Calithera Biosciences, Inc. · OTC:CALA
Calithera Biosciences — Investor Presentation (October 2021)
35 slides from Calithera Biosciences's investor presentation, Oct 19, 2021
Slide 1: Targeting cancer, differently
Targeting cancer, differently. Susan M. Molineaux, Ph.D. | Founder, President & Chief Executive Officer Exhibit 99.2
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: Clinical-stage precision oncology biopharmaceutical company
is a clinical-stage, precision oncology biopharmaceutical company developing targeted therapies to redefine treatment for biomarker-specific patient populations
Slide 4: Transformative Acquisition
Transformative Acquisition Sapanisertib (TAK-228; mTORC1/2 inhibitor) Calithera has acquired two Phase 2 oncology compounds from Takeda Both compounds have single agent clinical activity and the potential to be first-to-market drugs in biomarker-defined populations of cancer patients Mivavotinib (TA
Slide 5: Robust pipeline of targeted, biomarker-defined small molecules
Robust pipeline of targeted, biomarker-defined small molecules DISCOVERY PRE-IND PHASE 1 PHASE 2 PHASE 3 Telaglenastat (CB-839) Glutaminase Inhibitor: KEAP1/NRF2* mutated nsqNSCLC Sapanisertib (CB-228) mTORC1/2 Inhibitor: NRF2* mutated squamous NSCLC Lung KEAP1/NRF2* mutation KEAPSAKE Mivavotinib (C
Slide 6: Telaglenastat and Sapanisertib KEAP1/NRF2 Programs
Telaglenastat and Sapanisertib KEAP1/NRF2 Programs
Slide 7: Telaglenastat in Non-Squamous NSCLC with KEAP1 or NRF2 mutations
Telaglenastat Glutaminase Inhibitor in Development for Non-Squamous NSCLC Patients Harboring KEAP1 or NRF2 mutations
Slide 8: KEAP1/NRF2 Mutations Protect Cancer Cells from Oxidative Stress
KEAP1/NRF2 Mutations Protect Cancer Cells from Oxidative Stress KEAP1/NRF2 mutated cells are highly dependent on glutamine metabolism and glutathione production Increases expression of >200 genes involved in oxidative stress pathways, including glutamine metabolism and glutathione production Hayes a
Slide 9: Telaglenastat In KEAP1/NRF2-Mutated nonsquamous NSCLC
Telaglenastat In KEAP1/NRF2*- Mutated nonsquamous NSCLC SOC=pembrolizumab, carboplatin, pemetrexed (PCP) *also referred to as NFE2L2 https://www.cbioportal.org/ Gadjeel et al. LB-397, AACR 2020 Skoulidis et al. J Clin Oncol 38: 2020 (suppl; abstr TPS9627) ASCO 2020 https://clinicaltrials.gov/ct2/sho
Slide 10: KEAP1mut Tumors are Sensitive to Telaglenastat
KEAP1mut Tumors are Sensitive to Telaglenastat KRASmut p53mut KRASmut p53mut KEAP1mut KEAP1mut mouse tumors are more aggressive than KEAP1wt Telaglenastat (CB-839) has anti-tumor activity in KEAP1mut but not KEAP1wt tumor models Krasmut/Keap1mut are often co-incident in lung cancer Nat Med. 2017 Nov
Slide 11: KEAPSAKE: Telaglenastat and Standard of Care in 1L NSCLC
KEAPSAKE: Telaglenastat and Standard of Care in 1L Patients With KEAP1/NRF2-mutated Non-squamous NSCLC Ongoing Randomized Ph2 Trial Placebo Pembro + Chemo 1L nsqNSCLC Stage IV N = 120 KEAP1/NRF2-mutation detected by NGS/liquid biopsy Double-blinded and placebo controlled Telaglenastat Pembro + Chemo
Slide 12: KEAP1 or NRF2 Mutations: Large, Underserved NSCLC Population
Patients with KEAP1 or NRF2 Mutations Comprise a Large, Underserved Patient Population in NSCLC 1. Evaluate Pharma, 2021,WW forecast 2026 2. NIH/ NCI SEER Program, Cancer.net 3. cBioPortal, August 2020, KEAP1, NFE2L2 (NRF2) gene mutations. Best, Cell Cycle, 2018, Vol. 17, No 14. NSCLC market is expe
Slide 13: Sapanisertib in Squamous NSCLC with NRF2 mutations
Sapanisertib mTORC1/2 Inhibitor in Development for Treatment of Squamous NSCLC patients whose tumors harbor NRF2 mutations
Slide 14: Sapanisertib Targets a Key Survival Mechanism in Mutated Tumor Cells
Uncontrolled oxidative stress in rapidly dividing tumor cells leads to cell death mTORC1/2 drives NADPH production, critical for relieving oxidative stress and promoting tumor cell survival KEAP1/NRF2 mutations activate NRF2, increasing expression of anti-oxidant genes By blocking NADPH production,
Slide 15: Sapanisertib Differential Anti-tumor Activity In Vivo
Sapanisertib Exhibited Differential Anti-tumor Activity over mTOR1 and other mTORC1/2 inhibitors In Vivo LK-2 xenograft harboring NRF2m treated with sapanisertib (MLN0128), everolimus, AZD2014 (vistusertib), and deforolimus at the indicated doses. Sapanisertib alone demonstrated anti-tumor efficacy
Slide 16: Sapanisertib Overview
Sapanisertib Overview Sapanisertib is an mTORC1/2 inhibitor with single-agent clinical activity in NRF2*m sqNSCLC1 NRF2 mutations occur in ~15% of sqNSCLC patients2 Sapanisertib exhibits differential anti-tumor activity compared to rapalog inhibitors of TORC1 in NRF2-mutant squamous NSCLC in vivo mo
Slide 17: Squamous Non-Small Cell Lung Cancer Treatment Overview
Squamous Non-Small Cell Lung Cancer Treatment Overview >235,000 diagnosed with NSCLC in the US each year, ~25-30% of those are squamous NSCLC1-2 Actionable mutations are only found in 1-5% of squamous NSCLC patients, leaving patients few options after PD1 inhibitors and chemo3,4 The standard-of-care
Slide 18: Sapanisertib Durable Single Agent Activity in R/R NRF2m Squamous NSCLC
R/R NRF2m SqNSCLC pts (n=11)1 27% (3/11) ORR 55% (6/11) with durable clinical benefit (PR or SD >6m) R/R KEAP1m SqNSCLC pts (n=6) 1 16% (1/6) ORR No responses in adeno NSCLC KEAP1m/KRASm Dose: 3 mg QD Median lines of prior therapies: 2 Standard-of-care mPFS in R/R sqNSCLC is 3-4.5 mos2, 3 Sapanisert
Slide 19: Sapanisertib is Well-tolerated in R/R NSCLC Patients
Sapanisertib is Well-tolerated in R/R NSCLC Patients Predominantly Grade 1 / 2 adverse events at 3mg QD Adverse Event Grade 1 Grade 2 Grade 3 Grade 4/5 Hyperglycemia 70% 70% 47%* 0 Fatigue 20% 30% 0 0 Weight Loss 20% 7% 0 0 Anorexia 17% 17% 3% 0 Nausea 17% 3% 3% 0 Pruritis 17% 7% 0 0 Mucositis 13% 3
Slide 20: Planned Sapanisertib Trials
Planned Sapanisertib Trials Additional Development Plans: Generate data in KEAP1m squamous NSCLC Explore potential in KEAP1/NRF2m tumor types beyond NSCLC Biomarker-Driven Clinical Development Plan for Sapanisertib NRF2m squamous NSCLC Primary endpoint: OS R/R NRF2m sqNSCLC Monotherapy single arm N~
Slide 21: KEAP1/NRF2 Mutations Are Found Across Solid Tumors
KEAP1/NRF2 Mutations Are Found Across Solid Tumors Future development will be explored across additional tumor types to benefit additional patients Histology KEAP1 mutation frequency NRF2 mutation frequency Total mutation frequency NSCLC adeno 19% 2% 21% NSCLC squamous 12% 15% 27% Bladder 3% 9% 12%
Slide 22: Mivavotinib: SYK inhibitor for hematologic malignancies
Mivavotinib SYK inhibitor for hematologic malignancies
Slide 23: Mivavotinib Overview
Mivavotinib Overview Mivavotinib is a SYK inhibitor with single-agent clinical activity and best-in-class potential in NHL Recent preclinical data identify NHL with MyD88 or CD79 mutations as particularly vulnerable to SYK inhibition2 Preliminary mivavotinib data suggests early signal in NHL patient
Slide 24: SYK Activation in MYD88 or CD79 Mutant NHL
SYK Activation in MYD88 or CD79 Mutant NHL is Essential For Proliferation and Survival BCR pathway-addicted NHL tumors are dependent on NFkB activation for growth and survival In MyD88-mutated lymphomas, SYK associates with the myddosome, and activates NFkB In lymphomas with a constitutively active
Slide 25: DLBCL and Waldenstrom's Patients Have MyD88/CD79 Mutations
Significant Number of DLBCL and Waldenstrom’s Patients Have MyD88/CD79 Mutations Vulnerable to SYK Inhibition Preclinical validation MyD88/CD79m DLBCL cell lines have high levels of activated SYK and are sensitive to inhibition by SYK inhibitors DLBCL represents the most common subtype of NHL ~30% o
Slide 26: Mivavotinib Single Agent Activity In Multiple NHL Subtypes
Mivavotinib Has Single Agent Activity In Multiple Major Subtypes of NHL 40% ORR (31% ITT) across NHL1 Ph1 data show early signal in CD79m evaluable patients2: 2/3 CR 1 DLBCL, DOR 614 days 1 FL, DOR 176 days Mivavotinib Responses in NHL Subtypes1 Gordon at al. Clin Cancer Res. Jul 15;26(14):3546-3556
Slide 27: Mivavotinib Potential Best-In-Class SYK Inhibitor in DLBCL
Mivavotinib Has the Potential To Be a Best-In-Class SYK Inhibitor in DLBCL Clinically meaningful ORR and DOR in R/R DLBCL patients1 Mivavotinib in DLBCL ORR mDOR, days (range) mDOT in responding patients, days 28% (12/43) 19% CR NR (1-1182) 435.5 Gordon at al. Clin Cancer Res. Jul 15;26(14):3546-355
Slide 28: Favorable Single-Agent Safety Profile in NHL
Favorable Single-Agent Safety Profile in NHL Dose escalated from 60-120mg QD Most dose limiting AEs were asymptomatic laboratory abnormalities and reversible with interruption/reduction Overall safety profile appears favorable for further development as single agent and in combination 1.Gordon et al
Slide 29: Mivavotinib Development Strategy
Mivavotinib Development Strategy Planned Mivavotinib Trials Additional Development Plans: Generate data in Waldenstrom macroglobulinemia and other NHLs with MyD88/CD79 mutations Explore combinations with SOC agents (ibrutinib, venetoclax, CD20s) in NHL DLBCL with/without MyD88/CD79m Primary endpoint
Slide 30: Arginase Inhibitor CB-280 in Cystic Fibrosis
Arginase Inhibitor CB-280 Cystic Fibrosis, regardless of CFTR genotype
Slide 31: 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 32: CB-280 Randomized Ph1b Trial In Cystic Fibrosis
CB-280 Randomized Ph1b Trial In Cystic Fibrosis Ongoing Randomized Double Blind Ph1b Trial in CF Placebo Cystic Fibrosis N = approximately 32 ≥ 18 years old FEV1 40-90% predicted On stable regimen of CF therapies Chronic microbial infection Trial initiated July 2020 CB-280 Dose Escalation Cohorts Pr
Slide 33: Many CF Patients Continue to Have Impaired Lung Function
Many CF Patients Continue to Have Impaired Lung Function Leading to Long-term Lung Damage, Despite Recent Therapeutic Advances 1. Evaluate Pharma, 2021, WW forecast, 2026 2. Cystic Fibrosis Foundation. www.cff.org CF market size is expected to grow from ~$8B to $11B+ 1 Approximately 1,000 cases are
Slide 34: Well Positioned for Success
@CALITHERA Well Positioned for Success
Slide 35: Calithera Milestones
Interim data read outs in Q4 Data expected 4Q22-1Q23 Calithera Milestones Legacy Clinical Programs New Clinical Programs Robust Discovery Engine Telaglenastat (CB-839): KEAPSAKE interim data expected 4Q 2021 CB-280: Phase 1b interim data at North American Cystic Fibrosis Conference November 2021 Sap
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