Calithera Biosciences, Inc. · OTC:CALA
Calithera Biosciences — Investor Presentation (January 2022)
34 slides from Calithera Biosciences's investor presentation, Jan 5, 2022
Slide 1: Targeting cancer, differently.
Targeting cancer, differently. Susan M. Molineaux, Ph.D. | Founder, President & Chief Executive Officer Exhibit 99.1
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation and the accompanying oral commentary contain “forward‐looking” statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “believe,” “will,” “may,” “estimate,” “c
Slide 3: Calithera Today
Calithera Today Core expertise in oncology, discovering and developing novel small molecule enzyme inhibitors Primary focus is on precision oncology Nimble and well-versed in conducting biomarker-driven early and late stage clinical trials Recent addition of two mature mid-stage clinical assets to o
Slide 4: Strong Management Experienced Leadership
Strong Management Experienced Leadership Stephanie Wong Chief Financial Officer & Secretary Eric Sjogren, Ph.D. Senior Vice President of Drug Discovery Susan Demo, Ph.D. Senior Vice President of R&D Operations Matthew Gross Vice President of Business Development Susan Molineaux, Ph.D. Founder, Presi
Slide 5: New Clinical and Preclinical Pipeline
New Clinical and Preclinical Pipeline Synthetic Lethality VPS4A/VPS4B (ATPases) Preclinical program: paralogs Inhibitor to target tumors with one deleted paralog NGS biomarker defined Potential for large market SYK inhibitor Biomarker-defined clinical activity in ABC DLBCL Ph 2A/2B trial in ABC DLBC
Slide 6: Calithera Pipeline: Focus on Precision Oncology
Calithera Pipeline: Focus on Precision Oncology Program Target Indication DISCOVERY PRE-IND PHASE 1 PHASE 2 PHASE 3 MivavotinibSYK ABC DLBCL Sapanisertib mTORC1/2 NRF2 mutated sqNSCLC VPS4A VPS4B mutated solid tumors CB-280 Arginase Cystic Fibrosis Partnered Programs ‘1158 Arginase Solid tumors ATG-
Slide 7: Mivavotinib: SYK inhibitor for NHL
Mivavotinib SYK inhibitor for NHL
Slide 8: Mivavotinib Overview
Mivavotinib Overview SYK Inhibitor Entering a Phase 2 Trial in Diffuse Large B-Cell Lymphoma (DLBCL) 2Schmitz, N Engl J Med 2018;378:1396-407 3Wilson, Cancer Cell 2021;39:1-11 1Gordon, Clin Cancer Res 2020;26:3546-56. C34001 and C34004 CSRs (Unpublished data on file) In NHL trials mivavotinib was ac
Slide 9: Mivavotinib has Durable Single Agent Responses in R/R DLBCL
Mivavotinib has Durable Single Agent Responses in R/R DLBCL 1C34001 and C34004 CSRs (Unpublished data on file) *Mivavotinib 100 mg QD Response evaluable population Probability of Maintaining a Response Months mDOR not reached (95% CI: 7 mos-NE) Pts N* CR ORR R/R DLBCL 81 16% (13/81) 33% (27/81) Miva
Slide 10: Mivavotinib is Differentiated from Other SYK Inhibitors
Mivavotinib is Differentiated from Other SYK Inhibitors SYK Inhibitor ORR Mivavotinib1 33% (27/81)* Entosplentinib2 0% (0/43)** Fostamatinib3 3% (2/68)** Cerdulatinib4 8% (1/12)** Assay Species Mivavotinib Entospletinib Vol of Distribution (L/kg) Rat 9.5 0.55 Dog 6.7 1.45 Tumor/Plasma AUC Ratio Mous
Slide 11: Safety Profile of Mivavotinib in DLBCL is Favorable
Safety Profile of Mivavotinib in DLBCL is Favorable For Development as Monotherapy or in Combination with Other Drugs >300 patients with heme malignancies treated with mivavotinib Favorable safety profile Most common AEs were asymptomatic and reversible laboratory abnormalities Mivavotinib is combin
Slide 12: Current DLBCL Treatment Landscape
Current DLBCL Treatment Landscape R-CHOP Standard treatment for newly diagnosed DLBCL patients Salvage chemotherapy Stem cell transplant CAR-T therapies ADCs (Polatuzumab, Loncastuximab) Antibodies (Tafasitamab) Selinexor Relapse/Refractory Remission High unmet need remains for patients who are inel
Slide 13: DLBCL Disease Characteristics
DLBCL Disease Characteristics ABC (Activated B-Cell) ~50% GCB (Germinal Center B-cell) ~40% Unclassified ~10% DLBCL treatments are the same for all patients, despite the fact that it is a biologically heterogeneous disease3 DLBCL is the most common form of lymphoma, representing ~30% of all NHL diag
Slide 14: SYK Controls Central Activation Pathways in ABC DLBCL
SYK Controls Central Activation Pathways in ABC DLBCL The ABC DLBCL subgroup is defined by chronic activation of the BCR signaling pathway In ABC DLBCL, SYK activates NF-kb and PI3K pathways, driving both proliferation and survival In contrast, in GCB DLBCL SYK activates the PI3K pathway Pathway bio
Slide 15: Mivavotinib Activity is Highest in ABC DLBCL
Mivavotinib Activity is Highest in ABC DLBCL *Response evaluable population Patients of unknown cell-of-origin are excluded Cell of Origin N* ORR ABC (non-GCB) 15 53% GCB 45 22% Retrospective analysis of ORR by cell of origin shows enriched activity in ABC patients R/R DLBCL Unpublished data; combin
Slide 16: MYD88 and CD79b Mutations Hyperactivate SYK
MYD88 and CD79b Mutations Hyperactivate SYK ~50% of ABC DLBCL tumors have one or both mutations1,2 3Munshi, Blood Cancer J 2020;10:12 4Phelan, Nature 2018;560:387-391. 5deGroen, Haematologica 2019;104:2337-48 6Wilson, Nat Med. 2015; 21(8): 922–926 1Schmitz, N Engl J Med 2018;378:1396-407 2Wilson Can
Slide 17: Trial Design for Mivavotinib in R/R ABC DLBCL
Trial Design for Mivavotinib in R/R ABC DLBCL Objectives Further define patient population and refine RP2D dose** Safety and tolerability Anti-tumor efficacy Biomarker validation Enroll biomarker defined cohorts for potential accelerated approval study Primary endpoint: ORR Safety and tolerability S
Slide 18: Clinical Expansion of Mivavotinib Into Other Indications
Clinical Expansion of Mivavotinib Into Other Indications Earlier Stage DLBCL and Other Heme Malignancies Monotherapy (R/R DLBCL) ABC (including MYD88/CD79bm) GCB (biomarker exploration) Combination Mivavotinib + SOC DLBCL drugs Monotherapy (R/R WM) MYD88 mutant (95%) Combination (earlier lines of th
Slide 19: Mivavotinib Summary
Mivavotinib Summary DLBCL projected to be ~$8B market by 2026 High unmet need in R/R for treatments with biomarkers to identify patients most likely to benefit Potential to expand beyond initial line of therapy and indication based on activity as a single agent and combinability as a tolerable, oral
Slide 20: Sapanisertib: mTORC1/2 Inhibitor for NRF2-mutated Squamous NSCLC
Sapanisertib mTORC1/2 Inhibitor for NRF2-mutated Squamous NSCLC
Slide 21: Sapanisertib Overview
Sapanisertib Overview mTORC1/2 Inhibitor Entering a Phase 2 Trial in NRF2-Mutated Squamous NSCLC (sqNSCLC) *NFE2L2 1Paik, J Clin Oncol 2020;38 15 suppl: 9607 A recent Ph 2 trial showed durable single agent activity of sapanisertib in a NRF2m* subset of sqNSCLC patients, a genetically defined group w
Slide 22: Sapanisertib has Durable Single Agent Activity in NRF2m R/R SqNSCLC
Sapanisertib has Durable Single Agent Activity in NRF2m R/R SqNSCLC Patients Paik, J Clin Oncol 2020;38 15 suppl: 9607 Mutation Indication ORR * mPFS NRF2m SqNSCLC 27% (3/11) 8.9 mo KEAP1m SqNSCLC 17% (1/6) KEAP1m + KRASm Adeno NSCLC 0% (0/5) *Sapanisertib at 3 mg QD Response evaluable population NR
Slide 23: NRF2 or KEAP1 mutant tumors activate the oxidative stress pathway
NRF2 or KEAP1 mutant tumors constitutively activate the oxidative stress pathway to support survival NRF2 activation upregulates mTOR activity Sapanisertib inhibits mTORC1/2, blocking proliferation and inducing cell death Sapanisertib is More Active than Other mTOR Inhibitors in NRF2m sqNSCLC Animal
Slide 24: Sapanisertib was Well-tolerated in R/R Solid Tumor Patients
Sapanisertib was Well-tolerated in R/R Solid Tumor Patients Grade ≥3 Adverse Events of any Cause in ≥2% of Patients 1 Paik, J Clin Oncol 2020;38 15 suppl: 9607 (NSCLC) 2 Moore, ESMO Open 2018;3:1-11. (Solid tumors) 3 Phase 1 CSR INK128-001 and Voss et al., Brit J Cancer 2020;123:1590–8. (Solid tumor
Slide 25: Squamous NSCLC Landscape
Squamous NSCLC Landscape https://seer.cancer.gov/statfacts/html/lungb.html Data from TCGA BioPortal https://www.cbioportal.org/ https://www.cancer.gov/types/lung/hp/non-small-cell-lung-treatment-pdq#_359 NCCN NSCLC guidelines June 2021 Garon, Lancet 2014;384:665-73. Rizvi, Oral Abstract OA04.07: Wor
Slide 26: Clinical Development Plan for Sapanisertib
Clinical Development Plan for Sapanisertib Objectives Refine RP2D* and validate NRF2m patient selection strategy Safety and tolerability Anti-tumor efficacy Validate NRF2m biomarker Enroll NRF2m sqNSCLC expansion cohort for single arm or randomized study Primary endpoint: ORR (potential accel approv
Slide 27: Potential to Treat NRF2/KEAP1 Mutations in Other Tumor Types
Potential to Treat NRF2/KEAP1 Mutations in Other Tumor Types Many patients could potentially benefit from treatments specific to this pathway Data from TCGA BioPortal https://www.cbioportal.org/ Histology NRF2 mutation frequency KEAP1 mutation frequency Total mutation frequency NSCLC squamous 15% 12
Slide 28: Sapanisertib Summary
Sapanisertib Summary SqNSCLC is expected to be a $4.5B market by 20261 NRF2 mutations account for 15% of all sqNSCLC patients High unmet need for biomarker-driven treatments in sqNSCLC patients NRF2m SqNSCLC Market Opportunity and Unmet Need Sapanisertib Potential 1DRG Nov 2021 Single agent activity
Slide 29: CB-280: Arginase Inhibitor for Cystic Fibrosis
CB-280 Arginase Inhibitor for Cystic Fibrosis
Slide 30: Rationale for Arginase Inhibitors in Cystic Fibrosis
Rationale for Arginase Inhibitors in Cystic Fibrosis Despite recent advances with CFTR modulators, many patients still have impaired lung function Arginase plays a critical role in CF airway disease1, 2, 3 Decreases nitric oxide (NO) production4, increases production of polyamines and proline Inhibi
Slide 31: Ongoing Randomized Double Blind Ph1b Trial in CF
Ongoing Randomized Double Blind Ph1b Trial in CF Interim Analysis Key Conclusions CB-280 was well-tolerated, showed linear PK and demonstrated robust dose-related PD effects Encouraging trends seen in disease biomarkers including increased FeNO and decreased sweat chloride Early positive trend seen
Slide 32: Synthetic Lethality in Solid Tumors VPS4A Program
Synthetic Lethality in Solid Tumors VPS4A Program
Slide 33: Synthetic Lethality Research Pipeline: VPS4
Synthetic Lethality Research Pipeline: VPS4 VPS4A and VPS4B are paralog ATPases essential for remodeling intracellular organelle membranes1,2 Loss of function of both paralogs is lethal VPS4B homozygous deletion occurs in 1-3% of several solid tumor types3 VPS4B heterozygous deletion is common acros
Slide 34: Calithera Today: Significant Value Creation
Calithera Today: Significant Value Creation Three clinical stage programs Biomarker-defined clinical development for our two oncology drugs Upcoming Milestones Data for mivavotinib and sapanisertib expected in 4Q22-1Q23 Leveraging an experienced management team Research pipeline for synthetic lethal
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