UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 OR 15(d) of The Securities Exchange Act of 1934
Date of Report (date of earliest event reported): August 5, 2021
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
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Item 2.02 Results of Operations and Financial Condition
On August 5, 2021, Neoleukin Therapeutics, Inc. (the “Company”) issued a press release announcing financial results for the quarter ended June 30, 2021. The full text of the press release announcing such results is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
Item 7.01 Regulation FD Disclosure
The Company has prepared investor presentation materials with information about the Company, which it intends to use as part of investor presentations. A copy of the investor presentation materials to be used by management for presentations is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.
The information in this current report on Form 8-K and in Exhibits 99.1 and 99.2 attached hereto is being furnished, but shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (“Exchange Act”), and is not incorporated by reference into any filing of the Company under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Item 9.01 Financial Statements and Exhibits
(d) Exhibits
| Number | Description | |||||||
| 99.1 | ||||||||
| 99.2 | ||||||||
| 104 | Cover Page Interactive Data File (formatted as Inline XBRL) | |||||||
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
Date: August 5, 2021
Neoleukin Therapeutics, Inc.
By: /s/ Robert Ho
Name: Robert Ho
Title: Chief Financial Officer
Neoleukin Therapeutics Announces Second Quarter 2021 Financial Results & Provides Corporate Update
SEATTLE, Washington, August 5, 2021 – Neoleukin Therapeutics, Inc., “Neoleukin” (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, today announced financial results for the second quarter ended June 30, 2021 and provided a midyear corporate update.
“Our progression to a clinical stage company is a significant milestone, and we remain focused on execution of our clinical development strategy and pipeline expansion as we advance and explore the potential of our de novo protein technology platform,” said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin.
Recent Updates
NL-201
NL-201 is Neoleukin's lead de novo protein therapeutic candidate, designed to mimic the therapeutic activity of natural cytokines IL-2 and IL-15, while potentially reducing the toxicities associated with high-dose IL-2.
In May 2021, Neoleukin announced dosing of the first patient in a Phase 1 trial of NL-201. The Phase 1 study, underway at clinical sites in the U.S. and Australia, is enrolling patients with advanced, relapsed, or refractory solid tumors. Patients will receive NL-201 as intravenous monotherapy to assess safety, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. While certain factors, including COVID-19, have had an impact on site activation for our Phase 1 trial of NL-201, we are accelerating site start-up activities to increase the pace of enrollment. Interim data from the ongoing systemic Phase 1 trial of NL-201 is currently anticipated in 2022.
In addition, Neoleukin is assessing plans for a local administration study of NL-201 while prioritizing the NL-201 systemic trial. Management will update timing for future trials as appropriate.
NL-CVX1
NL-CVX1 is a de novo protein that binds to the spike protein of SARS-CoV-2, the virus that causes COVID-19 and blocks infection of human cells. The design and characterization of NL-CVX1 in under three months underscores the speed and versatility of Neoleukin's de novo protein platform.
In June 2021, in response to the evolving COVID-19 therapeutic landscape, including the widespread availability of effective vaccines, Neoleukin suspended plans to advance this research program into clinical trials.
Other Research Updates
Neoleukin has multiple research projects underway evaluating the applications of de novo protein technology to develop agonists and antagonists of immune pathways. Neoleukin currently plans to discuss its de novo protein pipeline during the second half of 2021.
Summary of Financial Results
Cash Position: Cash and cash equivalents totaled $164.2 million as of June 30, 2021, compared to $192.6 million as of December 31, 2020.
Based upon current internal infrastructure and pipeline initiatives, Neoleukin believes it has sufficient cash to fund operations into 2023.
R&D Expenses: Research and development expenses for the second quarter of 2021 increased to $9.8 million from $4.8 million for the second quarter of 2020. The increase was primarily due to increased expenses incurred from IND-enabling and clinical trial activities related to Neoleukin's lead product candidate, NL-201, and in connection with the advancement of other Neoleukin technologies.
G&A Expenses: General and administrative expenses for the second quarter of 2021 increased to $5.3 million from $4.9 million for the second quarter of 2020. The increase in general and administrative expenses was primarily due to increases in personnel-related costs as Neoleukin continues to grow its operations. The increase was partially offset by higher costs incurred in the second quarter of 2020 associated with the termination of its Vancouver, Canada office lease.
Net Loss: Net loss for the second quarter of 2021 was $15.1 million compared to a net loss of $9.7 million in the second quarter of 2020.
About Neoleukin Therapeutics, Inc.
Neoleukin is a biopharmaceutical company creating next generation immunotherapies for cancer, inflammation and autoimmunity using de novo protein design technology. Neoleukin uses sophisticated computational methods to design proteins that demonstrate specific pharmaceutical properties that provide potentially superior therapeutic benefit over native proteins. Neoleukin’s lead product candidate, NL-201, is a combined IL-2 and IL-15 agonist designed to improve tolerability and activity by eliminating the alpha receptor binding interface. For more information, please visit the Neoleukin website: www.neoleukin.com.
Safe Harbor / Forward-Looking Statements
This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the therapeutic properties and potential of the company’s de novo protein design technology, the results of the clinical trial for NL-201, expectations regarding cash forecasts, and planned clinical and development activities and timelines. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references to future periods. These statements are subject to numerous risks and uncertainties, including risks and uncertainties related to the company’s cash forecasts, the company’s ability to advance its product candidates, the receipt and timing of potential regulatory submissions, designations, approvals and commercialization of product candidates, the timing and results of preclinical and clinical trials, the timing of announcements and updates relating to the company’s clinical trials and related data market conditions and further impacts of COVID-19, that could cause actual results to differ materially from what Neoleukin expects. Further information on potential risk factors that could affect Neoleukin’s business and its financial results are detailed under the heading “Risk Factors” in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Neoleukin undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
Contacts:
Media
Julie Rathbun
206-769-9219
jrathbun@neoleukin.com
Investors
Solebury Trout
Alexandra Roy
617-221-9197
aroy@soleburytrout.com
NEOLEUKIN THERAPEUTICS, INC.
Condensed consolidated balance sheet data
(In thousands of U.S. dollars)
| June 30, | December 31, | ||||||||||
| 2021 | 2020 | ||||||||||
| Assets | |||||||||||
| Cash and cash equivalents | $ | 164,235 | $ | 192,556 | |||||||
| Other current assets | 3,261 | 1,966 | |||||||||
| Non-current assets | 19,527 | 15,997 | |||||||||
| Total assets | $ | 187,023 | $ | 210,519 | |||||||
| Liabilities | |||||||||||
| Current liabilities | $ | 7,584 | $ | 7,889 | |||||||
| Non-current liabilities | 12,368 | 11,414 | |||||||||
| Total liabilities | 19,952 | 19,303 | |||||||||
| Stockholders' equity | 167,071 | 191,216 | |||||||||
| Total liabilities and stockholders' equity | $ | 187,023 | $ | 210,519 | |||||||
NEOLEUKIN THERAPEUTICS, INC.
Condensed consolidated statements of operations
(In thousands of U.S. dollars, except per share and share amounts)
| Three Months Ended June 30, | Six Months Ended June 30, | ||||||||||||||||||||||
| 2021 | 2020 | 2021 | 2020 | ||||||||||||||||||||
| Operating expenses | |||||||||||||||||||||||
| Research and development | $ | 9,824 | $ | 4,843 | $ | 19,506 | $ | 10,341 | |||||||||||||||
| General and administrative | 5,300 | 4,926 | 10,566 | 8,499 | |||||||||||||||||||
| Total operating expenses | 15,124 | 9,769 | 30,072 | 18,840 | |||||||||||||||||||
| Other income (loss), net | (5) | 23 | (7) | 452 | |||||||||||||||||||
| Net loss | $ | (15,129) | $ | (9,746) | $ | (30,079) | $ | (18,388) | |||||||||||||||
| Net loss per common stock – basic and diluted | $ | (0.27) | $ | (0.20) | $ | (0.55) | $ | (0.37) | |||||||||||||||
| Basic and diluted weighted average common shares outstanding | 55,026,404 | 49,392,533 | 54,985,639 | 49,280,492 | |||||||||||||||||||
August 5, 2021 Exhibit 99.2
© Neoleukin Therapeutics. All Rights Reserved Forward Looking Statements 2 Certain of the statements made in these 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 June 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 June 30, 2021, Annual Report on Form 10-K for the year ended December 31, 2020, and subsequent reports, filed with the Securities and Exchange Commission. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
© Neoleukin Therapeutics. All Rights Reserved Leader in Therapeutic Protein Design First Program: Cancer Immunotherapy 2018 FOUNDED 2019 PUBLIC NL-201 program: highly potent, non- alpha, combined IL-2 and IL-15 receptor agonist for cancer immunotherapy Platform technology: computational protein design methods for creating de novo NeoleukinTM cytokine mimetics NASDAQ: NLTX 2020 IND SUBMISSION 3 SEATTLE WA NL-201 2021 CLINICAL TRIALS FPI
Functional De Novo Proteins Better Immunotherapies by Design • Scientific founders are world leaders in de novo protein design • Technology originated at University of Washington Institute for Protein Design, led by David Baker, PhD • Exclusive license obtained for commercialization of NL-201 and other de novo protein assets 4 2019 2020 Article | Published: 4 December 2020 © Neoleukin Therapeutics. All Rights Reserved.
© Neoleukin Therapeutics. All Rights Reserved. Neoleukin Progress in 2021 • Initiated Phase 1 clinical trial for NL-201 • Announced hiring Priti Patel, MD as Chief Medical Officer • Occupied new lab and headquarters in Seattle, WA • ~90 FTE; added expertise in CMC and Clinical • Continuing to build our pipeline and technology 5 TM
© Neoleukin Therapeutics. All Rights Reserved. Carl Walkey, Ph.D. Senior VP, Corporate Development Prior: Postdoctoral Fellow, UW-IPD Priti Patel, M.D., M.S. Chief Medical Officer Prior: AstraZeneca, Acerta Pharma Jonathan Drachman, M.D. Chief Executive Officer Prior: CMO, EVP R&D, Seattle Genetics Robert Ho Chief Financial Officer Prior: Morgan Stanley & Co., DaVita Samantha Willing VP, People Prior: Seattle Genetics, Microsoft Holly Vance, J.D., Pharm.D. General Counsel Prior: Gates Foundation Strategic Investment Fund Leadership Team 6
© Neoleukin Therapeutics. All Rights Reserved. NL-201: De Novo IL-2/IL-15 Agonist Designed to retain benefits of IL-2 without drawbacks 7 Source: Silva et al. Nature, 565, 186-191 (2019) α β γ hIL-2Neoleukin-2/15 No bias toward T-regulatory or endothelial cells Hydrophilic, compact, increased thermal stability More potent than IL-2 and IL-15 Activates CD8+ naïve T-cells and NK cells 100% non-alpha: no residual alpha subunit binding
© Neoleukin Therapeutics. All Rights Reserved. IL-2 Binds Strongly to Non-Target Cells, Causing Toxicity and Limiting Efficacy 8 α β γ β γ IL-2 Off-Target Cells Effector Cells Toxicity & Less Efficacy Antitumor Activity IL-2IL-2
© Neoleukin Therapeutics. All Rights Reserved. Building a Neoleukin Cytokine Mimetic in 4 Steps 9 Develop an accurate structural model of the target Identify regions of intermolecular contact Design an idealized topology Assign optimal amino acid sequence 1 2 3 4 TM
© Neoleukin Therapeutics. All Rights Reserved. Crystal Structure Shows Neo-2/15 Binding Beta/Gamma as Predicted 10 IL-2 RECEPTOR ALPHA IL-2 RECEPTOR BETA IL-2 RECEPTOR GAMMA IL-2 Neo-2/15 IL-2 RECEPTOR BETA IL-2 RECEPTOR GAMMA 14% conserved sequence Source: Silva et al. Nature, 565, 186-191 (2019)
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Stimulates CD8 Effector T and NK Cells More Selectively Than IL-2 11 • NL-201 is ~330-fold and ~90-fold more selective for CD8+ T and NK cells (vs. Tregs) than IL-2, respectively 0. 00 01 0. 00 1 0. 01 0. 1 1 10 10 0 1, 00 0 1,500 2,000 2,500 3,000 Treatment (nM) M ea n p S TA T 5 CD8 Signaling IL-2 NL201 11X 0. 00 01 0. 00 1 0. 01 0. 1 1 10 10 0 1, 00 0 1,500 1,750 2,000 2,250 2,500 2,750 Treatment (nM) NK Signaling 3.1X 0. 00 01 0. 00 1 0. 01 0. 1 1 10 10 0 1, 00 0 2,000 3,000 4,000 5,000 Treatment (nM) Treg Signaling 31X 1) STAT5 phosphorylation in CD8+ T cells, NK cells, and Tregs was measured by flow cytometry using PBMCs from 10 healthy human donors. Proliferation was evaluated using Ki67. Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Stimulates Dose-Dependent CD8:Treg and NK:Treg Proliferation More Potently Than IL-2 12 0 0.3 1.0 3.0 10 30 0 1 2 3 4 5 6 7 Treatment (ng/ml) % K i6 7+ C D 8: Tr eg CD8:Treg Proliferation IL-2 NL-201 *** **** **** *** 0 0.3 1.0 3.0 10 30 0 5 10 15 20 25 30 Treatment (ng/ml) % K i6 7+ N K :T re g NK:Treg Proliferation **** **** 1) NL-201 vs IL-2: * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001 Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
© Neoleukin Therapeutics. All Rights Reserved. NL-201 is Well Tolerated and Promotes Durable Anti-tumor Activity 13 • NL-201 is well-tolerated at therapeutic doses • NL-201 treatment exhibits single-agent activity • NL-201 promotes durable anti-tumor immunity 1) Study in a checkpoint inhibitor-resistant CT26 colon cancer murine model. 0 7 14 21 28 35 0 1000 2000 3000 Study Day Tu m o r V o lu m e (m m 3 ) Re-Challenge Naive Treated 9 16 23 30 -5 0 5 10 15 20 25 30 Study Day % B o d yw ei g h t C h a n g e Tolerability Vehicle NL-201 ** 9 16 23 30 37 44 51 58 65 72 79 0 25 50 75 100 Study Day % T u m o rs < 10 00 m m 3 Tumor Growth Inhibition 6/15 (40%) tumor-freeNL-201 aPD-1 aPD-L1 Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Demonstrates Robust Single-Agent Activity in Multiple Tumor Models 14 PBS NL-201 0 1000 2000 3000 4000 Tu m o r V o lu m e (m m 3 ) Hepa1-6 (Liver) Day 24 90% TGI (p<0.0001) PBS NL-201 0 1000 2000 3000 4000 Tu m o r V o lu m e (m m 3 ) LL/2 (Lung) Day 35 64% TGI (p<0.0001) PBS NL-201 0 1000 2000 3000 4000 MC38 (Colon) Day 21 88% TGI (p<0.0001) PBS NL-201 0 1000 2000 3000 4000 EMT-6 (Breast) Day 28 62% TGI (p<0.001) PBS NL-201 0 1000 2000 3000 4000 CT26 (Colon) Day 21 78% TGI (p<0.001) PBS NL-201 0 1000 2000 3000 Pan02 (Pancreatic) Day 52 60% TGI (p<0.01) PBS NL-201 0 1000 2000 3000 4000 H22 (Liver) Day 18 77% TGI (p<0.0001) PBS NL-201 0 1000 2000 3000 4000 Renca (Kidney) Day 23 53% TGI (p<0.01) PBS NL-201 0 1000 2000 3000 4000 5000 A20 (Lymphoma) Day 26 77% TGI (p<0.001) PBS NL-201 0 1000 2000 3000 4000 B16F10 (Melanoma) Day 18 34% TGI (p=0.01) PBS NL-201 0 1000 2000 3000 4000 5000 RM-1 (Prostate) Day 20 71% TGI (p<0.0001) PBS NL-201 1000 2000 3000 4000 B16BL6 (Melanoma) Day 22 28% TGI (p=0.008) 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 that are typically refractory to anti-PD-1 checkpoint inhibitors. Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Shows Minimal Immunogenicity in NHPs 15 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 1 2 3 4 5 6 7 8 9 10 100 1000 10000 100000 Animal # A ss ay S ig n al ( A U ) D29- D29+ D43- D43+ D57- D57+ HPC MPC LPC NC 5ug/kg 15ug/kg 50ug/kg • ADAs were detectable in: 3/10 NHPs at 5µg/kg; 1/6 NHPs at 15µg/kg; 0/10 NHPs at 50µg/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 2020
© Neoleukin Therapeutics. All Rights Reserved. Similar Pharmacodynamics and Tolerability Observed in ADA+ vs ADA- NHPs 16 Adapted from Abstract #4518, Walkey et. al, AACR Virtual Annual Meeting II, June 2020 Pre 24 h 3d 5d 7d Pre 24 h 3d 0 20 40 60 80 100 % K i6 7+ C D 8+ T C el ls (% o f to ta l C D 8+ ) CD8+ Proliferation (5mg/kg) 1st Dose 5th Dose ADA- ADA+ Pre 24 h 3d 5d 7d Pre 24 h 3d 0 20 40 60 80 100 CD8+ Proliferation (50mg/kg) 1st Dose 5th Dose Pre 24 h 3d 5d 7d Pre 24 h 3d 0 20 40 60 80 100 CD8+ Proliferation (15mg/kg) 1st Dose 5th Dose
© Neoleukin Therapeutics. All Rights Reserved NL-201 Phase 1 Clinical Trial 17 ● IV, monotherapy in patients with advanced, relapsed or refractory solid tumors ● Multiple schedules and dose levels to assess safety, PK, PD, and antitumor activity ● Indication-specific expansion cohorts, including renal cell carcinoma and melanoma ● Trial will be conducted at multiple sites in Australia and North America ● Targeted enrollment up to 120 patients ● Interim data expected in 2022
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Upregulates PD-1 Expression by CD8+ T Cells 18 Walkey et. Al, SITC 2020, Abstract #576, November 2020 • 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
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Enhances Activity of Checkpoint Inhibitors in Preclinical Models 19 • NL-201 enhances activity of CPIs in breast and kidney cancer models • Combination with NL-201 beneficial in CPI-resistant syngeneic tumors 0 7 14 21 28 35 42 0 20 40 60 80 100 Study Day % S u rv iv in g EMT-6 (Breast) Vehicle aPD-1 NL-201 NL-201 + aPD-1 7/9 tumor-free 0 7 14 21 28 35 42 0 20 40 60 80 100 Study Day % S u rv iv in g Renca (Kidney) Vehicle aPD-1 + aCTLA-4 NL-201 NL-201 + aPD-1 + aCTLA-4 5/9 tumor-free p=0.0001: ⍺PD-1 + ⍺CTLA-4 vs NL-201 + ⍺PD-1 + ⍺CTLA-4 p=0.0006: NL-201 vs NL-201 + ⍺PD-1 + ⍺CTLA-4 p=0.0029: ⍺PD-1 vs NL-201 + ⍺PD-1 p<0.0001: NL-201 vs NL-201 + ⍺PD-1 NL-201: 90µg/kg QWx2 ⍺PD-1: 10mg/kg BiWx6 ⍺CTLA-4: 10gm/kg BiWx6 Treatment began when tumors reached ~90mm3
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Potently Expands CAR-T Cells and Promotes Antitumor Activity 20 Subcurative doses of CAR-T cells combined with NL-201 induce deep tumor control and achieve 100% survival. NL-201 greatly enhances intratumoral CD8: Treg ratios (approximately 1000x compared to 50x for IL-2). Leung et. al, AACR Virtual Annual Meeting II, Abstract #2222, June 2020
© Neoleukin Therapeutics. All Rights Reserved. NL-201 Enhances Activity of Tumor-Targeting Antibodies in Multiple Preclinical Models 21 Walkey et. Al, SITC 2020, Abstract #576, November 2020 NL-201 + TA99 significantly improved tumor growth inhibition compared to TA99 or NL-201 alone
© Neoleukin Therapeutics. All Rights Reserved. Neoleukin Cytokine Mimetics are Hyperstable and Easily Modified 22 Able to withstand extreme conditions Able to adjust half-life or tune affinity Can be conditionally activated in the tumor microenvironment Can be modified to make cytokine antagonists for inflammatory and autoimmune diseases Can use with targeting domain to improve biodistribution Source: Silva et al. Nature, 565, 186-191 (2019) TM
© Neoleukin Therapeutics. All Rights Reserved. De Novo Split Technology - Conditionally Active IL-2 Mimetic 23 Cell signaling (murine CTLL2 cells) N o rm a liz e d p S TA T 5 M F I Neo-2/15 Part A Part B Part A + B Quijano-Rubio et. Al., AACR Virtual Annual Meeting II, Abstract #1075, Jun/2020 Neo-2/15 Part-A Neo-2/15 Part-B Reconstituted Neo-2/15 IL2-Rβ IL2-RƔ
© Neoleukin Therapeutics. All Rights Reserved. Targeted Split Neo-2/15 Increases Therapeutic Window 24 % W ei g h t c h an g e Weight change D12 Days after tumor inoculation Percent Survival Notes: 1) C57BL/6J mice bearing B16 PDL1Hi melanoma cells in flank. 2) All groups were co-treated biweekly with Ta99 mAb (150µg/mice) 3) Targeted Neo-2/15 variants and Part-A fusions administered i.p.; Part-B fusions administered s.c. opposite flank of tumor PBS ⍺PDL1-Neo-2/15 (0.43 nmol) Untargeted-Part A + Untargeted-Part B (8 nmol) ⍺PDL1-Part A + ⍺PDL1-Part B (8 nmol) Quijano-Rubio et. Al., AACR Virtual Annual Meeting II, Abstract #1075, Jun/2020
© Neoleukin Therapeutics. All Rights Reserved. De Novo Platform Potential – COVID-19 25 ACE2 NL-CVX1 - de novo ACE2 decoy: • Binds to SARS-CoV2 spike protein • Inhibits viral infection in vitro • Designed, tested, optimized in ~10 weeks Cell Virus Spike protein Cell Virus ACE2 Spike protein SARS-CoV-2 uses ACE2 as a receptor to gain access to and infect cells NL-CVX1
© Neoleukin Therapeutics. All Rights Reserved. NL-CVX1 – De Novo Protein Decoy 26 De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2 T. W. Linsky et. al. Science. 10.1126/science.abe0075 (2020)
© Neoleukin Therapeutics. All Rights Reserved. Financial Highlights 27 ● $164.2 million cash & cash equivalents as of June 30, 2021 ● Cash and cash equivalents expected to fund operations into 2023 ● 42.3M common shares outstanding and 12.7M pre-funded warrants1 1 Warrants to purchase common shares 1:1 with an exercise price of $0.000001 as of June 30, 2021.
Improving on nature. Designing for life.