Purple Biotech Ltd.

Regulatory Filings • Mar 19, 2025

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549

FORM 6-K

Report of Foreign Private Issuer Pursuant to Rule 13a-16 or 15d-16 of the Securities Exchange Act of 1934

For the month of March 2025 Commission File Number: 001-37643

PURPLE BIOTECH LTD.

(Translation of registrant's name into English)

4 Oppenheimer Street, Science Park, Rehovot 7670104, Israel (Address of principal executive offices)

Indicate by check mark whether the registrant files or will file annual reports under cover Form 20-F or Form 40-F.

Form 20-F ☒ Form 40-F ☐

On March 18, 2025, Purple Biotech Ltd. (the "Company" or the "Registrant") has made available an updated Company Presentation on its website. A copy of the updated Company Presentation is attached hereto as Exhibit 99.1 and may be viewed at the Company's website at www.purple-biotech.com.

Exhibit

99.1 Purple Biotech Corporate Presentation March 2025

Incorporation by Reference

This Report on Form 6-K, including all exhibits attached hereto, is hereby incorporated by reference into each of the Registrant's Registration Statement on Form S-8 filed with the Securities and Exchange Commission on May 20, 2016 (Registration file number 333-211478), the Registrant's Registration Statement on Form S-8 filed with the Securities and Exchange Commission on June 6, 2017 (Registration file number 333-218538), the Registrant's Registration Statement on Form F-3, as amended, originally filed with the Securities and Exchange Commission on July 16, 2018 (Registration file number 333-226195), the Registrant's Registration Statement on Form S-8 filed with the Securities and Exchange Commission on March 28, 2019 (Registration file number 333-230584), the Registrant's Registration Statement on Form F-3 filed with the Securities and Exchange Commission on September 16, 2019 (Registration file number 333-233795), the Registrant's Registration Statement on Form F-1 filed with the Securities and Exchange Commission on December 27, 2019 (Registration file number 333-235729), the Registrant's Registration Statement on Form F-3 filed with the Securities and Exchange Commission on May 13, 2020 (Registration file number 333-238229), the Registrant's Registration Statement on Form S-8 filed with the Securities and Exchange Commission on May 18, 2020 (Registration file number 333-238481), each of the Registrant's Registration Statements on Form F-3 filed with the Securities and Exchange Commission on July 10, 2020 (Registration file numbers 333-239807 and 333-233793), the Registrant's Registration Statement on Form S-8 filed with the Securities and Exchange Commission on April 4, 2022 (Registration file number 333-264107) and the Registrant's Registration Statement on Form F-3 filed with the Securities and Exchange Commission on March 23, 2023 (Registration file number 333-270769), the Registrant's Registration Statement on Form F-3, as amended, originally filed with the Securities and Exchange Commission on December 8, 2022 (Registration file number 333-268710), the Registrant's Registration Statement on Form F-1, as amended, originally filed with the Securities and Exchange Commission on October 30, 2023 (Registration file number 333-275216) and the Registrant's Registration Statement on Form F-1, filed with the Securities and Exchange Commission on July 22, 2024 (Registration file number 333-280947), to be a part thereof from the date on which this report is submitted, to the extent not superseded by documents or reports subsequently filed or furnished.

1

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

March 18, 2025 PURPLE BIOTECH LTD.

By: /s/ Gil Efron

Gil Efron Chief Executive Officer

Forward-looking Statements and Safe Harbor

Certain statements in this presention that are forvacle of historial fact are forward-ooking statements within the meaning of the safe harbor povisions of the Private Securities Libertion Reform A.o of 1995. Such forvarly include, but age not linited on strements of Listances of Listancial for any be identified by words scharged as "beleve", "super", "intend", "phond", "toold", "might", "seek", "treess", "conime" or "anticipat" or their negatives or vannions of these words of these words of other coupande works or by the fact these strents to historial maters. You should not place under eviance on these forwards. Which are not guarantees of fittle performance. For current view, expectations, beliefs or intentions with respect to finter event, and are subject to a uniber of assumptions, involve laown and uslarsm risks, many of which as well as well as uncertaintes and other factors that results, performance or achievements to be significanty different from any finterenents expensed or implied by the forward-looking statenents. Important factors that could cause or contibute to such differences include, anong obest relaing to the plans, stransgener for fitter opentions; product development for NT219, CM24 and M1240; the process by which such and y sage therapentic candidates could potentially lead to and subject to hights significant isks, particularly with respect to a joint development collaboration, the fact that doug development and commercialization in west a process with unertain outcome; our ability to successfuly develop and commercial podes; the expense, length, progess and results of any changes in regultion and legistation that could affect the pharmacentical industry, the difficulty in receiving the regulatory approvals necessary in order to comments, the difficulty of predicing actions of the U.S. Food and Drug Administration or any other applicable regulator of phamaceuted products; the reglatory environment and ceams in the counters in the counters in which we operate; the uncertainty surrounding the actual maker reseption to our plamaceuical products one cleared for maket; the introduction of competing products; patents obtained by competitor; dependence of our patents and other products; our ability to obtain and defend issued patents; the commencement of any patent interference or infinisenent or informent action against on patents, and ou ability to prevail, obhaine and the exposue to lingtion, and the exposue to lingtion, and or regulatory actions; and or regulatory actions; the inget of the economic, political and security situation in Isael, the U.S. and other countries in which we may yourse or our products or our products or our products or our business, are discussed in our Annual Report on Form 20-7 of the now of the U.S. Securies and Exchange Commission ("SE"), including on cautionary discussion of risks Fectors" in on Registration Statements and Annual Reports. These are factors that we believe could cause our actual results of differ materialy from expected results these we lised could also adversely affect us. Any forward-boking statener in this press celese speaks only as of the date which it is made. We disclaim any intention or obligation to public or revise any forward or other information contained heein, whether as a result of new information, fiture events or otherwise, except as required by applicable any You and any additional discosses we make in our reports o the SEC, which are analable on the SEC's website, https://www.sec.gov.

Corporate highlights

Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need

• Two First-in-Class clinical stage drugs
• A preclinical tri-specific immuno-engagers platform
• Lean & global operation
• Cash runway into mid 2026 .

Purple Biotech (NASDAQ/TASE: PPBT)

As of December 31, 2024

• ADS Outstanding: 2.6 M .
• Cash Balance: \$8.2 M

Well positioned to advance next clinical milestones

A pipeline dedicated to advancing oncology therapies

Advancing First-in-Class Oncology Therapies

CM24: an α-CEACAM1* mAb

Significant opportunity in multiple large indications with unmet medical need

Clinical POC achieved

CM24: POC of a potential CEACAM1-targeting therapy

Attractive new target	· CEACAM1 is overexpressed on certain tumor cells and infiltrating immune cells • CEACAM1 is a part of the Neutrophil Extracellular Traps (NETs) structure
Demonstrated mechanism of action	• CM24 increases T cell and NK cells-mediated cytotoxicity against tumors · CM24 binds to CEACAM1 on NETs and inhibits NET-related activities • CM24 shows benefits in combination with immuno-oncology treatments
Poc Clinical efficacy	• Favorable safety profile in monotherapy and in combination with nivolumab • Positive P2 efficacy data • Serum CEACAM1 and MPO potential biomarkers demonstrated clinically significant results • Additional potential biomarkers identified such as CEACAM1* tumor cells and CPS
Sizable market potential	Large opportunities to leverage the MoA in multiple indications (Lung, Colon, Breast, Gl etc.) · Significant unmet medical need in pancreatic ductal adenocarcinoma (PDAC), most common form of pancreatic cancer

CM24 MOA (#1) lmmune modulation

CM24 MOA (#2) Blocks NET oncogenic potential through CEACAM1 blockage

• Neutrophil extracellular traps (NETs) are web-like structures involved in:

  • Tumor immune evasion (1, 3)

  • Tumor progression (1, 2, 6)

  • Metastasis (2, 3, 5, 6)

  • Cancer-associated thrombosis (4)

• · CEACAM1 is a part of the NET structure
• NETs are present in various types of cancers (pancreatic, breast, GI, etc.)

JRPLE

CM24 binds to CEACAM1 on NETs, inhibiting NET-related activities

astatic Progression of Colon Carcinoma. J Immunol. 2020; ted from 'Chen, Q et al. Cancers 2021, 13, 2832', Rayes RF, et al. Neutrophil Extracted to CACAM1 os o Putrive Theropextive Theropextive Theropextive Theropextiv

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CM24 MOA (#2 cont.) Blocks NET oncogenic potential thru CEACAM1 blockage

. CM24 binds to CEACAM1 on NETs , inhibits NET-induced cancer cell migration, and reduces NET levels in patients' sera

• · MPO (myeloperoxidase) is a NET marker, an integral part of the NET structure
• In the randomized P2, NET-related MPO was found as a potential predictive biomarker for CM24-based treatment

Significant opportunity in multiple large indications with unmet medical need

• CEACAM1 is upregulated in different cancer indications: >90% in Colon and Bladder and >70% in Lung, Gastric, breast, and other 1
• · Elevated levels of neutrophil extracellular traps (NETs) have been observed in various cancers such as Lung, Breast, gastrointestinal cancers, and others2,3
• · Strong scientific rationale and supporting clinical data

CM24 opportunity in PDAC

• · Pancreatic Cancer accounts for ~60K new cases/year in the US alone; with a 5-year relative survival rate of 12. The 5-year overall survival rate with chemotherapy in 2nd line patients is 3%4
• · Two main interchangeable regimens are used worldwide in 2™ line with limited benefit, OS ranging from 6 to 8 months5,6
• CEACAM1 expression correlates with poor prognosis in Pancreatic cancer7
• Clinical and preclinical data support synergy of CM24 with currently marketed IO therapies

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Phase 2 Combination Study Design (NCT04731467)

A study of CM24 in combination with nivolumab* plus chemotherapy in patients with PDAC in the 2nd line

18 centers in the US, Spain & Israel

Each cohort was a separate study Patients were randomized after assignment to chemo regimen

A substantial rate of early discontinuation in the control arm of the gemcitabine/ Abraxane regimen created an imbalance between the two arms, leading to informative censoring. Consequently, the efficacy analysis of this regimen was deemed biased and uninterpretable.

Measurement of biomarkers: CEACAM1. NET marker (Myeloperoxidase-MPO), PDL1

Primary endpoint : OS

Secondary endpoints:

OS rate @ 6 & 12 months, PFS, PFS rate @ 3 & 6 months, ORR

Phase 2 final analysis

Intent to Treat (ITT) Population demographics and patient characteristics

	Nal-IRI/5FU/LV
Characteristic	Experimental (n=16)	Control (n=15)
Age (median)	66.0	68.0
Male (n, %)	10 (62.5)	8 (53.3)
Female (n, %)	6 (37.5)	7 (46.7)
Race/ white (n, %)	15 (93.8)	14 (93.3)
BMI (median)	23.4	23.1
0 ECOG (n, %)	5 (31.3)	3 (20.0)
1	11 (68.8)	12 (80.0)
Time from initial diagnosis (median, m)	17.8	17.6
Time from most recent disease progression (median, m)	1.0	1.0
BOR CR/PR to prior line (%)	6.3	33.3
BOR SD to prior line (%)	37.5	26.7
BOR CR/PR/SD to prior line (%)	43.8	60.0
Tumor M1 stage at study entry: N (%)	14 (87.5) 14 (93.3)
Pancreaticoduodenectomy	0 (0.0)	1 (6.7)

Phase 2 final analysis

Safety Population the most frequent related Grade ≥3 TEAEs

Grade ≥3 TEAE	Nal-IRI/5FU/LV
Neutropenia Diarrhea Fatigue Anaemia Nausea Vomiting Thrombocytopenia	Experimental (n=16) N (%)	Control (n=15) N (%)
	2 ( 12.5)	0 ( 0.0)
	4 ( 25.0)	1 ( 6.7)
	2 ( 12.5)	0 ( 0.0)
	0 ( 0.0)	0 ( 0.0)
	1 ( 6.3)	0 ( 0.0)
	1 ( 6.3)	0 ( 0.0)
	0 ( 0.0)	0 ( 0.0)
White blood cell count decreased	0 ( 0.0)	0 ( 0.0)

( The CM24+nivolumab+Nal/IRI/5FU/LV regimen was well tolerated )

Phase 2 final analysis CM24+nivolumab+Nal-IRI/5FU/LV sub-study

19% reduction in risk of death (HR=0.81) and 25% reduction in the risk of progression or death (HR=0.75)

Prolongation of 2.3 months in median overall survival and 1.9 months in median progression-free survival

Phase 2 final analysis CM24+nivolumab+Nal-IRI/5FU/LV sub-study

• Higher objective response rate (ORR) (25% vs 6.7%)

• Higher disease control rate (DCR) (62.5% vs 46.7%)

• Consistent and continuous decrease in CA19-9 was observed

% change in tumor size

Median CA 19-9 levels

Phase 2 final analysis-Efficacy summary

CM24+nivolumab+Nal-IRI/5FU/LV sub-study

Parameter	Nal-IRI/5FU/LV
	Experimental	Control
OS (median, m; 95% Cl)	7.92 (4.14, 8.02)	5.55 (3.45, 7.56)
OS HR (95% CI)		0.81 (0.38,1.71)
6m OS rate (%)	53.6	46.7
PFS (median, m; 95% CI)	3.91 (1.84, 5.13)	1.97 (0.95, 3.78)
PFS HR (95% CI)		0.75 (0.35, 1.61)
3m PFS rate (%)	66.7	46.7
6m PFS rate (%)	26.7	13.3
ORR (%)	25.0	6.7
DCR (%)	62.5	46.7

Concordant and consistent improvement in the primary and all secondary efficacy endpoints

Phase 2 final biomarker analysis data Results for pre-treatment serum CEACAM1 level

Statistically significant results in patients with pre-treatment serum CEACAM1 level between 6K to 15K:

• 79% reduction in the risk of death (HR = 0.21) and > 90% reduction in the risk of progression or death (HR < 0.1)

• Prolongation of 5.1 months in median overall survival and 2.9 months in median progression-free survival

Phase 2 final biomarker analysis Results for pre-treatment serum CEACAM1 or NET marker MPO levels

Statistically significant results in patients with defined pre-treatment serum CEACAM1 or MPO levels in the study:

• 61% reduction in risk of death (HR = 0.39) and 72% reduction in the risk of progression or death (HR=0.28)

• Prolongation of 2.4 months in median overall survival and 2.2 months in median progression-free survival

Phase 2 final biomarker analysis data Results for CEACAM1 and PDL1 levels in tumors

Statistically significant results for patients with High CEACAM1 (H-score>100) and Low PDL1 (CPS ≤ 1 ) expression in tumors:

• 90% reduction in risk of death (HR = 0.1) and 81% reduction in the risk of progression or death (HR = 0.19)

• Prolongation of 4 months in median overall survival and 2 months in median progression-free survival

CM24 path forward Novel MoA-directed opportunity

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Advancing First-in-Class Oncology Therapies

NT219: A Small Molecule Dual Inhibitor of IRS 1/2 and STAT3

Lead indication: Recurrent/Metastatic Head & Neck Cancer (SCCHN)

NT219, a new solution to improve treatment outcome for cancer patients

Innovative MOA	• NT219 is a First-in-Class, small molecule dual inhibitor of IRS1/2 and STAT3 • Covalently binds to IRS1/2 and leads to their degradation · Affects both the tumor and the TME · Suppresses cancer stem cells
Robust preclinical package	· Outstanding efficacy in various PDX models in monotherapy and in combination · Uniquely positioned to tackle resistance to cancer treatment such as EGFRi, MAPKi and ICI
Clinical Stage	· No DLTs in monotherapy or in combination · Early clinical activity demonstrated • RP2D determined at 100 mg/kg, Phase 1 concluded. Phase 2 initiation 1H25
Broad Market Potential	• Opportunity to establish a Standard of Care in 2L r/m SCCHN patients ം Multiple market upsides in combination with major cancer treatments • NT219 is the only IRS inhibitor available for clinical investigations
		22

NT219 blocks 2 critical signalling pathways at once

IRS1/2

• · Scaffold proteins, mediating mitogenic, metastatic, angiogenic and antiapoptotic signals from IGF1R, IR, IL4R and other oncogenes, overexpressed in multiple tumors
• Regulates major survival pathways such as the PI3K/AKT, MEK/ERK and WNT/βcatenin
• · Activated as a feedback response to anti-cancer therapies
• IRS plays an important role in promoting a tumor-protective microenvironment, by mediating upregulation of TAMs and CAFs

STAT3

• Well-established transcription factor associated with the tumorigenic phenotype
• · STAT3 is broadly hyperactivated in many cancers, promoting proliferation, survival, angiogenesis and metastasis
• · STAT3 pathway is required for TGFBinduced EMT and cancer cell migration and invasion
• STAT3 is a critical player in tumor immune evasion, suppressing immune stimulators and enhancing immunosuppressive factors

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NT219 restores sensitivity to EGFRi in PDX models

Lung Cancer Non-small cell lung cancer (NSCLC)

Exon 19 deletion EGFR and T790M, biopsy of bone marrow metastasis, patient previously progressed on afatinib and osimertinib

Head & Neck Cancer

Recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) metastasis, patient progressed on chemoradiation, several chemotherapies and pembrolizumab

Osimertinib 5 mg/kg, NT219 65 mg/kg, mean tumor volume at the end point, 3 mice/group;

Treatments on days 0, 3 and 10, cetuximab - 1mg/mouse, 3 mice/group; PBMCs (1.4M cells/mouse) were injected on day 6 ** p<0.01, * p<0.02 based on one-way ANOVA with post hoc Tukey's HSD test

| 25 NT219 re - sensitizes PD1 - refractory model 6 8 10 12 14 16 18 20 22 0 500 1000 1500 2000 Control α-PD-1 NT219 NT219+α-PD-1 Days post tumor challenge T u m o r v o l u m e ( m m 3 ) Days following tumor challenge PD 1 - resistant melanoma cells (FACS analysis) PDL1 expression (MFI) NT219 ( M) treatment in culture 0 1 10 NT 219 + PD 1 reverse resistant tumors NT 219 induces PDL 1 expression (n=10) (n=10) (n= 10 ) (n=10) * Collaboration with Prof. Bareli and Prof. Curran, M.D. Anderson cancer center ; presented at AACR 2023

NT219 combination with «PD1 achieves a profound reprograming of the TME

First Market Opportunity

Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN)

Targeting the unmet medical need

• SCCHN is the 6th most common cancer type ; 175k new cases/year are expected by 2024
• 1L standard of care has shifted from chemotherapy towards immuno-oncology + chemotherapy
• < 20% of R/M SCCHN patients respond to Pembrolizumab
• ・Market size forecasted to >\$5b in 2030

Phase 1 dose escalation in combination with cetuximab: Well tolerated, target exposure reached, patient's responses observed

• No DLTs reported, NT219 was well tolerated as monotherapy and in combination with cetuximab
• Dose-proportional increase in AUC and Cmax values
• Human Equivalent Dose exposure was reached at 50 mg/kg
• Target engagement demonstrated in patients' biopsies
• · RP2D determined at 100 mg/kg

Post-treatment

Phase 1 Dose Escalation (cont.): Anti-tumor activity at target exposure level, 2 confirmed responses in SCCHN patients

Efficacy overview of monotherapy arm:

· 20 evaluable patients (all doses): 2 PR (confirmed-GEJ, unconfirmed-PDAC), 5 SD

Efficacy overview of combination arm in SCCHN patients*:

• · 16 evaluable patients (all doses 6, 12, 24, 50, 100 mg/kg)
• ·
• Out of 8 treated with 50&100 mg/kg:
  • 2 confirmed PR
  • 3 SD .
  • ORR:25%, DCR: 62.5% ●

Numbers under horizontal line designate NT219 dose in mg/kg; P = HPV positive; N = HPV negative

Advancing phase 2 study in combination with cetuximab or pembrolizumab in R/M SCCHN in collaboration with Uni. Of Colorado

Activated IGF1R and STAT3 as potential predictive biomarkers

Biomarker analysis at the 50mg/kg dose of NT219 with cetuximab:

• Significant differences in the activated plGF1R and pSTAT3 were revealed in the 2 responders (PR) compared to the 2 non-responders (PD)

Advancing First-in-Class Oncology Therapies

CAPTN-3: Conditionally-Activated Tri-Specific Antibody Platform

Lead candidate: IM1240 (CD3x5T4xNIKG2A)

CAPTN-3 Platform A novel mechanism of action tri-specific antibody

• Multi-specific biologics is an expanding class of drugs getting a lot of interest in the industry
• · After initial success in hemato-oncology, new formats are being investigated in solid tumors
• Platform displays several distinctive features:
  • Dual engagement of T cells and NK cells to mount an optimal anti-tumoral immune response
  • A tumor-restricted activation through a cleavable capping system designed to provide a wide therapeutic index
  • Plug & Play Carefully selected Tumor Associated Antigens (TAAs) allowing patient-centric development. portfolio includes several assets, targeting different receptors and TAA

CAPTN-3 platform technology advantages

▪ Molecule size similar to mAb (~170 kDa)

αTAA arm: ■ Tumor Associated Antigen Targeted activation against tumor cells 33

| 34 Unleashing both innate and adaptive immune systems

POC: αNKG2A arm contributes substantially to tumor cell killing and synergizes with the CD3 Arm

• . Tribody induces cytotoxicity at pM EC50 against NSCLC A549 cells
• Up to 20-fold more potent than the bi-specific CD3x5T4 . Cell killing validated on multiple 5T4* cell lines (MDA-
• MB-231, HCT116, NCI-H226)

Synergistic effect of the αCD3 and αNKG2A arms in suppressing . 5T4*NCSLC Patient-Derived Explant (PDE)* at 10nM concentration

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In vivo efficacy - significant and sustained tumor regression

• Effective cleavage leads to significant tumor regression by both capped and non-capped tribodies (p<0.0001). .
• No tumor recurrence observed
• Frequency of administration QOD

TNC MD-MB-231 cells were s. inoculated 11 with PMCs on day of required or equimblar dose 1.7 mg/kg (capped 1240) till day 24, 8 mice per group, follow up 20 days follow up 20 treatment completion

lmproved safety profile: Cytokine release is 5T4-dependent and suppressed by the cap

· The capped variant vs the non capped, showed a decreased IFNy release > 150-fold (Safety factor #1). · In the absence of 5T4-expressing cancer cells the non-capped variant showed a decreased IFNy release "50-fold (Safety factor #2).

| 38 5T4: a Novel Target in Oncology 5 T 4 is highly expressed on certain tumors and correlates with poor prognosis Am J Cancer Res 2018;8(4):610 - 623 www.ajcr.us /ISSN:2156 - 6976/ajcr0074519 5 T 4 is a Tumor Associated Antigen prevalent to several large indications Opportunity of patient stratification strategy ( 5 T 4 + )

Corporate highlights

Purple Biotech identifies promising first-in-class drug candidates to treat cancers with high unmet medical need

• Two First-in-Class clinical stage drugs
• A preclinical tri-specific immuno-engagers platform
• Lean & global operation
• Cash runway into mid 2026 .

Purple Biotech (NASDAQ/TASE: PPBT)

As of December 31, 2024

• ADS Outstanding: 2.6 M .
• Cash Balance: \$8.2 M

Well positioned to advance next clinical milestones

Appendix A | CM24

CEACAM1 Plays a Key Role in Cancer Biology

03 | IMMUNO-ONCOLOGY 02| IMMUNE CELLS/ 01| ADHESION IMMUNE EXCLUSION Tsuzuki, 2020 Blumberg, 2015 Horst, 2011 ୍ତି ।

ପ୍ରଦାନ ପ୍ରଦାନ Oncogene nature "CEACAM1 creates a pro-angiogenic "Immune-checkpoint molecules on "CEACAM1 regulates tumor microenvironment that regulatory T-cells as a potential TIM-3-mediated tolerance and therapeutic target in head and neck supports tumor vessel maturation" exhaustion" squamous cell cancers" Ferri, 2020 Tsang, 2020 Shively , 2013 @ Immunology Cancer Biotherapy.co. Cell Research "Neutrophil extracellular trap-"[Blockade] enhances natural "CEACAM1 regulates Fas-mediated associated CEACAM1 as a putative killer cell cytotoxicity against apoptosis in Jurkat T-cells via its tumor cells through blockade of the therapeutic target to prevent interaction with в-catenin" metastatic progression of colon inhibitory CEACAM1 / CEACAM5 carcinoma" immune checkpoint pathway"

CM24 Reduces Tumor Burden & Synergetic with α-PD-1

Phase 1 Dose Escalation Interim Results CM24 is Safe and Well Tolerated in Combination with Nivolumab

Study Design

• patients were evaluable for DLT determination (8 PDAC, 2 CRC and 1 PTC).
• 9 patients had received 2 prior regimens for metastatic disease, 2 . patients had one previous line.

Safety

• No DLTs were observed across all dose levels; no Grade 4 . AEs or treatment-related deaths have been reported.
• Grade 3 AEs were noted in 6/13 patients (46%). .

		Grade
AE Term	Total	1	2	3	4/5
Diarrhea	5	4		1
Abdominal pain	4	1	3
Fever	4	2	2
Headache	4	3	1
Fatigue	4	4
Nausea	3	1	2
Creatinine increased	3	2	1
Hypokalemia	2			2
Dyspnea	2	1		1
Constipation	2	2
Cough	2	2
Abdominal pain aggravated	1			1
Alkaline phosphatase increase	1			1
Atrial flutter	1			1
C-Diff Colitis	1			1
GI bleed	1			1
Leukocytosis	1			1
Small bowel obstruction	1			1

CM24 Phase 1 Combination Study (NCT04731467) Demographics

In the Phase 1 part, patients with indicated refractory cancers were administered CM24 at 10, 15, and 20mg/kg q2w and nivolumab 480mg q4w.

• · The primary objective of this part was to evaluate safety, tolerability, pharmacokinetics and determine the RP2D
• Safety was assessed according to CTCAE v5 and preliminary anti-tumor activity was assessed by the investigators according to RECISTv1.1 using CT/MRI
• CM24 and CEACAM1 measurements in serum, biopsy specimens, . and TILs, as well as tumor and TILs PD-L1 levels are being determined

As of March 8th, 2022, a total of 13 patients were enrolled and 11 patients were evaluable for dose-limiting toxicity (DLT) determination (8 PDAC, 2 CRC and 1 PTC)

. . 9 patients had received 2 prior regimens for metastatic disease and 2 patients had one previous line.

Demographics of patients treated with CM24 (10, 15, 20mg/kg) in combination with nivolumab (480mg)

Median age, years (range)		65 (49-76) Prior Lines of Therapy, n (%)
Sex, n (%)		1	2 (18%)
Male	5 (45%)	2	9 (82%)
Female	6 (55%)	Diagnosis , n (%)
Ethnicity, n (%)		Pancreatic cancer	8 (73%)
Not Hispanic or Latino	10 (91%)	Papillary Thyroid cancer	1 (9%)
Hispanic or Latino	1 (9%)	Colorectal cancer	2 (18%)
Race, n (%)		Median Time from Initial Diagnosis months (range)	23 (11-73)
White	10 (91%)	ECOG, n (%)
Black or African American	1 (9%)	0	7 (64%)
		1	4 (36%)

Confirmed Partial Response in a 3L PDAC Patient

Patient Profile

• . 65 y/o female, pancreatic cancer
• · 2 prior lines of treatments: FOLFIRINOX and gemcitabine/nab-paclitaxel
• . Post Whipple Procedure
• . Patient had a germline NF1 VUS, with MSI-S and PDL-1 IHC 2+ and 5% staining
• Confirmed Partial Response: after initial treatment, the patient had a Partial Response of 40%, with a definite reduction of the para-tracheal adenopathy and liver lesions and 58% reduction in CA19-9 levels
• . Under treatment for 6 months, still under monitoring.

SCREENING FIRST VISIT - PREDOSE 2 MONTH VISIT -

PREDOSE

CM24 Phase 1 Dose Escalation Results Encouraging data in 2L/3L Pancreatic Ductal Adenocarcinoma (PDAC) patients

Study Results

14 patients were evaluable for efficacy:

• . Best overall response included 1 Partial Response (PR) (PDAC) and 4 Stable Disease (SD) (3 PDAC and 1 papillary thyroid cancer (PTC))
• Pharmacokinetic analysis of CM24 shows exposure is dose-proportional across the 3 doses in this study
• Well tolerated with no Dose Limiting Toxicities (DLTs) and no grade ≥ 4 Adverse Events (AEs)
• Median Overall Survival 4.5 months (95% Cl 2.0-11.1) for 11 PDAC patients

Appendix B | NT219

Novel MOA: IRS Degradation By NT219 Blocking IGF1R-AKT Pathway¹

Novel MOA Signal Transducer and Activator of Transcription 3 (STAT3) Înhibition

• · Point of convergence for numerous oncogenic signaling pathways
• · Central in regulating the anti-tumor immune response
• Broadly hyperactivated both in cancer and non-cancerous cells within the tumor ecosystem and plays important roles in inhibiting the expression of crucial immune activation regulators and promoting the production of immunosuppressive factors
• Targeting the STAT3 signaling pathway has emerged as a promising therapeutic strategy for numerous cancers

NT219 demonstrates a durable and dose-dependent suppression of STAT3 tyrosine phosphorylation, affecting both the tumor cells and the tumor microenvironment.

Selected Publications

NT219 inhibits the IRS to ß-Catenin pathway and synergizes with 5FU to suppress CRC tumor growth in mouse brain

overcomes chemo-resistance, and inhibits LS-513 cell viability and tumor growth in intracranial model.

AACR Annual Meeting, April 2021, AACR Virtual Special Conference on Epigenetics and Metabolism, Oct 2020, Ido Wolf, MD, Head of Oncology Division, Tel Awis Soursky | 54 Medical Center

RNA Sequencing| Reduced expression of IRS1, Ki67, FOXM1 & TGFb is exhibited by pancreatic cancer treated with NT219 alone and Analysis of Tumors in combination with gemcitabine Following Treatment IRS1 Ki67 (Proliferation marker) PDX model 17% Control NT219 Gemzar Gemzar Gemzar Pancreatic Cancer NT219 Gemzar Gemzar Control +NT219 +NT219 FOXM1 TGFbeta (EMT Driver) 1009 Drug Gemcitabine (Gemzar®) Control NT219 Gemzar Gemzar Control Gemzar +NT219 +NT219 | 26

NT219 suppresses cancer stem cell (CSC)-mediated resistance to KRASG2C inhibitors and synergizes with sotorasib to combat NSCLC

NT219 overcomes resistance to KRAS02D inhibitors and synergizes with MRTX1133 to combat pancreatic cancer

Higher sensitivity of mKRAS(G12D) resistant PDAC and MRTX1133. a MRTX1133-restant PDAC clone was developed. Inhibition of mKRAS G2Di sensitive (APC-1) and resistant (APCI-MRTX113-R) by NT219 (2D cell proliferation) shows 8-fold lover (C50 for the resistant cell line (A). NT219 is effective both as monotherapy and in combination with MRTX1133 in colory formation assay of sensitive and resistant PDAC cell lines (B). Synergiste effect (CrL) of NT219 and MRTX133 ws demonstrated in 2D growth (C) and in spheroid 3D growth (D) of HPAC PDAC cells.

Collaborationn with Dr. Azmi, Karmanos. Presented at AACR Annual Meeting 2024

JRPLE