Full Press Release Details
Blazing a New Path in Medicine R&D Day New York, NY May 26, 2022
Welcome and Introduction Arthur T Sands, MD, PhD President, CEO and
Board Director Nurix Therapeutics 2
Important Notice and Disclaimers This presentation contains statements
that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this presentation, the words "anticipate,"
"believe," "could," "estimate," "expect," "intend," "may," "outlook," "plan," "predict," "should," "will," and
similar expressions and their variants, as they relate to Nurix Therapeutics, Inc. ("Nurix", the "Company," "we," "us" or "our"), may identify forward-looking statements. All statements
that reflect Nurix's expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding our future financial or business
plans, performance, plans, prospects and strategies; future conditions, trends, and other financial and business matters; our current and prospective drug candidates; the planned timing and conduct of the clinical trial programs for our drug
candidates; the planned timing for the provision of clinical updates and initial findings from our clinical studies; the potential advantages of our DELigase platform and drug candidates; the extent to which our scientific approach and
DELigase platform may potentially address a broad range of diseases; the extent animal model data predicts human efficacy; and the timing and success of the development and commercialization of our current and anticipated drug candidates.
Forward-looking statements reflect Nurix's current beliefs, expectations, and assumptions. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no assurance that
they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause Nurix's actual activities
and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) risks and uncertainties related to Nurix's ability to advance its drug candidates, obtain
regulatory approval of and ultimately commercialize its drug candidates; (ii) the timing and results of clinical trials and preclinical studies; (iii) Nurix's ability to fund development activities and achieve development goals; (iv) the
impact of the COVID-19 pandemic on Nurix's business, clinical trials, financial condition, liquidity and results of operations; (v) Nurix's ability to protect intellectual property and (vi) other risks and uncertainties described under
the heading "Risk Factors" in Nurix's Quarterly Report on Form 10-Q for the fiscal quarter ended February 28, 2022, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking
statements. The statements in this presentation speak only as of the date of this presentation, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any
forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law. Certain information contained in this presentation relates to or is based on studies, publications, surveys and
other data obtained from third-party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified, and
makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations,
and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal estimates and research are reliable, such estimates and research have not been verified by any independent source.
Cancer Connects Us All 602,350 Deaths From Cancer in 2020 in the United
States Nurix is committed to building a patient-focused, science-driven oncology company powered by our leadership position in Targeted Protein Modulation 4
Cancer Connects Us All 602,350 Deaths From Cancer in 2020 in the United
States How can targeted protein modulation drugs make a difference, how are they differentiated? Simply stated, our drugs are designed to work when other drugs do not an important place to start 5
The War on Cancer Has a New Weapon Nurix is the Pioneer and Leader in
Targeted Protein Modulation Small Molecule Antibodies Nucleic Acid- Adoptive Cell Inhibitors Based Therapies Therapy Therapeutic Targeted Protein Modulation (TPM) Proteins Antisense, RNAi DeTIL to Increase or Decrease Gene Therapy Specific Protein
Levels CRISPR Small Molecule E3 Ligase Modulators 6
Nurix Drugs Engage Ligases for the Treatment of Cancer Targeted Protein
Modulation: TPM = TPD + TPE A Powerful Targeted Protein Cellular System Elevation (TPE) Harness ligases to decrease specific protein levels Inhibit ligases to increase specific protein levels Targeted Protein Ubiquitin is ligated to Degradation
target proteins to tag them for degradation by (TPD) the proteasome 7
Targeted Protein Modulation Addresses Key Limitations of Leading Cancer
Therapy Modalities Resistance Mutations Targeted Scaffolding Functions Inhibitors Undruggable Targets Cell Exhaustion Immunotherapy Cell Expansion Cell Persistence 8
The Evolution of Nurix Therapeutics Breakthrough Science, Breakthrough
Drugs 2009 - 2015 2015 - 2019 2019 - 2022 Groundbreaking Science Building the Platform Drive to the Clinic Assembled initial scientific team Innovated DNA encoded library Signed Gilead collaboration: collection and DELigase $45M
upfront Established biochemical platform proof-of-concept to drug a ligase Signed Sanofi collaboration: Built CBL and BTK programs $77M Upfront Signed Celgene IPO, follow-on offering collaboration $150M upfront Initiated four Phase 1 programs
NX-2127 IND NX-5948 CTA NX-1607 IND DeTIL-0255 IND 9
Nurix Is Advancing Four Wholly Owned Clinical Programs with a Deep
Pipeline of Proprietary and Partnered Novel Targets Target/ MOA Drug Program Therapeutic Area Pre-Clinical Phase 1 Phase 2 Phase 3 Delivery NX-2127 BTK-IKZF B-Cell Malignancies Oral Degrader TPD NX-5948 BTK B-Cell Malignancies Oral Degrader NX-1607
CBL-B Immuno-Oncology Oral Inhibitor TPE Adoptive Cell DeTIL-0255 Therapy Gynecologic Malignancies Ex vivo CBL-B Cell Therapy Inhibition 10
Today's Agenda Part 1 Anthony Mato, MD, MSCE Director, CLL Program,
Memorial Unmet Need in CLL Sloan Kettering Cancer Center First Targeted Protein Degradation Drugs in Hematologic Malignancies: NX-2127 & NX-5948 NX-2127: BTK Degrader With Robert J Brown, MD Immunomodulatory Activity & EVP, Head of Clinical
Development Initial Phase 1a Clinical Findings NX-2127 & NX-5948: Multiple Stefani A Wolff Market Opportunities COO, EVP of Product Development Q&A / Break 11
Today's Agenda Part 2 First Targeted Protein Elevation Drugs in
Immuno-Oncology: NX-1607 & NX-0255 CBL-B: Master of the Immune Cristiana Guiducci, PhD Response SVP, Immunology and Oncology Research NX-1607: Biomarkers that Robert J Brown, MD Light the Way EVP, Head of Clinical Development DeTIL-0255: Drug
Enhanced Michael T Lotze, MD Cell Therapy in the Clinic Chief Cellular Therapy Officer 12
Today's Agenda Part 3 The Genesis: Powerful Gwenn M Hansen, PhD Chief
Scientific Officer DELigase R&D Platform Hans van Houte Financial Snapshot Chief Financial Officer Conclusions Arthur T Sands, MD, PhD President, CEO and Board Director Q&A / Adjourn 13
The Team Conquering Cancer Arthur T Sands, MD, PhD Hans van
Houte Gwenn M Hansen, PhD Stefani A Wolff President, Chief Executive Chief Financial Officer Chief Scientific Officer Chief Operating Officer and Officer, and Board Director Executive Vice President, Product Development Cristiana Guiducci, PhD
Michael T Lotze, MD Christine Ring, PhD, JD Robert J Brown, MD Jason Kantor, PhD Senior Vice President, Chief Cellular Therapy Officer General Counsel and Executive Vice President, Executive Vice President, Immunology and Oncology Secretary Head of
Clinical Finance and Business Research Development Strategy 14
Key Messages for Today 1 2 3 We set the stage for the Resistance has We
have next breakthrough met its match positive and in immune with targeted protein exciting findings modulation oncology from the first trial of a TPD in a hematologic with more to come from malignancy our powerful platform 15
Bench-to-Bedside and Back: Addressing the unmet needs in Chronic
Lymphocytic Leukemia in 2022 Anthony R. Mato, MD, MSCE Associate Attending Director, Chronic Lymphocytic Leukemia Program Memorial Sloan Kettering Cancer Center New York, New York 16
Chronic Lymphocytic Leukemia CD5+ mature B-cell neoplasm
Peripheral blood, lymph node and bone marrow compartments Median age at diagnosis: 72 years Most common leukemia in Western countries Heterogenous clinical presentation Remarkable Basic, Translational and Clinical
Scientific Advances An era of targeted therapy for treatment of CLL Burger NEJM 2020; Image: Carrll TC and Venkataraman G, ASH Image Bank 2018 17
Era of Targeted Therapies: Two Key Pathways Targeted therapies are now
standard of care options in the front-line and relapsed/refractory settings B-cell receptor signaling: Covalent, irreversible Bruton's Tyrosine Kinase Inhibitors: ibrutinib & acalabrutinib Apoptotic Pathway: Bcl2-inhibitor venetoclax 18
Figure from Sedlarikova et al. Frontiers in Oncology 2020
Key Questions and Issues in Treating Relapsed CLL Patients What are the
unmet needs in the R/R setting? Limitations of covalent BTK inhibitors and venetoclax Limitations of noncovalent BTK inhibitors No standard of care for double-refractory disease 19
Covalent BTK inhibitors: Resistance and Intolerance Continue to be
Major Reasons for Discontinuation Even with Second Generation Agents! Clinical Trials and Real-World Data 20
7 Years of Follow-Up in the RESONATE-2 Study Overall discontinuation
rate at 7 years = 53% PFS: Ibrutinib vs Chlorambucil PFS in Patient Subgroups of Interest Efficacy Ibrutinib-treated patients had an 84% reduction in risk of progression or death Ibrutinib led to a 97% reduction in risk of PD or
death in patients with del(11q) and 80% for those without del(11q) vs chlorambucil Ibrutinib led to an 89% and 80% reduction in risk of PD or death in patients with unmutated and mutated IGHV, respectively, vs chlorambucil Barr PB, et al.
ASCO 2020. Abstract 7523. 21
Ibrutinib Discontinuation For Intolerance in the "Real World
Setting" 41% of patients discontinued ibrutinib at a median follow-up of 17 months Toxicity accounted for the majority of discontinuations (over half) in both F/L and R/R CLL patients Most common toxicities in R/R population: atrial
fibrillation 12.3%, infection 10.7%, pneumonitis 9.9%, bleeding 9%, and diarrhea 6.6% This study identified covalent BTK inhibitor intolerance as a major emerging issue in the field of CLL BTK, Bruton tyrosine kinase; CLL, chronic lymphocytic
leukemia; F/L, first line; R/R, relapsed/refractory. Mato et al Haematologica 2018;103:874-879. 22
Acquired Resistance to Covalent BTKi Majority of patients have
identified mutations in BTKC481 at the time of disease progression on ibrutinib; ~53-87% of patients Mutations also identified in PLCG2, immediately downstream of BTK BTKC481 mutations are also the main mechanism of resistance for
acalabrutinib; 69% of patients Figure from Burger et al NEJM 2020; Woyach et al NEJM 2014; Woyach et al JCO 2017; Scarfo et al EHA 2020; Ahn et al Blood 2017; Woyach et al ASH 2019; Burger Nature Communications 2016 23
Treatment of CLL After Covalent BTKi Venetoclax: oral
BCL2-inhibitor Front-line setting and relapsed setting including after cBTKi Approved as fixed-duration therapy (24 months in R/R setting) Phase II study of venetoclax in CLL patients with prior ibrutinib Median PFS only 24.7 months
Different than Murano PFS Figure from Jones et al Lancet Oncology 2018; 24 Seymour et al NEJM 2020; Fischer et al NEJM 2020
Patients on Landmark R/R Studies Were Not Treated on Chemotherapy-Free
Pathways or With Prior Novel Agents Only 9 of 921 Agent Study Name Number Median Percent on Percent treated with 1 patients (~1%) from (Control Arm) treated (range) prior modern BTK, Ven or PI3K-i therapies chemotherapy 6 landmark studies
free pathways were previously Ibrutinib RESONATE 195 3 0% 0% treated with at least (ofatumumab) (1 - 12) one BTKi, PI3Ki or venetoclax and likely Acalabrutinib ASCEND 155 1 0% 0% (investigator's choice: (1 - 8) none on a truly BR or
idela-ritux) modern Venetoclax Del 17p study 107 2 Unknown <3.7% 3.7% (n=4) chemotherapy-free monotherapy (single arm) (0 - 10) pathway Venetoclax- MURANO 194 1 Unknown 2.6% (n=5) rituximab (BR) (1 - >3) <2.6% Idelalisib- STUDY 116 110 3 0%
0% rituximab (placebo-ritux) (1 - 12) Duvelisib DUO 160 2 0% 0% (ofatumumab) (1 - 10) 25
Resistance and Intolerance Limit Covalent BTK Inhibitor Outcomes 1
Ibrutinib discontinuation from 4 prospective studies Options following covalent BTK inhibitor treatment are limited: Covalent BTK inhibitor retreatment: Only effective in the context of covalent BTK intolerance, not progression
Venetoclax: Efficacious but complicated administration PI3K Inhibitors: Limited benefit in this population and significant toxicity burden Chemoimmunotherapy: Limited benefit in this population and most current Ibrutinib
discontinuation rates at 5 years patients have already received these 1 Front line = 41% regimens 2 Relapsed/refractory = 54% 1 2 26 Woyach et al. J Clin Oncol. 2017;35:1437-1443. Burger. Leukemia 2020;34:787-7898.
Double Exposed CLL Patients The Cutting Edge of Unmet Needs in the
Management of the Double Refractory CLL Patient - Poor Survival
Outcomes! After BTKi Venetoclax: PI3Ki did not result in durable remissions and therefore is not an acceptable SOC rd in the 3 line setting in modern era Double Refractory Pts Median PFS = 4 months! Median OS = 3.6 months 28 Mato et al, CCR
2020, Lew, et al Blood Advances 2022
Noncovalent BTK Inhibitors 29
Several BTKi Options to Consider with Differences in BTKi Specificity,
MOA, and Potential for Off-target Effects Irreversible Zanubrutinib Ibrutinib Acalabrutinib Reversible Vecabrutinib Nemtabrutinib/ARQ-531 Pirtobrutinib/LOXO-305 Kaptein et al. Blood 2018;132(suppl 1):1871. 30
BTK Pretreated CLL/SLL Patient Characteristics a Characteristics N =
261 Baseline Molecular Characteristics Median age, y (range) 69 (36-88) Mutation status, n (%) Female, n (%) 84 (32) BTK C481-mutant 89 (43) Male, n (%) 177 (68) a ECOG PS , n (%) BTK C481-wildtype 118 (57) 0 138 (53) PLCG2-mutant 33 (16) 1 104 (40)
2 19 (7) High Risk Molecular Features, n (%) Median number of prior lines of systemic 3 (1-11) 17p deletion 51 (28) therapy (range) TP53 mutation 64 (37) Prior therapy, n (%) BTK inhibitor 261 (100) 17p deletion or TP53 mutation 77 (36) Anti-CD20