Purple Biotech Ltd.

Regulatory Filings • Oct 9, 2024

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 October 2024

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 October 9, 2024, Purple Biotech Ltd. (the "Company" or the "Registrant") is announcing that it 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 October 2024

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.

October 9, 2024 PURPLE BIOTECH LTD.

By: /s/ Lior Fhima

Lior Fhima Chief Financial Officer

Forward-looking Statements and Safe Harbor

Certain statements in this presentation that are forvard-looking and not are frovant-looking statements within the meaning of the sab hardor provisions of the Private Securities Litigation Ac of 1995. Such forward-looking statements include, but are not satements of historical fact, and may be identified by words schi a "believe", "expec", "hiend", "plan", "nond", "scel", "arget", "will", "project", "torecas", "continu" or "anticipate" or wainitors of thes words of thes words of thes words o other comparable works or by the fact that these sticity to historial maters. You should not plane under eliance on these forward-looking statements, witch are not guarantees of fiture performance. For aurent view, expectations, belief or intentions with respet to fitter events, and are subject to a number of assumption, involve known and unknown risk, many of vil as well as uncertainies and other factors that may cause our actual results, performance or activerenents o be significanty different from any fiture resuls, performance or actived by the forward-looking statements. Imprant factors that could cause or contribue to such differences include, anong ofers, risks relating to: the plans, strangement for future opentions; product development for NT2 9, CM24 and M1240; the process by which such sath sage therapenic candidates could potentially lead to and subject to hights significant risks, particularly with respect to a joint development collaboraion; the fat drug development and commercialization invest legroces with uncertain outcome; our ability or successfuly develop and commercialize our pharmacedited products, the expense, length, progress and esals, the impact of any changes in regulation that could affect the pharmacutical industry; the diffically in receiving the diffically in recei regulatory approvals necessary in order to comments the U.S. Food and Drug Administration or any other applicable regulato of plarmaceutical products; the regulatory environment and regimes in the countries in which ve operate; the uncertainly surrounding the actual nurset reception to our pharmacutival products one cleared for market the introducion of competing products; patents obtained by competitors; dependence on the effectivers of on patent and other protections for interior of obtain, maintain and defend issued patents; the commencement of any patent interference or millingener or infingenent action agai patents, and ou ability to preval, obtainers in any such actor; and the exposure to lingation, including pation; the inpect the inpect the inpect the inpect the inpect of the economic, publical and security situation in Isreel, the U.S. and other countries in which we nay generals for our products on our business, and other factors that are discussed in our Amul Repor on Form 20-F or the year ended December 31, 2023 and in our of Excharge Commission ("SE"), including on cautionary discussion of risk Fielos" in our Registration Statenens and Amal Reports. These are factors that we believe could case our actual results to diffe materialy for expected results. Other fised could also adversely affect us. Any forward-looking statencen in this press relese spels only as of the date which i is made. We diselaim any intention or oblighting to purch-boking statement or other information contained beein, whether as a result of new information, future events or otherwise, except as required by applicable law. Your to consult any additional disclosures we make in our reports o the SEC's which are wailable 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

• · Multiple data read-outs expected in 2024
• · Two First-in-Class clinical stage drugs
• · A preclinical tri-specific immuno-engagers platform
• · Lean & global operation
• o Cash runway into 3Q25

Purple Biotech (NASDAQ/TASE: PPBT)

As of June 30, 2024

• ADS Outstanding: 29.0 M .
• Cash Balance: \$7.3 M
• Additional \$2 M raised in July 2024

Strong position to reach short and mid term value creating clinical data catalysts

A pipeline dedicated to advancing oncology therapies

Advancing First-in-Class Oncology Therapies

CM24: an a-CEACAM1* mAb

Lead indication: Pancreatic Ductal Adenocarcinoma (PDAC)

*Carcinoembryonic Antigen Cell Adhesion Molecule

CM24: a new multi-functional CEACAM1 inhibitor

CM24 MOA (#1) lmmune check point inhibitor

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

1 NETs in the primary tumor Cape

IL-B, IL-1B. HMGB1, ------

• · 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.)
• in distant organs 2 NETs in local invasion CM24 CCAM1 - 3 NETs in the circulation rystem ССАМТ · 120 CM24 00 4NETs promote tumor-associated thrombosis Sustained inflammation Cancer cell Dormant cancer cell (C Neutrophil Activated endothelial cell JAN NETs Activated platelet > ECM Platelet CM24 ceacam1 (6)NETs activate dormant cancer cells

5) NETs in the extravasation step

IRPLE

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

tastatic Progression of Colon Carcinoma. J Immunol. 2020; ted from 'Chen, Q et al. Cancers 2021, 13, 2832'); Royes RF, et ol. Neutrophil Extractived CFACMI co Putative Thergeutic Taget to Torget to Torget to Torget to

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

CM24 binds to CEACAM1 on NETs CM24 Inhibits NET-Induced CM24-Nivo treatment significantly reduced the migration of CEACAM1 expressing enhanced NET levels in patient's serum cancer cells 70% CID1 PRE- CID1 EOI CID1 EOI CID15 PRE- C1D15 EOI DOSE 1.5HB Level of MPO in patient serum 8,000 7,0000 (% of Pre-treatment) cells/ 6.000 AUCo24 (migrating cancer 5,000 4,000 3,000 2,000 p = 0.034 1.00 p = 0.037 No treat No treat Isotype CM24 C1D1 = Cycle 1 Day 1; EOI = End of CM24 Infusion; C1D15 = Cycle 1 Day 15 No NETs with NETs CM24 (red Melanoma cell line

· CM24 binds to CEACAM1 on NETs , inhibits NET-induced cancer cell migration, and reduces NET levels in patient's serum

• · 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

Large Market Opportunity in Pancreatic Cancer

• Pancreatic Cancer accounts for ~60K new cases/year in the US alone; with a 5-year relative survival rate of 12%
• Immuno-oncology approaches have been limited to patients with high microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H)
• · 5-year overall survival rate with chemotherapy in 2nd line patients is 3%4
• Two main interchangeable regimens are used worldwide in 2nd line:
  • Gemcitabine/Nab-paclitaxel³: OS 7.9 months, PFS 4.3 months (weighted average)
  • Irinotecan (or Nal-IRI)/5FU/LV4: OS 6.2 months, PFS 3.1 months

CM24 opportunity in PDAC

• · CEACAM1 expression correlates with poor prognosis in Pancreatic cancer2
• · Preclinical data support significant synergy of CM24 with currently marketed IO therapies;
• Combining nivolumab with CM24 in a clinical collaboration with Bristol Myers Squibb; Purple Biotech retains all worldwide rights to CM24

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2. Collected del minders (2020). Contembrion in electric (cit electric control control control.com (00.02.20/mind.org.et/1202020/0000. doi:10.1177/1758835920905408 4. Waref-Nan A, Haber R, Selection in netatatic patcedic ance: Find overly in and states in the and characterists of tongerm surviors. Eu Lance. 2009,000 (ipis.2008.200

Phase 2 Combination Study Design (NCT04731467)

OS rate @ 6 & 12 months, PFS,

PFS rate @ 3 & 6 months, ORR

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

The study is conducted in 18 centers in the US, Spain & Israel

Primary endpoint :

Secondary endpoints:

OS

Top line data: 2H24

Measurement of CEACAM1 and other bio-markers is ongoing

Phase 2 interim data (cut off date - May 8, 2024) CM24+nivolumab+Nal/IRI/5FU/LV sub-study

• 31 PDAC patients were randomized to the Nal-IRI/5FU/LV- based study regimen with a median follow up of 8.3 months.
• · CM24+nivolumab+Nal/IRI/5FU/LV regimen was well tolerated
  • · Most frequent Grade≥3: diarrhea (19%), fatigue (19%) and anemia (6%).
• · Gem/nab-paclitaxel-based part impacted by informative censoring of the control arm- imbalance between the cohorts, rendering this part unsuitable for analysis; JRPLE

Characteristic	Experimental (n=16)	Control (n=15)
Age (median)	66	68
Age ≥65 (n, %)	8 (50.0)	11 (73.3)
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	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, mo)	18	18
Time from most recent disease progression (median, mo)	0.94	0.89
CR/PR/SD to prior line (%)	43.8	60.0

Phase 2 interim data (cut off date - May 8, 2024) CM24+nivolumab+Nal-IRI/5FU/LV sub-study

26% reduction in risk of death (HR=0.74) and 28% reduction in the risk of progression or death (HR=0.72)

Prolongation of 2.1 months in median overall survival and 1.9 months in median progression-free survival

• Higher objective response rate (ORR) (25% vs 7%)

• Higher disease control rate (DCR) (63% vs 40%)

• Consistent and continuous decrease in CA19-9 was observed

Phase 2 interim data (cut off date - May 8, 2024) Efficacy summary

Parameter	Experimental (n=16)	Control (n=15)
OS (mo, median; 95% Cl)	7.72 (4.00-8.11)	5.62 (3.22 -7.89)
OS HR (95% CI)	0.74 (0.31-1.77)
6 mo OS (%)	52.7	38.9
PFS (mo, median; 95% CI)	3.8 (1.8-5.0)	1.9 (0.9-3.6)
PFS HR (95% CI)	0.72 (0.33-1.60)
3 mo PFS (%)	60.0	46.7
6 mo PFS (%)	19.0	10.0
ORR (%)	25.0	6.7
DCR (%)	62.5	40.0

Concordant and consistent improvement in the primary and all secondary endpoints

Phase 2 interim biomarker analysis data CM24+nivolumab+Nal-IRI/5FU/LV sub-study presented at AACR PANCREATIC 2024

• Analysis of patients with pre-dose serum MPO levels < 350 ng/ml, suggested 62% reduction in risk of death (HR-0.38) and prolongation of 3.3 months in OS. The same trend was shown for patients with CEACAM1*NET tumors.
• . Analysis of post-treatment reduction in serum MPO levels suggests potential OS benefit (HR=0.18) in patients with reduced post-treatment serum MPO < 180 ng/mL.

Translational data suggests NETs as a novel MoA and a potential biomarker for CM24-based therapy,

with the major advantage of a serum biomarker

Phase 2 interim biomarker analysis data CM24+nivolumab+Nal-IRI/5FU/LV sub-study presented at AACR PANCREATIC 2024

High CEACAM1 and Low PDL1 expession in tumors, as well as their combination, were identified as potential biomarkers suggesting improved survival;

· Analysis of patients with High CEACAM1 tumor cells (H-score>115), low CPS ≤ 1, or their combination, suggested potential reduction (45%, 65% and 90%) in risk of death (HR=0.55, 0.35 and 0.1), respectively.

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
		19

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

STATS

• 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

.8; 73,suppl 1 e566s; Naokazu Ibuki, Mazyar Ghaffari, Hadas Reuveni et al.
pez et al. Oncogene 2016;35(20):2634-44. Zhao C et al. Trends Pharmacol Mol Cancer Ther. 2014; 13( 35(20):2562-4; Flashner-Abramson,
gy 2018; 15(4): 234-248. Zi Ying et al. J Cell ladas, Levitzki Alexander
2018;119:9419-9432. ne 2016;35(20):2675-80;6Sanch

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

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

| 22 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) NT 219 ( 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 αPD1 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

60

50

40 30

20

10 0

-10

-20 -30

-40

-50 -60

-70

6

24 12 24 50 100 24 12 100 12

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

(P) (N) (N) (P) (P) (P) (N) (P) (P) (N) (N)

Best % change from baseline

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 *:

• · 15 evaluable patients (all doses 6, 12, 24, 50, 100 mg/kg)
• · Median follow-up of 9.4 months (95% Cl: 3.4-10.0)
• · Out of 7 treated with 50&100 mg/kg:
  • 2 confirmed PR
  • 3 SD .
  • ORR:29%, DCR: 71% .

* Interim data analysis, cut-off date Jan 25, 2024

In preparation of a phase 2 study of NT219 in combination with cetuximab w/wo chemotherapy in 2L R/M SCCHN

Activated IGF1R and STAT3 as potential predictive biomarkers

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

· Significant differences in the activated pIGF1R 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)

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
• · Technology 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 mitigate cytokine release syndrome and provide a wide therapeutic index
  • Carefully selected Tumor Associated Antigens allowing patient-centric development .

CAPTN-3 Platform Technology Advantages

| 31 NK cells CD 4 + / CD 8 + T cells CD 8 + NKG 2 A + T cells NK cell activation by inhibition of HLAE - NKG2A/CD94 binding CD 4 + / CD 8 + T cells activation through CD 3 binding CD8 + NKG2A + T cells double activation through CD3 binding and NKG2A - HLA - E axis blocking 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 aCD3 and o.NKG2A arms in suppressing 5T4*NCSLC Patient-Derived Explant (PDE)* at 10nM concentration

* E s wied tome explor (PDF) nive freed than he Mercer de minne ether ond innune eller morner mer her her mer mer mer der erency, mar he site stere, marke site en ene encere representing no viable cancer cells. The analysis included (celth) score of response (sResponse) using proprietary artificial intelligence (A) algorithm (Cresponse).

Cleavable capping leads to improved in vivo efficacy

• Sustained tumor regressions in TNBC xenograft model (MDA-MB-231) in CD34 engrafted humanized mice
• The Pro-Tribody, Capped-CD3x5T4xNKG2A, performed better than the uncapped variant
• · PK analysis in normal mice showed 3-fold higher exposure of the capped tribody compared to the non-capped
• · No change in body weight

* Study conditions: dose regimen-0.2mg/kg capped, equimolar 0.1mg/kg non capped, daily IP administration

Corporate highlights

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

• · Multiple data read-outs expected in 2024
• · Two First-in-Class clinical stage drugs
• · A preclinical tri-specific immuno-engagers platform
• · Lean & global operation
• . Cash runway into 3Q25

Purple Biotech (NASDAQ/TASE: PPBT)

As of June 30, 2024

• ADS Outstanding: 29.0 M .
• Cash Balance: \$7.3 M
• Additional \$2 M raised in July 2024 .

Strong position to reach short and mid term value creating clinical data catalysts

Appendix A | CM24

CEACAM1 Plays a Key Role in Cancer Biology

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

ପ୍ରଦାନ୍ତ
ସାହିତ୍ୟ 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 supports tumor vessel maturation" therapeutic target in head and neck exhaustion" squamous cell cancers" Ferri, 2020 Tsang, 2020 Shively, 2013 @ immunology Cancer Biotherapy.co.
Radiopharmaceuticals a Experimental
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 therapeutic target to prevent tumor cells through blockade of the 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

• · As of March 8th, 2022, a total of 13 patients were enrolled and 11 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) Inhibition

• · 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 Suppresses β-Catenin activity in CRC Cells and Inhibited CRC Brain Metastasis

Colon cancer LS-513 cells overexpressing IRS2 demonstrate enhanced β-catenin activity. Targeted inhibition of IRS2 by NT219 or IRS2-SH RNA, suppresses the increased ß-catenin activity and inhibit LS-513 cell viability. Combination of 5-FU and NT219 significantly inhibited the growth of CRC tumors intracranial model and extended mice survival.

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

NT219 suppresses cancer stem cell (CSC)-mediated resistance to KRAS02C inhibitors and synergizes with sotorasib to combat NSCLC

NT219 overcomes resistance to KRASG2D inhibitors and synergizes with MRTX1133 to combat pancreatic cancer

Higher sensitivity of mKRAS(G12D) resistant PDAC and MRTX133. a MRTX1133-restant PDAC clone was developed. Inhibition of mKRAS G12Dsensitive (APC-1) and resistant (ASPC1-MRTX113-R) by NT219 (2D cell prolferation) shows 8-fold lower (A). NT219 is effective both as monotherapy and in combination with MRTX1133 in colory formation assay of sensitive and resistant PDAC cell ines (B). Synergitic effect (C/cL) of NT219 and MRX1133 was URPLE 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