trial of KB195 in UCD enrolling and dosing patients manufacturing partner and manufacturing 4 metric – Results from UCD study presented at SSIEM in September tons of KB195 Ex vivo and clinical study data highlighting Strengthened leadership team with hyperammonemia and MDR pathogen programs and MMT appointments of CSO, CBO and new Board platform presented at EASL, SIMD, IDWeek and Keystone members; expanded Scientific Advisory Board meetings Further confirmation of regulatory support for Established I/O collaboration with Gustave Roussy, development pathway, including IND cleared and Europe’s largest cancer treatment center, to identify MMT 5 CTAs approved for KB195 candidates with potential to increase the number of patients who respond to checkpoint inhibitors Initiated research collaboration with Dr. Jeffery Gordon, Washington University School of Medicine, founder of the modern microbiome field, to explore the influence of MMTs on microbial and host physiology and metabolism 6 ©2019 KALEIDO™
The Microbiome Organ Has the Potential to Address a Broad Range of Diseases The Microbiome is Implicated in Numerous Conditions • NASH/NAFLD Indigenous Bacteria from Gut Microbiota Regulate Host Serotonin Gut Microbiota Regulate Motor Metabolic • Chronic Kidney Disease Biosynthesis Deficits and Neuroinflammation Health in a Model of Parkinson’s • Metabolic Syndrome Disease Nitrogen • Urea Cycle Disorders Anticancer immunotherapy The severity of NAFLD is associated with gut by CTLA-4 blockade relies on the dysbiosis and shift in the metabolic function of the Metabolism • Hepatic Encephalopathy gut microbiota gut microbiota Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models Microbial • MDR Pathogens Ecology • GvHD Microbiota Modulate Behavioral and Physiological Abnormalities Associated Human nutrition, the gut • Oncology with Neurodevelopment microbiome and the immune Immune Disorders system • IBD Modulation • Primary Sclerosing Cholangitis Gut microbiome modulates response to anti-PD-1 immunotherapy • Autism Spectrum in melanoma patients CNS • Multiple Sclerosis An obesity-associated gut • Parkinson’s Disease microbiome with increased capacity for energy harvest 7 ©2019 KALEIDO™Glycans Are Known to Drive Metabolic Shifts that Have an Impact on Host Physiology
We Have a Unique and More Evolved Approach FOCUS Functions Drive of the Existing Bacteria Microbiome Add Bacteria Subtract Bacteria Microbiome Metabolic Therapies, or MMTs (i.e. targeted glycans) “Bugs as drugs” (e.g. fecal microbiota transplants, Composition “Kill the bugs” bacterial therapy) of the (e.g. Antibiotics) Microbiome KNOWLEDGE OVER TIME Unique Chemistries that Can Drive the Functional Output of the Microbiome 8 ©2019 KALEIDO™
Our Microbiome Metabolic Therapies (MMTs) Enable Human-Centric Discovery and Development CHARACTERISTICS ADVANTAGES Drivers of gut metabolism, long history of Initial MMTs are targeted glycans safe human consumption Ability to advance rapidly into the clinic; Related to a class of compounds that is flexibility to develop as therapeutics, food Generally Recognized As Safe (GRAS) or medical food Potentially minimizes off-target Limited systemic exposure biological effects Highly soluble Can be orally administered Novel and proprietary Robust IP portfolio 9 ©2019 KALEIDO™
Human-Centric Discovery & Development Platform Human Data Drives Learning 1 and MMT 3 Optimization EX VIVO SCREENING RAPID IN HEALTHY ADVANCEMENT INTO MICROBIOME SAMPLES HUMAN CLINICAL 1 Healthy & Patients STUDIES Volunteers MMT DECISION POINT 2 • File IND or global equivalent and Proceed to Phase 2 or later EX VIVO TESTING • Pursue Non-Drug Development IN PATIENT MICROBIOME Pathway/Commercialization SAMPLES Data Collected at Every Stage to Leverage Computational Capability Note(s): 1. Our human clinical studies of our MMT candidates are conducted under regulations supporting research with food, evaluating safety, tolerability and potential markers of effect. For MMT candidates pursuing a drug 10 ©2019 KALEIDO™ development pathway, an IND or regulatory equivalent outside the U.S. will be filed; for those that we elect to continue on a non-drug development pathway, INDs or regulatory equivalent outside the U.S. will not be required.
Faster, More Cost-Efficient Model Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 Kaleido’s Human- Centric Discovery Discovery Human Clinical Studies IND Start and Development1 1 Year 2 Years Phase 2/3 <3 Years Study of Traditional IND Start Pharmaceutical Discovery, Preclinical Phase 1 Phase 2 R&D2 ~5 Years ~1.5 Years or later 5-7 Years Kaleido IND1 Traditional IND Start Phase 2/3 Start Phase 1 ✓ Discovery (human ex vivo) ✓ Dose-response ✓ Discovery Data ✓ Abbreviated preclinical data ✓ Biomarkers may also ✓ Animal Data ✓ Scale for Phase 2/3 be a surrogate for ✓ Scale to Phase 1 efficacy ✓ Human clinical safety, tolerability Note(s): 1. To date with respect to KB195, which we have decided to develop as a drug candidate 11 ©2019 KALEIDO™ 2. DiMasi, Joseph, et. al: Innovation in the pharmaceutical industry: New estimates of R&D costs, Journal of Health Economics, 2016, 47, 20-23.
MMTs Work Through One or More Mechanisms of Action DECREASE ADVANTAGE or DISADVANTAGE Production of Metabolites Certain Species in the Microbiome Community INCREASE Production of Metabolites 12 ©2019 KALEIDO™
Broad Pipeline in Multiple Disease Areas Human Clinical Studies1 Mechanism of Ex Vivo Ex Vivo Healthy PROGRAM Target Action Screening Testing Volunteers Patients IND 2 Phase 13 Phase 2 Phase 3 Hyperammonemia: Urea Ammonia Cycle Disorders (KB195) Hyperammonemia: Hepatic Encephalopathy Ammonia (KB174 or KB195) Infections Caused MDR by Multi-Drug Resistant Pathogens Bacteria (KB109) Cardiometabolic and Liver TMA/Others Diseases Tumor Immuno-oncology Response Mechanism of Action Decrease Production of Metabolites Completed Advantage/Disadvantage Certain Species In Progress Note(s): 1. Our human clinical studies of our MMT candidates are conducted under regulations supporting research with food, evaluating safety, Increase Production of Metabolites Not Required tolerability and potential markers of effect in human subjects. 2. For MMT candidates pursuing a drug development pathway, an IND or regulatory equivalent outside the U.S. will be filed; for those that we elect to continue on a non-drug development pathway, INDs or regulatory equivalent outside the U.S. will not be required. 3. Based on feedback from the FDA and clearance of our IND for KB195 in UCD, we believe we may be able to advance other MMT candidates directly into Phase 2/3. 13 ©2019 KALEIDO™
The Hyperammonemia Opportunity LIVER Main Site of Ammonia Clearance GUT BRAIN Ammonia Main Site of Production Ammonia Toxicity KB195 KB174 / KB195 Urea Cycle Disorders (UCD) Hepatic Encephalopathy (HE) • Neuropsychiatric abnormalities in patients with liver dysfunction • ~500,000 patients in U.S., ~800K in E.U.; many have not been • Inability to convert ammonia due to inborn urea cycle defects diagnosed • Orphan disease with ~3,000 patients in U.S.; ~4,500 in E.U. • Two current approved treatments for Overt HE (OHE) • High unmet medical need despite available treatments • High Unmet Medical Need – Reduce the Risk of Life-Threatening Crises – No current approved treatment for Minimal HE (MHE) – Reduce OHE episodes and infection risk – More tolerable therapy POTENTIAL CLINICAL ENDPOINTS: POTENTIAL CLINICAL ENDPOINTS: • Fasting plasma ammonia and plasma ammonia 24-hour AUC • Time to first breakthrough OHE episode Sources: Batshaw, M. L., et. al. (2014). A longitudinal study of urea cycle disorders, Molecular Genetics and Metabolism, 113(0), 127-130; Montgomery, J. Y., & Bajaj, J. S. (2011). 14 ©2019 KALEIDO™ Advances in the Evaluation and Management of Minimal Hepatic Encephalopathy, Current Gastroenterology Reports, 13, 26-33; Company reports
Ex Vivo Screening & Testing: KB195 Reduced Ammonia in Healthy & Patient Microbiomes Ability to Screen Many MMTs KB195 in UCD Patients 1 Across Our Compound Library for 2 Reduced Ammonia in All Microbiome Samples Ability to Reduce Ammonia Reduced Ammonia by > 50% in 10 Out of 12 Samples Control KB195 Reduced Ammonia by 97%, Compared to Control (water) Ammonia Levels Normalized Normalized AmmoniaControl Levels to KB195 Ammonia Reduction Relative to Control Control (%) to Relative AmmoniaReduction Compound 15 ©2019 KALEIDO™
KB195 Clinical Studies Reduced Nitrogen Metabolism, a Biomarker of Ammonia Production Stable isotope tracer only metabolized by bacterial enzymes in the gut, which separate the urea and lactose portions. Bacterial urease then hydrolyzes urea to ammonia. In Two Clinical Studies: • KB195 was associated with a significant reduction in urinary excretion of 15N tracer in healthy subjects • 15N tracer data suggestive of KB195 activity in reducing nitrogen metabolism in patients with well-controlled UCD 16 ©2019 KALEIDO™
KB195 Clinical Studies Generally Well Tolerated in Healthy Subjects & Patients with Well-Controlled UCD Fewer Healthy Subjects Receiving KB195 Overall Tolerability of KB195 Was Good in Reported Diarrhea (BSS) 10 Patients with Well-Controlled UCD Negative control KB195 Comparator glycan 6 4 4 4 3 3 1 1 1 1 1 18g/day 36g/day 54g/day 72g/day Dosing Period Randomized, controlled, double-blind study in healthy Open-label, single-arm, clinical study in 4 patients with subjects on a high protein diet well-controlled UCD; KB195 added to standard of care • No clinically significant safety signals observed and no serious treatment-emergent adverse events • Generally well tolerated based on measures that included Gastrointestinal Tolerability Questionnaire (GITQ), Bristol Stool Scale (BSS) and overall tolerability scale 17 ©2019 KALEIDO™
KB195 in UCD Clinical Program • Safety/tolerability of KB195 in 4 pts with well-controlled UCD Clinical study (completed) • Impact on ammonia measured by nitrogen metabolism in blood and urine UCD Phase 2 open label clinical trial Data expected mid-2020 • 18-24 patients inadequately controlled on standard of care • 8-week treatment period; dose escalated from 9g (BID) to 36g (BID) • Evaluating ammonia levels, including proportion of patients with 15 percent decrease in fasting plasma ammonia • Safety and tolerability 1H 2019 2H 1H 2020 2H 2021 18 ©2019 KALEIDO™
HE Program Advanced into Clinical Studies 2 KB195 in Microbiome Samples from Initiated two clinical studies of KB174 Hepatically Impaired Patients 3 with data expected in Q4’19 Reduced Ammonia in 18 of 19 Microbiome Samples Outperformed Lactulose in Reducing Ammonia KB174 chosen as lead based on ability to reduce Levels in 14 of 19 Samples ammonia and potential impact on infection rates Clinical study in patients with cirrhosis • Evaluate KB174 compared to a negative control, in adult patients with well-compensated cirrhosis, including: – Nitrogen metabolism – Safety and tolerability Clinical study in healthy volunteers to explore dosing • Assess various dosing levels of KB174 in healthy subjects evaluating: Ammonia Reduction Relative to Control Control (%) to Relative AmmoniaReduction – Nitrogen metabolism – Safety and tolerability 19 ©2019 KALEIDO™
Lead Programs in Hyperammonemia Demonstrate the Power of Our Proprietary Product Platform REGULATORY AGENCY FEEDBACK ON UCD Hyperammonemia • IND cleared in U.S.; KB195 is novel and unique • CTAs approved in UK, Belgium, Germany, Switzerland & Mexico Pathologies that Result in an Excess of Ammonia in the Blood CLINICAL • First clinical study in UCD patients Decrease − No clinically significant safety signals & generally well tolerated Production of − KB195 associated with a general ↓ in urinary 15N excretion, suggestive of KB195 Ammonia activity in reducing nitrogen metabolism • Healthy Volunteer Clinical Study − Lowered net ammonia production1 − Observed ammonia reductions across heterogeneous microbiomes • Clinical data support ex vivo testing results of reduced ammonia in patient microbiome samples Significant SPEED & COST EFFICIENCY VALIDATED Unmet Medical Need • Two MMTs advancing in two diseases resulting in hyperammonemia Urea Cycle Disorders (UCD) • Phase 2 clinical trial initiation ~24 months after first ex vivo screening Hepatic Encephalopathy (HE) VALIDATED MODEL APPLICABLE ACROSS PIPELINE 15 20 ©2019 KALEIDO™ Note(s): 1. As evidenced by lowered urinary N excretion in the non-IND clinical study of KB195 in healthy subjects
The Microbiome and the Immune System are Closely Linked; Many Immune-mediated Diseases Share Common Biology Healthy microbiome Genes, environment, therapeutic/ antibiotic treatment GOAL: GOAL: Increase immune response Reduce immune response (e.g., immuno-oncology) (e.g., MDR pathogens program) Decreased Loss of beneficial Pathobiont diversity microbes expansion Decreased/exhausted Overactive/inappropriate immune response immune response MMT intervention MMT intervention Immune cell ‘boost’ Immune cell modulation Increased immune cell activation & improved disease outcomes Decreased inflammation & 21 ©2019 KALEIDO™ improved disease outcomes
KB109 in Multi-Drug Resistant Pathogens, a Growing Public Health Threat 1 Ex Vivo Screening 2 Ex Vivo Testing 3 Our MMTs Observed to KB109 Observed to Reduce Reduce Pathogens Pathogens by a Median • Initiated clinical study of KB109 in of 45% Relative to Control patients colonized with multi-drug in 10 of 13 Samples resistant pathogens (data expected in mid-2020) • Up to 64 patients evaluating decolonization, safety and tolerability • Data will support MDR pathogens % Pathogen % Control Control (%) program and also inform inflammation / autoimmune discovery Pathogen Reduction Relative to Relative Reduction Pathogen efforts Hours Microbiome Samples from 13 ICU Patients 22 ©2019 KALEIDO™
Collaborating with Gustave Roussy, Pioneer in Immunotherapy and Research in Microbiome and Cancer • Gustave Roussy is a leading center for Gustave Roussy Utilizes Advanced Preclinical Model with Human Microbiomes of Responder (R) and Non-Responder (NR) Patients immunotherapy in Europe – Pioneer in understanding relationship between the microbiome and cancer • Collaboration aimed at improving cancer immunotherapy efficacy by increasing the number of patients who respond to checkpoint inhibitors – Kaleido will analyze intestinal microbiome samples from Microbiome dictates a-PD-1 outcome checkpoint inhibitor non-responder patients and identify MMTs that drive changes in microbial communities associated with favorable response to treatment – Gustave Roussy researchers will use their advanced preclinical models to identify MMTs that stimulate the targeted therapeutic responses • Insights from collaboration expected in Q4 2020 Adapted from: Routy, et. al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors, Science, January 2018; Gopalakrishnan et. al. Gut microbiome modulates 23 ©2019 KALEIDO™ response to anti–PD-1 immunotherapy in melanoma patients, Science, January 2018.
MMT Program for Reduction of TMA in Cardiometabolic and Liver Diseases Our top MMTs reduced TMA by >90% • Two lead MMTs identified in ex vivo testing 1 in Ex Vivo Screening 2 • Mechanistic work ongoing to evaluate Compared To Control several MMTs through validated preclinical models Control • Will be prepared to initiate clinical study 3 supporting TMA program pending results from mechanistic work by YE 2020 24 ©2019 KALEIDO™
Manufacturing is a Core Strategic Advantage Proprietary Methods Standard Small Molecule Unit Operations Scalable and Transferable Internal Manufacturing 3rd Party Manufacturers Production for ex vivo, toxicology, Large scale production for clinical trials and future and human clinical studies commercial supply (Thermo Fisher Scientific) Efficient and scalable process Internal capability to manufacture 12 MMTs per year; potential to double by early 2020 Completed tech transfer to Thermo Fisher in ~6 months, scaled to 1,000 kg with capability to increase by >40X 4 metric tons of KB195 manufactured for Phase 2 trial and toxicology 25 ©2019 KALEIDO™
Robust Global IP Portfolio 9 U.S. Patents + 2 EPO Patents: • Glycan pharmaceutical compositions (Europe) • Methods to reduce ammonia (U.S.) • Methods to treat pathogen colonization (U.S.) • Methods to treat diarrhea (U.S.) • Methods to treat dysbiosis (U.S.) • Catalyst compositions (U.S. and Europe) 100+ Non-Provisional Applications Pending, Worldwide in 20+ Regions/Countries • Glycan compositions • Methods to treat immune imbalances (e.g. cancer) • Methods to modulate short chain fatty acids • Methods of making glycans Continued IP Expansion by Filing Patent Applications Directed to Pharmaceutical Compositions, Methods of Treatment and Methods of Manufacture 26 ©2019 KALEIDO™
Important Upcoming Catalysts Q4 2019 2020 • Data from clinical studies of • Data from Phase 2 clinical trial of KB195 in patients with UCD KB174 in patients with well- (mid-year) compensated cirrhosis and in healthy subjects • Data from clinical study of KB109 in patients colonized with multi- drug resistant pathogens (mid-year) • Finalize development plan and trial design for HE program; be prepared to initiate clinical study in patients (H2) • Ready to initiate first clinical study supporting TMA program, pending results from ongoing mechanistic work (Q4) • Insights from immuno-oncology collaboration with Gustave Roussy (Q4) 27 ©2019 KALEIDO™
The Kaleido Opportunity PLATFORM HUMAN-CENTRIC MODEL PIPELINE TEAM Multiple indications Extensive Enables rapid and MOAs targeting experience, including Expanding number advancement of unmet patient needs company building, Demonstrated of proprietary MMTs, broad portfolio of in significant product development speed and cost IP, computational MMTs by learning markets; human and manufacturing efficiency to the clinic capabilities more and faster from clinical studies across many human data completed and technologies and ongoing therapeutic areas 28 ©2019 KALEIDO™
29 ©2019 KALEIDO™