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slides and the accompanying oral presentation are forward looking, including those relating to Neoleukin's business, strategy, future operations, advancement of its product candidates and product pipeline, clinical development of its product
candidates, including expectations regarding timing of regulatory submissions and initiation of clinical trials, regulatory requirements for initiation of clinical trials and registration of product candidates, properties of its product candidates,
availability of data, the use and sufficiency of its cash resources and other statements containing the words "anticipate," "believe," "expect," "may," "plan," "project,"
"potential," "will," "would," "could," "continue," and similar expressions. These statements are subject to risks and uncertainties that could cause actual results and events to differ
materially from those anticipated, including, but not limited to, risks and uncertainties related to: whether results of early clinical trials or preclinical studies will be indicative of the results of future trials, the adequacy of any clinical
models, uncertainties associated with regulatory review of clinical trials; our ability to identify or acquire additional clinical candidates, our ability to obtain and maintain regulatory approval for any product candidates and the potential
safety, efficacy or clinical utility of or any product candidates; further impacts of COVID-19 on our operations; and other factors discussed in the "Risk Factors" section of the Company's Quarterly Report on Form 10-Q for the
quarter ended September 30, 2021 as filed with the Securities and Exchange Commission. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. More information about the risks and
uncertainties faced by the Company is contained in its Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, Annual Report on Form 10-K for the year ended December 31, 2020, and subsequent reports, filed with the Securities and
Leader in Therapeutic Protein Design First Program: Cancer Immunotherapy
Platform technology: computational 2018 FOUNDED protein design methods for creating de TM novo Neoleukin cytokine mimetics 2019 PUBLIC NL-201 program: highly potent, non- 2020 alpha, combined IL-2 and IL-15 receptor SEATTLE NL-201 IND WA agonist for
TM Neoleukin Progress in 2021 Moved into new headquarters in
Seattle (~33,000 sq ft) Initiated Phase 1 clinical trial in solid tumors for NL-201 Plan to initiate hematologic malignancy trial in 2022 Presented preclinical IL-2/IL-15 inhibitor molecule for inflammatory conditions
Leadership Team Priti Patel, M.D., M.S. Robert Ho Jonathan Drachman,
M.D. Chief Financial Officer Chief Medical Officer Chief Executive Officer Prior: AstraZeneca, Acerta Pharma Prior: Morgan Stanley & Co., DaVita Prior: CMO, EVP R&D, Seagen Bill Arthur, Ph.D. Carl Walkey, Ph.D. Holly Vance, J.D., Pharm.D.
Samantha Willing VP & Head of Research Senior VP, Corporate Development General Counsel Senior VP, People Prior: Seagen, Merck & Co. Prior: Postdoctoral Fellow, UW-IPD Prior: Gates Foundation Prior: Seagen, Microsoft Neoleukin
NL-201: De Novo IL-2/IL-15 Agonist Designed to retain benefits of IL-2
without drawbacks 100% non-alpha: no residual alpha subunit binding No bias toward T-regulatory or endothelial cells More potent than IL-2 and IL-15 Activates CD8+ na ve T-cells and NK cells Hydrophilic, compact, increased thermal
IL-2 Binds Strongly to Non-Target Cells, Causing Toxicity and Limiting
TM Building a Neoleukin Cytokine Mimetic in 4 Steps 1 2 4 3 Identify
Crystal Structure Shows Neo-2/15 Binding Beta/Gamma as Predicted IL-2
NL-201 Stimulates CD8 Effector T and NK Cells More Selectively Than
IL-2 NL-201 is ~330-fold and ~90-fold more selective for CD8+ T and NK cells (vs. Tregs) than IL-2, respectively Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020 1) STAT5 phosphorylation in CD8+ T cells, NK cells, and
NL-201 Stimulates Dose-Dependent CD8:Treg and NK:Treg Proliferation
NL-201: is Well Tolerated and Promotes Durable Antitumor Activity CT26:
syngeneic colon cancer model NL-201 is well-tolerated at therapeutic doses NL-201 treatment exhibits single-agent activity NL-201 promotes durable anti-tumor immunity Walkey et. al, AACR Virtual Annual Meeting II, Abstract
NL-201 Demonstrates Robust Single-Agent Activity in Multiple Tumor
Models 1) NL-201 was administered QWx2 when tumors reached ~100mm3. Tumor growth inhibition (TGI) is reported in each graph vs. control. 2) NL-201 treatment inhibited tumor growth in all models: NL-201 significantly inhibited tumor growth in models
NL-201 Shows Minimal Immunogenicity in NHPs ADAs were
detectable in: 3/10 NHPs at 5 g/kg; 1/6 NHPs at 15 g/kg; 0/10 NHPs at 50 g/kg NL-201 3 of 4 ADA+ NHPs were at or below the low positive control (LPC) level Abstract #4518, Walkey et. al, AACR Virtual Annual Meeting II, June
Similar Pharmacodynamics and Tolerability Observed in ADA+ vs ADA- NHPs
NL-201 Phase 1 Clinical Trial in Solid Tumors IV, monotherapy
in patients with relapsed or refractory solid tumors Part 1: Identify optimal dose and schedule; assess safety, PK, PD, and antitumor activity Part 2: Indication-specific expansion cohorts, including renal cell carcinoma and melanoma
NL-201: Broad Clinical Opportunity Plan to initiate a trial for
patients with heme malignancies in 2022 IL-2 and IL-15 have activity in multiple B-cell lineage preclinical models Abstract to be presented at ASH 2021 (Atlanta, GA) on antitumor activity of NL- 201 in multiple myeloma Future
opportunities to combine with checkpoint inhibitors, monoclonal antibodies, cellular therapies, and other standard-of-care agents Potential advantages of NL-201 local administration presented at SITC 2021 Neoleukin Therapeutics. All
NL-201 Turns Cold' Tumor Hot' Augments
inflammatory milieu in preclinical B16 melanoma model NL-201: increases T-cell diversity in the tumor microenvironment augments IFN and granzyme B expression in T-cells synergizes with anti-PD1 to inhibit tumor growth
NL-201 Upregulates PD-1 Expression by CD8+ T Cells NL-201
induces concentration- dependent PD-1 expression by CD8+ T cells Combining NL-201 with a checkpoint inhibitor may overcome PD-L1 mediated T cell inhibition Walkey et. Al, SITC 2020, Abstract #576, November 2020 Neoleukin Therapeutics.
NL-201 Enhances Activity of Checkpoint Inhibitors in Preclinical Models
NL-201 enhances activity of CPIs in breast and kidney cancer models Combination with NL-201 beneficial in CPI-resistant syngeneic tumors NL-201: 90 g/kg QWx2 PD-1: 10mg/kg BiWx6 p=0.0001: PD-1 + CTLA-4 vs
NL-201 + PD-1 + CTLA-4 p=0.0029: PD-1 vs NL-201 + PD-1 CTLA-4: 10gm/kg BiWx6 p=0.0006: NL-201 vs NL-201 + PD-1 + CTLA-4 p<0.0001: NL-201 vs NL-201 + PD-1 Treatment began when 3 tumors reached
Promising NL-201 Preclinical Combinations In Vivo Enhanced antitumor
activity with CAR-T cells and antibodies RAJI Lymphoma Model B16 Melanoma Model Subcurative doses of CAR-T cells combined with NL-201 achieve NL-201 + TA99 (mAb) deep tumor control and significantly improved 100% survival tumor growth inhibition
when combined NL-201 enhances intratumoral CD8:Treg ratios (~1000x vs. ~50x for IL-2) Leung et. al, AACR Annual Meeting II, Abstract #2222, June 2020 Walkey et. Al, SITC 2020, Abstract #576, November 2020 Neoleukin Therapeutics. All Rights
Intratumoral NL-201: Local and Distant Antitumor Activity with Improved
Tolerability Tolerability Tumor Outgrowth p=0.0466 2500 p=0.0081 Vehicle IT (R) Vehicle (R) 100 Vehicle IT (L) p=0.0184 Vehicle (L) 20 10 g IV (R) 2000 10 g IV (R) p=0.0036 10 g IV
(L) 10 g IV (L) 2 g IT (R) 1500 2 g IT (R) 2 g IT (L) 10 g IT (R) 0 2 g IT (L) 50 10 g IT (L) 1000 10 g IT (R) 10 g IT (L) 500 -20 0 0 9 16 23 30 37 9 16 23 30 37 44 51 58 65 Study Day Study Day
CT26 syngeneic tumor model with bilateral tumor implants IT (R only) or IV NL-201 administered q7dx2 10 mcg IV exceeded 20% weight loss in some mice Tatalick et al, SITC 2021, Abstract #898, November 2021 Neoleukin
TM Neoleukin Cytokine Mimetics are Hyperstable and Easily Modified Able
to withstand extreme conditions Able to adjust half-life or tune affinity Can use with targeting domain to improve biodistribution Can be conditionally activated in the tumor microenvironment Can be modified to make cytokine antagonists for
Neo-5171: A computationally designed de novo protein inhibitor of IL-2
and IL-15 signaling Potent inhibitor of CD8 T-cell proliferation and IFN- production Resistant to proteases and low pH Less impact on T-regulatory cells R. Swanson et. al. Am. Coll Rheum. (ACR) 2021; Abstract 1438, Nov
Neo-5171-Fc prolongs survival in a preclinical model of graft-vs-host
disease (GVHD) Immunodeficient NSG mice were irradiated and received 10 million human PBMC, Day -1 Intraperitoneal dosing with Neo-5171- Fc q3d, beginning on Day 0 Mice were euthanized when experiencing >20% body weight loss
De Novo Split Technology - Conditionally Active IL-2 Mimetic Neo-2/15
Part-A Neo-2/15 Part-B Cell signaling (murine CTLL2 cells) Neo-2/15 Part A Part B Reconstituted Neo-2/15 Part A + B IL2-R IL2-R Quijano-Rubio et. Al., AACR Virtual Annual Meeting II, Abstract #1075, Jun/2020 26 Neoleukin
Targeted Split Neo-2/15 Increases Therapeutic Window PBS
PDL1-Neo-2/15 (0.43 nmol) Untargeted-Part A + Untargeted-Part B (8 nmol) PDL1-Part A + PDL1-Part B (8 nmol) Notes: 1) C57BL/6J mice bearing B16 PDL1Hi melanoma cells in flank. 2) All groups were co-treated biweekly with Ta99 mAb
(150 g/mice) 3) Targeted Neo-2/15 variants and Part-A fusions administered i.p.; Part-B fusions administered s.c. opposite flank of tumor Quijano-Rubio et. Al., AACR Virtual Annual Meeting II, Abstract #1075, Jun/2020 Neoleukin
Functional De Novo Proteins Better Therapies by Design 2020 2019
Article | Published: 4 December 2020 Scientific founders are world leaders in de novo protein design Technology originated at University of Washington Institute for Protein Design Exclusive license obtained for
De Novo Platform Potential - COVID-19 NL-CVX1 - de novo ACE2
decoy: SARS-CoV-2 uses ACE2 as a receptor to Binds to SARS-CoV2 spike protein gain access to and infect cells Inhibits viral infection in vitro Designed, tested, optimized in ~10 weeks Spike protein ACE2 NL-CVX1 Spike protein
NL-CVX1 - De Novo Protein Decoy De novo design of potent and
Financial Highlights & Upcoming Milestones Financial $154.9
million cash & cash equivalents as of September 30, 2021 Cash and cash equivalents expected to fund operations into 2H 2023 1 42.4M common shares outstanding and 12.7M pre-funded warrants Upcoming Milestones Expect to
release NL-201 interim phase 1 data in 2022 Plan to initiate phase 1 heme malignancy trial for NL-201 1 Warrants to purchase common shares 1:1 with an exercise price of $0.000001 as of September 30, 2021. Neoleukin Therapeutics. All
Improving on nature. Designing for life.