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 9, 2022
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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 9, 2022, Neoleukin Therapeutics, Inc. (the “Company”) issued a press release announcing financial results for the quarter ended June 30, 2022. 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 9, 2022
Neoleukin Therapeutics, Inc.
By: /s/ Jonathan G. Drachman
Name: Jonathan G. Drachman
Title: President and Chief Executive Officer
EX-99.1
Neoleukin Therapeutics Announces Second Quarter 2022 Financial Results & Provides Corporate Update
–Company to Host Conference Call Today, August 9, 2022, at 1:30 p.m. Pacific / 4:30 p.m. Eastern -
SEATTLE, Washington, August 9, 2022 – 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, 2022 and a midyear corporate update.
“Our focus at Neoleukin is the advancement of de novo proteins to solve important therapeutic challenges and address unmet medical needs," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "We are excited to be part of a revolutionary approach to creating therapeutic proteins that are not based on native sequences. Our first programs, including our lead product candidate, NL-201, were developed using sophisticated computational algorithms combined with directed evolution in the laboratory. We have now added machine learning and neural networks to our technological approach, enabling faster, more accurate development of increasingly complex proteins. Using these new processes, we have been able to add two new cytokine mimetics to our discovery pipeline this year."
"At Neoleukin, we are excited to be testing NL-201, which we believe is the first fully de novo protein in clinical trials," said Priti Patel, M.D., Chief Medical Officer. "We are pleased to have begun testing NL-201 in combination with pembrolizumab in mid-May of this year. We believe this is just one of many potential opportunities to harness the immune activating properties of NL-201 in novel combination regimens."
NL-201 Update
Neoleukin is conducting a clinical trial of intravenous NL-201 in patients with advanced solid tumors. The trial is evaluating two different schedules and multiple dose levels in order to determine a recommended Phase 2 dose and schedule. Intermediate dose levels have been added to both schedules, which has extended the timeline to reach the anticipated Phase 2 dose. Dose escalation continues in both schedules, and Neoleukin now anticipates disclosing interim data in 2023.
In April 2022, Neoleukin announced the presentation of preclinical data at the American Association for Cancer Research (AACR) Annual Meeting, highlighting the potential for NL-201 to treat non-Hodgkin lymphoma as well as synergistic antitumor activity when NL-201 is combined with radiation therapy, including significant inhibition of tumor growth and increased survival in preclinical models.
EX-99.1
In May 2022, Neoleukin announced treatment of the first patient in a combination arm evaluating the safety and efficacy of Neoleukin’s NL-201 in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab), as part of Neoleukin’s ongoing Phase 1 trial. Up to 132 patients will be enrolled in the combination arm of the study, which is being conducted through a clinical collaboration and supply agreement with Merck (known as MSD outside the United States and Canada). The trial is assessing safety, pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Research Updates
Technology: Neoleukin's research team is actively engaged in the discovery of additional de novo cytokine mimetics as well as technological advances in order to accelerate the process from concept to proof of preclinical activity. Among these advances, the use of machine learning and neural networks have made it possible to design de novo proteins even when high-resolution structures have not yet been solved, using less compute resources and with a higher percentage of functional sequences. In addition to NL-201, Neoleukin has previously reported preclinical data for two de novo proteins: NL-CVX1, a decoy protein that mimics the human ACE2 binding site of the SARs-CoV2 spike protein and Neo-5171, an inhibitor of both IL-2 and IL-15 signaling.
Pipeline: Neoleukin is exploring an activator of T-regulatory cells for the treatment of inflammation and autoimmune diseases, a next generation IL-2/IL-15 agonist, and two additional undisclosed de novo cytokine mimetics for the treatment of cancer.
Summary of Financial Results
Cash Position: Cash, cash equivalents, and short-term investments totaled $116.5 million as of June 30, 2022, compared to $142.5 million as of December 31, 2021.
Based upon current internal infrastructure and pipeline initiatives, Neoleukin believes it has sufficient cash to fund operations through 2023.
R&D Expenses: Research and development expenses for the second quarter of 2022 increased to $11.0 million from $9.8 million for the second quarter of 2021. The increase was primarily due to increased clinical trial expenses related to NL-201.
G&A Expenses: General and administrative expenses for the second quarter of 2022 decreased to $4.9 million from $5.3 million for the second quarter of 2021. The decrease was primarily attributable to decreases in personnel-related and facility-related costs.
Net Loss: Net loss for the second quarter of 2022 was $15.7 million compared to a net loss of $15.1 million in the second quarter of 2021.
About NL-201
NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data has demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at low doses with minimal impact on immunosuppressive regulatory T cells. Furthermore, NL-201 has demonstrated both monotherapy and combination activity across a wide range of preclinical syngeneic tumor models.
EX-99.1
Conference Call Information
Neoleukin will host a conference call today to provide a second quarter corporate update and review financials. Details are as follows:
Date: August 9, 2022
Time: 1:30 p.m. Pacific / 4:30 p.m. Eastern
Toll-free: (800) 715-9871
Conference ID: 4116795
Webcast URL: http://investor.neoleukin.com/events
The archived audio webcast with slides will be available on the Investor Relations section of the Neoleukin website approximately two hours after the event and will be available for replay for at least 30 days after the event.
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 and timing 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, our ability to protect our intellectual property, the timing and results of preclinical and clinical trials, changes to laws or regulations, market conditions, geopolitical events, 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” included in Neoleukin's Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K filed from time to time with the Securities and Exchange Commission (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.
EX-99.1
Contacts:
Media
Julie Rathbun
206-769-9219
jrathbun@neoleukin.com
Investors
Solebury Trout
Alexandra Roy
617-221-9197
aroy@soleburytrout.com
EX-99.1
NEOLEUKIN THERAPEUTICS, INC.
Condensed consolidated balance sheet data
(In thousands of U.S. dollars)
| June 30, | December 31, | ||||||||||
| 2022 | 2021 | ||||||||||
| Assets | |||||||||||
| Cash, cash equivalents, and short-term investments | $ | 116,457 | $ | 142,467 | |||||||
| Other current assets | 2,028 | 1,522 | |||||||||
| Non-current assets | 18,536 | 19,274 | |||||||||
| Total assets | $ | 137,021 | $ | 163,263 | |||||||
| Liabilities | |||||||||||
| Current liabilities | $ | 9,271 | $ | 8,636 | |||||||
| Non-current liabilities | 11,042 | 11,763 | |||||||||
| Total liabilities | 20,313 | 20,399 | |||||||||
| Stockholders' equity | 116,708 | 142,864 | |||||||||
| Total liabilities and stockholders' equity | $ | 137,021 | $ | 163,263 | |||||||
EX-99.1
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, | ||||||||||||||||||||||
| 2022 | 2021 | 2022 | 2021 | ||||||||||||||||||||
| Operating expenses | |||||||||||||||||||||||
| Research and development | $ | 10,956 | $ | 9,824 | $ | 21,656 | $ | 19,506 | |||||||||||||||
| General and administrative | 4,915 | 5,300 | 9,580 | 10,566 | |||||||||||||||||||
| Total operating expenses | 15,871 | 15,124 | 31,236 | 30,072 | |||||||||||||||||||
| Loss from operations | (15,871) | (15,124) | (31,236) | (30,072) | |||||||||||||||||||
| Other income (loss), net | 183 | (5) | 197 | (7) | |||||||||||||||||||
| Net loss | $ | (15,688) | $ | (15,129) | $ | (31,039) | $ | (30,079) | |||||||||||||||
| Comprehensive income (loss): | |||||||||||||||||||||||
| Unrealized loss on available-for-sale securities | (72) | — | (72) | — | |||||||||||||||||||
| Comprehensive loss | $ | (15,760) | $ | (15,129) | $ | (31,111) | $ | (30,079) | |||||||||||||||
| Net loss per share – basic and diluted | $ | (0.28) | $ | (0.27) | $ | (0.56) | $ | (0.55) | |||||||||||||||
| Basic and diluted weighted average common shares outstanding | 55,203,709 | 55,026,404 | 55,173,789 | 54,985,639 | |||||||||||||||||||
Corporate Presentation August 2022 © Neoleukin Therapeutics. All Rights Reserved. EX-99.2
Forward Looking Statements 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, its ability to identify or acquire additional clinical candidates, its 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, supply chain disruptions, or other global economic and geopolitical events on its operations; and other factors discussed in the “Risk Factors” section and elsewhere in the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2022, Annual Report on Form 10-K for the fiscal year ended December 31, 2021, and subsequent reports 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. 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.2
© Neoleukin Therapeutics. All Rights Reserved.3 We use protein design to reinvent how therapies are created with a goal to meaningfully improve patients’ lives Neoleukin is a pioneer in de novo protein development, leveraging computational methods to create new therapies. This new approach has unlimited potential to treat human disease by improving on nature, designing for life. We are building a company with a vibrant and inclusive culture that we believe will make a meaningful impact for patients, our people and our community.
2018 2019 2020 2021 2022 FUTURE NEOLEUKIN FOUNDED Computational methods enable fully de novo protein design Scientists and technology spun out of University of Washington MERGER COMPLETED NASDAQ listing (NLTX) after merger with Aquinox More than $140M raised through merger and follow-on offering FIRST IND SUBMITTED First IND of fully de novo protein (NL-201) Neoleukin scientists create second fully de novo protein (NL- CVX1) PHASE 1 TRIAL INITIATED First patients treated with fully de novo protein Experienced drug- developers added in Clinical and Research MACHINE LEARNING Machine learning/neural network technology enables rapid drug discovery EXPAND DE NOVO PROTEIN PIPELINE Multiple fully de novo molecules expected to enter development in oncology and autoimmune diseases Innovative approaches to drug delivery, conditional activation, and affinity optimization to improve therapeutic index Neoleukin: Leader in de novo Protein Therapeutics © Neoleukin Therapeutics. All Rights Reserved.4
Leadership Team @Neoleukin Therapeutics. All Rights Reserved.5 Carl Walkey, Ph.D. Senior VP, Corporate Development P R I O R Postdoctoral Fellow, UW-IPD Priti Patel, M.D., M.S. Chief Medical Officer P R I O R AstraZeneca Acerta Pharma Jonathan Drachman, M.D. Chief Executive Officer P R I O R CMO, EVP R&D Seagen Sean Smith VP, Finance P R I O R Aptevo Therapeutics KPMG Bill Arthur, Ph.D. VP & Head of Research P R I O R Seagen Merck & Co. Donna Cochener General Counsel, SVP Legal P R I O R HomeStreet Davis Wright Tremaine
Better Therapies by Design Functional de novo proteins © Neoleukin Therapeutics. All Rights Reserved.6 2019 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 commercialization of NL-201 and other de novo protein assets
De Novo Protein Design • Amino acids are nature’s building blocks for proteins • The order they are arranged in determines how a protein folds, what it binds to, and what it does • Decades of research into protein folding, thermodynamics, and advances in computational power has resulted in the ability to design proteins that have never existed before © Neoleukin Therapeutics. All Rights Reserved.7 AMINO ACIDS PEPTIDE PROTEIN Neoleukin is leading the revolution in de novo protein therapeutics
Neoleukin™ de novo design methodology © Neoleukin Therapeutics. All Rights Reserved.8 IL-2R alpha IL-2R gamma IL-2 IL-2 IL-2R beta NL-201 NL-201 IL-2 Develop an accurate structural model of target Identify regions of intermolecular contact Design an idealized topology Assign optimal amino acid sequences 1 2 3 4 • High-resolution structural models of native ligand-receptor interactions guide design • Iterative process from multiple scientific disciplines to refine designs • Early methods focused on less complex structures
NL-201: de novo non-alpha IL-2/IL-15 agonist Potent, stable, no bias toward Tregs or endothelial cells © Neoleukin Therapeutics. All Rights Reserved.9 hIL-2Neoleukin-2/15 NL-201 is a de novo protein designed with no alpha subunit interaction and increased beta/gamma binding Source: Silva et al. Nature, 565, 186-191 (2019) 14% Conserved sequence α β γ
NL-201: Durable Antitumor Activity at Well-tolerated Doses © Neoleukin Therapeutics. All Rights Reserved.10 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 an 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 CT26 syngeneic murine colon cancer model • NL-201 is well-tolerated at therapeutic doses • Single-agent activity observed • Tumor-free mice reject CT26 upon re-challenge Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
NL-201 Demonstrates Robust Single-Agent Activity in Multiple Tumor Models © Neoleukin Therapeutics. All Rights Reserved.11 • NL-201 was administered QWx2 when tumors reached ~100mm3 • Tumor growth inhibition (TGI) is reported in each graph vs. control. • NL-201 significantly inhibited tumor growth in all models, including those that are refractory to checkpoint inhibitors 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) Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
Similar Pharmacodynamic Response in ADA+ vs ADA- NHPs © Neoleukin Therapeutics. All Rights Reserved.12 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 Walkey et. al, AACR Virtual Annual Meeting II, Abstract #4518, June 2020
NL-201: High CD8:Treg and NK:Treg Ratios at Low Concentration © Neoleukin Therapeutics. All Rights Reserved.13 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 **** **** 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
De Novo Platform Potential: COVID-19 © Neoleukin Therapeutics. All Rights Reserved.14 NL-CVX1 - de novo ACE2 decoy: • Binds to SARS-CoV2 spike protein • Inhibits viral infection in vitro SARS-CoV-2 uses ACE2 as a receptor to gain access to and infect cells ACE2 Cell Virus Spike protein Cell Virus ACE2 Spike proteinNL-CVX1 De Novo protein designed, tested, and optimized in the pre-clinical setting in ~10 weeks
Neo-5171: A computationally designed de novo protein inhibitor of IL-2 and IL-15 signaling © Neoleukin Therapeutics. All Rights Reserved.15 • Potent inhibitor of CD8 T-cell proliferation and IFN-g 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 2021 Control Neo-5171 + 1 nM IL-2 * * In presence of 30 pM aCD3
Neo-5171-Fc prolongs survival in a preclinical model of graft-vs-host disease (GVHD) © Neoleukin Therapeutics. All Rights Reserved.16 • Immunodeficient NSG mice were irradiated, received 107 human PBMC on Day -1 • Intraperitoneal dosing with Neo-5171-Fc q3d, beginning Day 0 • Mice were euthanized when experiencing >20% body weight loss • At high dose 62.5% of mice survived at study end (Day 42) R. Swanson et. al. Am. Coll Rheum. (ACR) 2021; Abstract 1438, Nov 2021
Highly Selective De Novo Treg Expander and Activator • Highly tuned CD122/CD132 activator fused to Treg-targeting domain • Potential to specifically expand Tregs for the treatment of autoimmune diseases and inflammation • Finely tuned de novo protein to achieve optimal affinity and potency for specificity and cis-activation • Demonstrated ability to drive specificity by targeting de novo cytokine mimetics © Neoleukin Therapeutics. All Rights Reserved.17 Tuned IL-2 receptor agonist Treg binding domain
Evolution of Neoleukin™ De Novo Protein Technology Accelerating speed and accuracy © Neoleukin Therapeutics. All Rights Reserved.18 • New methodology combines machine-learning (ML) based sequence design and structure prediction with high-throughput screening. • ML-based methods enable more efficient protein design with higher success rates and using a fraction of the computing power. • We can now develop from a more expanded landscape of protein topologies that were not accessible by traditional methods. Predicted Structure In Silico Validation ML-based protein design High-throughput Screening Lead Optimization Fi tn es s
Adding Machine Learning to Protein Design Building the next generation of de novo proteins New methods are required to tackle more complex topologies © Neoleukin Therapeutics. All Rights Reserved.19 4-helix bundle Some cytokine families have complex structures
De Novo Split Technology: Conditionally Active IL-2 Mimetic © Neoleukin Therapeutics. All Rights Reserved.20 Cell signaling (murine CTLL2 cells) N or m al ize d pS TA T5 M FI 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
Targeted Split Neo-2/15 Increases Therapeutic Window © Neoleukin Therapeutics. All Rights Reserved.21 • C57BL/6J mice bearing B16 PDL1Hi melanoma cells in flank • All groups were co-treated biweekly with Ta99 mAb (150µg/mice) • Targeted Neo-2/15 variants and Part-A fusions administered i.p.; Part-B fusions administered s.c. opposite flank of tumor % W ei g h t c h an g e Weight change D12 Days after tumor inoculation Percent Survival 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
Pipeline © Neoleukin Therapeutics. All Rights Reserved.22 Program Mechanism Discovery Preclinical Development Phase 1 Oncology NL-201 IL-2/15 Agonist Solid Tumors IL-2/15 Agonist Heme Malignancies Neo-202 Next-gen IL-2/15 Agonist Neo-XX De Novo Cytokine Mimetic Undisclosed Target Neo-YY De Novo Cytokine Mimetic Undisclosed Target Inflammation Neo-5171 IL-2/15 Antagonist Autoimmune / Inflammatory Conditions Neo-TRA T-reg Agonist Autoimmune / Inflammatory Conditions NL-201 is believed to be the 1st de novo protein in clinic
NL-201 Phase 1 Monotherapy Trial in Patients with 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 • Continuing to dose escalate; interim dose escalation data expected in 2023 © Neoleukin Therapeutics. All Rights Reserved.23 Intermediate doses have been approved by the DMC and are being explored. * Screening (≤28 days) Enrollment (D1) 0.1 µg/kg n≥3 0.3 µg/kg n≥3 1 µg/kg n≥3 3 µg/kg n≥3 6 µg/kg n≥3 12 µg/kg n≥3 18 µg/kg n≥3 24 µg/kg n≥3 End of Treatment Long-term Follow-up Radiological Follow-up Discontinuation prior to PD Discontinuation due to PD Tr ea tm en t P er io d Sch. A: D1 of 21D cycle (Q3W) Sch. B: D1 & D8 of 21-day cycle Part 1: Dose Escalation Part 2: Dose Expansion Renal Cell (n=30) Melanoma (n=30)
NL-201: Broad Opportunity in Cancer • Solid tumor monotherapy trial ongoing • Combination dosing with pembrolizumab began May 2022 • Heme trial initiation pending outcome of safety data in dose escalation in solid tumors • Consider future opportunities to combine with monoclonal antibodies, cellular therapies and other standard-of-care agents • Potential advantages of NL-201 local administration presented at SITC 2021 © Neoleukin Therapeutics. All Rights Reserved.24
NL-201 Turns ‘Cold’ Tumors ‘Hot’ Augments inflammatory milieu in preclinical B16 melanoma model © Neoleukin Therapeutics. All Rights Reserved.25 TCRβ Sequencing Summary Mean (range) Total T cells Unique T cells Simpson Clonality Vehicle (n=5) 1,406 (358-2,708) 445 (196-807) 0.194 (0.106-0.411) Anti-PD-1 (n=5) 2,456 (987-4,713) 464 (314-775) 0.34 (0.138-0.57) NL-201 (n=5) 2,664 (1,578-3,816) 869 (611-1,064) 0.206 (0.11-0.292) NL-201 plus anti-PD-1 (co-admin) (n=5) 2,865 (1,504-3,456) 1,042 (536-1,486) 0.128 (0.073-0.165) 0 500 1000 1500 2000 ce ll co un ts ( ce lls /m g of tu m or ) CD8+IFNg+ T cells * * ** * 0 50 100 150 200 400 600 ce ll co un ts ( ce lls /m g of tu m or ) CD4+IFNg+ Th1 cells * * * ns 0 400 800 1200 1600 ce ll co un ts ( ce lls /m g of tu m or ) CD8+GrB+ T cells * * ** NL-201 • increases T-cell diversity in the tumor microenvironment • augments IFNg and granzyme B expression in T-cells • synergizes with anti-PD1 to inhibit tumor growth Mortales et. al, SITC 2021, Abstract #716, Nov 2021 Vehicle anti-PD-1 NL-201 NL-201 + anti-PD-1 (co-admin)
NL-201 Enhances Activity of Checkpoint Inhibitors in Preclinical Models © Neoleukin Therapeutics. All Rights Reserved.26 Combination with NL-201 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
Promising NL-201 Preclinical Combinations In Vivo Enhanced antitumor activity with CAR-T cells and antibodies © Neoleukin Therapeutics. All Rights Reserved.27 Leung et. al, AACR Annual Meeting II, Abstract #2222, June 2020 Walkey et. al, SITC 2020, Abstract #576, November 2020 B16 Melanoma ModelRAJI Lymphoma Model • NL-201 combined with a subcurative dose of CAR-T cells achieve deep tumor control and 100% survival • NL-201 enhances intratumoral CD8:Treg ratios (~1000x vs. ~50x for IL-2) • NL-201 + TA99 (mAb) significantly improved tumor growth inhibition when combined
NL-201 in Hematologic Malignancies: Preclinical Data • NL-201 delays relapse in murine myeloma model following autologous stem cell transplant • NL-201 induces expansion of cytotoxic CD8 T-cells and a decrease in T-regulatory CD4 cells in the bone marrow • NL-201 treated mice had an increase in bone marrow T-cells expressing granzyme B and a decrease in the T-cell exhaustion phenotype • Planning to initiate Phase 1 trial for NL-201 in patients with hematologic malignancies based on dosing and safety data expected from solid tumor trial © Neoleukin Therapeutics. All Rights Reserved.28 Minnie et al, American Society of Hematology 63rd Annual Meeting. Abstract 1609. December 2021
Intratumoral NL-201: Local and Distant Antitumor Control with Improved Tolerability © Neoleukin Therapeutics. All Rights Reserved.29 •CT26 syngeneic tumor model with bilateral tumor implants • IT (R only) or IV NL-201 administered qWx2 •10 mcg IV exceeded 20% weight loss in some mice Mean Tumor Volume Veh ic le 2 g IT 10 g IV 10 g IT Pe rc en ta ge C ha ng e in Bo dy W ei gh t ( % ) ✱✱ ✱✱ ✱ ✱ Tolerabilitya P ro p o rt io n o f T u m o rs < 10 0 0 m m 3 (% ) Tumor Outgrowth Tatalick et al, SITC 2021, Abstract #898, November 2021
Focusing Efforts to Preserve Cash Runway Financial Highlights • $116.5 million cash, cash equivalents, and short-term investments as of June 30, 2022 • Cash and cash equivalents expected to fund operations through 2023 • 42.6M common shares outstanding and 12.7M pre-funded warrants1 Cash Runway Focus • Goal to ensure adequate runway to support achievement of NL-201 clinical milestones through 2023 • Focused operating plan around core value driving activities • Reduced personnel growth to limit expenses © Neoleukin Therapeutics. All Rights Reserved.30 1. Warrants to purchase common shares 1:1 with an exercise price of $0.000001 as of June 30, 2022.
Improving on nature. Designing for life. © Neoleukin Therapeutics. All Rights Reserved.