Xilio Therapeutics, Inc. · NASDAQ:XLO
Xilio Therapeutics — Q1 2022 Earnings Presentation
34 slides from Xilio Therapeutics's earnings presentation, May 12, 2022
Slide 1: Harnessing the Immune System to Improve the Lives of People with Cancer
XILIO THERAPEUTICS (NASDAQ: XLO) HARNESSING THE IMMUNE SYSTEM TO IMPROVE THE LIVES OF PEOPLE WITH CANCER MAY 12, 2022 © 2022 Xilio Therapeutics, Inc.
Slide 2: Forward-looking statements
2 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 plans, strategies, timelines and expectations for Xilio’s current or future approved product ca ndida
Slide 3: Expert leadership team across oncology drug discovery, development and commercialization
3 Expert leadership team across oncology drug discovery, development and commercialization • 20+ years leading biotech companies, R&D and commercialization organizations • Co - founder and chairman of Adagio Therapeutics; previously President and CEO of Arsanis; VP global medical affairs at Cubist P
Slide 4: Building a robust pipeline of tumor-selective immunotherapy programs
4 Building a robust pipeline of tumor - selective immunotherapy programs Tumor - Selective Programs Mechanism of Action Discovery IND - Enabling Phase 1 Phase 2 Phase 3 Anticipated Upcoming Milestones XTX101 (1) Anti - CTLA - 4 Preliminary Phase 1 monotherapy data mid - 2022 XTX202 (2) IL - 2 Prelim
Slide 5: Today's I-O agents offer curative potential but are limited by systemic toxicity
5 Today’s I - O agents offer curative potential but are limited due to systemic toxicity • Improved survival achieved with high dose ipilimumab (anti - CTLA - 4) at 10 mg/kg • 10 - year durable CRs achieved in melanoma with high dose IL - 2 as a monotherapy • Tumor shrinkage observed in patients wit
Slide 6: Today's I-O agents limited by systemic toxicity; GPS designed to solve this
6 Today’s I - O agents offer curative potential but are limited due to systemic toxicity • Multi - organ AEs and peripheral side effects of potent I - O therapy can be lethal • Often results in dose reductions, interruptions or discontinuations for many patients • Many I - O agents remain completely
Slide 7: GPS-enabled therapies designed to unlock the full potential of immuno-oncology
7 GPS - enabled therapies are designed to unlock the full potential of immuno - oncology Geographically precise solutions (GPS) are designed to solve this problem by localizing the desired I - O effect in the tumor Xilio’s GPS Platform: ✓ Engineer highly potent I - O molecules ✓ Designed to be syste
Slide 8: GPS platform components designed to improve I-O therapeutic index
8 GPS platform components designed to work synergistically to improve I - O therapeutic index GPS - enabled Cytokine Half - life extension domain Linker sequences Masking domain Cytokine 5 2 Protease cleavage site 4 1 3 MMP - dependent cleavage at the tumor
Slide 9: Clinical validation of MMP-activated imaging agent in tumor microenvironment
9 Clinical validation of MMP - activated imaging agent in tumor microenvironment in patients Third - party MMP activated imaging agent AVB - 620 validates tumor - dependent MMP expression; selectively highlights tumor tissue in human clinical studies; Breakthrough Designation granted as diagnostic f
Slide 10: GPS platform components designed to improve I-O therapeutic index
10 GPS platform components designed to work synergistically to improve I - O therapeutic index GPS - enabled Cytokine Tumor Microenvironment - Activated Cytokine Half - life extension domain Linker sequences Masking domain Cytokine 5 2 Protease cleavage site 4 1 3 Active cytokine 5 2 Molecule enters
Slide 11: Xilio product candidates are cleaved in the majority of tumor samples
11 Xilio product candidates are cleaved in the majority of tumor samples from patients XTX101 (1) XTX202 (2) XTX301 (3) Cancer Type Sample Size % of Samples Cleaving XTX301 Colon 6 83% H&N 4 75% Lung 8 50% Ovarian 4 50% Prostate 12 67% RCC 6 83% Cancer Type Sample Size % of Samples Cleaving XTX202 C
Slide 12: XTX101 Tumor-Selective Anti-CTLA-4 Product Candidate
12 XTX101 TUMOR - SELECTIVE ANTI - CTLA - 4 PRODUCT CANDIDATE
Slide 13: High-dose ipilimumab improved survival, but utility limited by toxicity
13 Dose Median OS Adverse Events: Grade 3/4 irAEs / discontinuations (%) 3 mg/kg 11.5 mo 14 / 19 10 mg/kg 15.7 mo 30 / 31 High - dose ipilimumab (aCTLA - 4) improved survival, but utility is limited due to known toxicity Standard Approved Dose Ipilimumab Melanoma Randomized Phase 3 Trial irAE: Immun
Slide 14: XTX101 achieved wider therapeutic index than ipilimumab analog in preclinical studies
14 XTX101 (aCTLA - 4) achieved 10 - fold wider therapeutic index than ipilimumab analog in preclinical studies Ipilimumab • Improved activity, higher CTLA - 4 binding affinity and enhanced Fc - driven effector function • Lower peripheral toxicity potential due to masking and tumor - selective activa
Slide 15: XTX101 improved therapeutic index and greater potency than ipilimumab analog in vivo
15 XTX101 (aCTLA - 4) demonstrated improved therapeutic index and 10 - fold greater potency than ipilimumab analog in vivo • 1 MB49 cells were inoculated subcutaneously into C57BL/6 - huCTLA - 4 mice. When tumors reached approximately 150 mm 3 , mice received a single IV dose at the doses indicated
Slide 16: Clinical plan for XTX101 enables efficient path to POC
16 Clinical plan for XTX101 (aCTLA - 4) enables efficient path to POC with substantial opportunities for expansion Initiated patient dosing in September 2021; Preliminary monotherapy data anticipated in mid - 2022 Monotherapy PD Cohort (n=30) PD - 1 Combination with Pembrolizumab Dose Escalation (n=
Slide 17: XTX202 Tumor-Selective IL-2 Product Candidate
17 XTX202 TUMOR - SELECTIVE IL - 2 PRODUCT CANDIDATE
Slide 18: High-dose IL-2 offered curative potential but usage limited by VLS
18 High - dose IL - 2 offered curative potential, but usage limited in patients due to life - threatening VLS Limited use of high - dose IL - 2 in patients with cancer High - dose IL - 2 resulted in PFS >10 years, mostly in patients who achieved a CR * Most develop hypotension, despite strict requir
Slide 19: XTX202 Tumor-selective IL-2 product candidate
19 XTX202 Tumor - selective IL - 2 product candidate • Little or no systemic toxicity observed in preclinical studies; well - tolerated in non - human primates (HNSTD 10 mg/kg) • Preclinical monotherapy activity • Improved therapeutic index in vivo • Curative: durable, monotherapy CRs in RCC and mel
Slide 20: Aldesleukin remains the efficacy bar for XTX202
20 • Low dose: 0.006 mg/kg • Systemically active • Dose limited by systemic toxicity • No objective responses observed with monotherapy in Phase 1 trial (including 24 patients treated at RP2D or higher) Aldesleukin Remains the Efficacy Bar for XTX202 AE = adverse event; CR = complete response; MTD =
Slide 21: XTX202 designed to improve therapeutic index through tumor-selective activation
21 XTX202 (IL - 2) designed to improve therapeutic index through tumor - selective activation XTX202 provided tight, protease - dependent control of IL - 2 activity in vitro H a l f - l i f e e x t e n s i o n d o m a i n L i n k e r s e q u e n c e s M a s k i n g d o m a i n C y t o k i n e 5 2 P
Slide 22: XTX202 improved therapeutic index in vivo
22 XTX202 (IL - 2) improved therapeutic index in vivo : Tumor growth inhibition with substantially less toxicity compared to aldesleukin at its MTD O’Neill et al .., ASCO 2021 • Aldesleukin at MTD of 3 mg/kg BID for 4 days (24 mg/kg total) induced body weight loss and mortality • Non - masked contro
Slide 23: XTX202 well-tolerated in NHPs and overcame toxicity of non-masked control
23 XTX202 (IL - 2) was well - tolerated in NHPs and overcame toxicity observed with non - masked control • XTX202 did not cause peripheral lymphocyte expansion or capillary leakage at repeat doses (weekly x4) up to 10 mg/kg in completed GLP toxicology studies • XTX202 half - life in NHPs of 5.3 days
Slide 24: Clinical plan for XTX202 enables efficient path to POC
24 Phase 1/2 Trial Design Clinical plan for XTX202 (IL - 2) enables efficient path to POC with substantial opportunities for expansion Monotherapy Dose - Escalation (n=40) Monotherapy RCC Efficacy Expansion (n=30) Monotherapy Melanoma Efficacy Expansion (n=30) PD - 1 Combination Dose - Escalation (n
Slide 25: XTX301 Tumor-Selective IL-12 Product Candidate
25 XTX301 TUMOR - SELECTIVE IL - 12 PRODUCT CANDIDATE
Slide 26: IL-12 has anti-tumor potential but is limited by severe systemic toxicity
26 IL - 12 has potential for meaningful anti - tumor activity in a range of tumors but is limited by severe systemic toxicity • IL - 12 induces objective responses in patients • Systemic IL - 12 therapy causes severe life - threatening hepatotoxicity • Currently no FDA - approved IL - 12 therapies X
Slide 27: XTX301 demonstrated improved therapeutic index in vivo
27 XTX301 (IL - 12) demonstrated improved therapeutic index in vivo • Safety in NHPs: XTX301 was well - tolerated in multiple dose studies at doses up to 1.5 mg/kg, while non - masked control was not tolerated (fatal toxicity) at doses down to 0.03 mg/kg Tumor Growth Inhibition 1 Body Weight 2 mXTX3
Slide 28: mXTX301 elicited pharmacodynamic effects in tumors with effective peripheral masking
28 mXTX301, a mouse surrogate for XTX301 (IL - 12), elicited pharmacodynamic effects in tumors and exhibited effective peripheral masking in mouse models • Treatment with mXTX301 resulted in intra - tumoral induction of IFNg in B16F10 and MC38 tumor bearing mice with low peripheral exposure 1. A one
Slide 29: Building a Leading Immuno-Oncology Company
29 BUILDING A LEADING IMMUNO - ONCOLOGY COMPANY
Slide 30: Building a robust pipeline of tumor-selective immunotherapy programs
30 Building a robust pipeline of tumor - selective immunotherapy programs Tumor - Selective Programs Mechanism of Action Discovery IND - Enabling Phase 1 Phase 2 Phase 3 Anticipated Upcoming Milestones XTX101 (1) Anti - CTLA - 4 Preliminary Phase 1 monotherapy data mid - 2022 XTX202 (2) IL - 2 Preli
Slide 31: GPS platform potential beyond cancer
31 GPS platform has potential to deliver highly potent, geographically localized immunotherapies beyond cancer Potential to harness unique protease profiles of different diseases to deliver therapeutics that enhance or inhibit immune activity at the disease site without systemic toxicity Masked Anti
Slide 32: Building a team committed to oncology innovation
32 Building a team that is passionately committed to oncology innovation to transform patients’ lives
Slide 33: First quarter 2022 financial results
33 First quarter 2022 financial results * Unaudited Balance Sheet March 31, 2022 December 31 , 2021 Cash and Cash Equivalents $177.0M $198.1M Statement of Operations Three Months Ended March 31, 2022* 2021* Research & Development Expenses $14.9M $11.6M General & Administrative Expenses $6.3M $4.9M N
Slide 34: Focused on harnessing the immune system to achieve deep and durable clinical responses
34 z Focused on harnessing the immune system to achieve deep and durable clinical responses in cancer ✓ GPS platform enables engineered molecules that localize activity within the tumor microenvironment ✓ XTX101 (anti - CTLA - 4) preliminary Phase 1 monotherapy cohort data anticipated in mid - 2022