Purple Biotech Ltd.

Regulatory Filings • Jun 5, 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 June 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 June 4, 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 June 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) and the Registrant's Registration Statement on Form F-1 filed with the Securities and Exchange Commission on October 30, 2023 (Registration file number 333-275216), 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.

June 4, 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 forward-looking statements of historial foot are fromating of the safe transmine of the safe transmission of the Private Securities Litigation Referm Ac of 1995. Such forwards include, but are not Innice to, statements of historial from and may be identified by words such as "telleve", "stylend", "plan", "nay", "stould", "migh", "steek", "will", "project", "contine" or "anticipate" or "anticipate" or wantions of these words of these words of ober comparable words or by the fact there strently to historial matters. You should not phone under celiance on these forward-looking statements, which are not guarantees of future performance. For our current view, expectations, beliefs or intentions with respect to future events, and are subject o a number of assumption, involve hown and unknown risks, nany of which as well as uncertaintes and other factors that may cause our actual results, performance or achievements of esignificanty different from any fitter results, performance or achesed or implied by the forward-looking statements. Important factors that could cause or contribue to such differences in anong others, risks relaing to: the plans, strangement for future operations; poduct development for NT219, CM24 and M1240; the process by which such sage therapetic candidates could potentially lead o an approved is long and subject to hights signitually with respect on joint development of lact that drug development and commercialization involves with uncome; our ability o successfuly develop and commercialize our pharmaceuical poducts; the expense, length, prograss and essult of any changes in regulation and legistation that could affect the pharmaceutical industry; the difficuly in receining the regulatory appovals necessary in order to comments; the difficulty of predicting actions of the U.S. Food and Drug Administration or any other applicable of pharmacentical products; the regulatory en the health policies and regimes in the countries in which we operating surrounding the actual maker reappion to our pharmaceuical products one cleared for market the introducion of compeing products; patents obtained by competitors; dependence on the effectivers of our patent and other products; our ability to obtain, maintan and defend issued patents; the commencement of any patent interference or infingener action against our patents, and ou ability to preval, obtain or recover damages in any such action; and the exposure to liigation, andro regulatory actions; the inpact of the economic, publical and security situation in Isseel, the U.S. and other countries in which we may operate or our position of our business, and other for our products or o are discussed in our Annual Report on Form 20-7 or the year ended December 31, 2023 and in our of Exchange Commission ("SE"), including our cautionary discussion of risks and uncertains on Registration Statements and Annual Reports. These are factors that we believe could case our actual results to differ materially from expected resuls. Other fised could also adversely affect us. Any forward-looking statement in this press release speals only a of the date which i is made. We disclaim any intention or oblighting to purch-looking statement or other information contained herin, whether a a result of new information, future events or otherwise, except as required by applicable law. You actional discosures we make in our reports o the SEC, 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
• . Cash runway into 1Q25

Purple Biotech (NASDAQ/TASE: PPBT)

As of March 31, 2024

• ADS Outstanding: 26.6 M .
• Cash Balance: \$10.8 M

A pipeline dedicated to advancing oncology therapies

Advancing First-in-Class Oncology Therapies

CM24: an α-CEACAM1* mAb

Lead indication: Pancreatic Ductal Adenocarcinoma (PDAC)

*Carcinoembryonic Antigen Cell Adhesion Molecule

CM24: a new multi-functional immune checkpoint inhibitor

Attractive new target	· CEACAM1 is overexpressed on certain tumor cells and infiltrating immune cells · CEACAM1 interacts with CEACAM1 and CEACAM5 and creates a tumor-protective environment
Demonstrated mechanism of action	· CM24 increases T cell and NK cells cytotoxicity against tumors • CM24 shows benefit in combination with immuno-oncology treatments · CM24 blocks adhesion of tumor cells to Neutrophil Extra cellular Traps (NETs)
Signals of clinical efficacy	· Favorable safety profile in monotherapy and in combination with nivolumab • Interim P2 data from the Nal-IRI/5FU/LV sub-study demonstrate a reduced risk of death or progression, prolongation of OS and PFS, supported by higher ORR, DCR and decreasing CA19-9 · Potential biomarkers identified such as NETs and CEACAM1 levels on TILs Randomized Phase 2 is ongoing, last patient enrolled in Dec-23, top line data 2H24
Sizable market potential	· Significant unmet medical need in pancreatic ductal adenocarcinoma (PDAC), most common form of pancreatic cancer Strong IP position and well ahead of competitors Multiple opportunities to leverage the MoA in other clinical settings 0	6

CM24 MOA lmmune check point inhibitor & anti-metastatic activity

Merel d. J. mmorder, 2006, immonder 200, Creater et 1, M (Creer The 202, 200, 2022, Home) 2020, Arien, 202, 2019, 01: 01. Immorderers on este 2022, 2009, 01:54 a., D. C.E.CAM | 7

CEACAM1 is over-expressed in pancreatic cancer

and normal (10 cases/20 cores) tissues

Large Market Opportunity in Pancreatic Cancer

| 9

• Pancreatic Cancer accounts for ~60K new cases/year in the US alone; with a 5-year relative survival rate of 12%1
• · 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%2
• 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
• · CEACAM1 expression correlates with poor prognosis in Pancreatic cancer2
• Preclinical data support significant synergy of CM24 with currently marketed immuno-oncology therapies;
• Combining nivolumab with CM24 in a clinical collaboration with Bristol Myers Squibb; Purple Biotech retains all worldwide rights to CM24

1. https://seer.cancer.gov/statfacts/html/pancreas.htm L Interpex dence properces on more of estedes on the one in the lection mores to concert. (2020.02.2012) concept coment comer Them Clearces (202.02.12) concess (202.02.12 in doc.1177/7/278883309548
2. Nargilleri, Nikbere A, Sivel I, et al. NAPOL-1 phase 3 suby of lipotean in netastalic parcestic cancer. Firal overal survival and charceritics of l

Phase 2 Combination Study Design (NCT04731467)

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 :

OS

Secondary endpoints: OS rate @ 6 & 12 months, PFS, PFS rate @ 3 & 6 months, ORR

Additional Interim analysis: 2H24 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%).
• An analysis of the gemcitabine/nab-paclitaxel study will be performed when the data is sufficiently mature

PURPLE

Characteristic	Experimental (n=16)	Control (n=15)
Age (median)	દિ	68
Age ≥65 (n, %)	8 (50.0)	4 (26.7)
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% CI)	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

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

PURPLE

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 1H24
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
		16

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

Oncogene 2016; 35(20):2562-4; Flashner-Abramson,
rs. Clinical oncology 2018; 15(4): 234-248. Zi Ying et al. J Cell 334; Machado-Neto et al. Clinics 2018; 13, Maxu l buk, Mazyar Ghaffari, Halas Rever Ter. 2014; 13(12): 23(2): 330; 783p; Bampia e al. Mature rei

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

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

-30

-40

-50 -60

-70

-10 -6 24 12 24 50 100 24 12 100 12

-20 (b) (n) (n) (b) (b) (b) (n) (b) (b) (n) (n) (n) (n)

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

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

| 23

100

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

NK cells CD4 + /CD8 + T cells CD8 + NKG2A + T cells NK cell activation by inhibition of HLAE - NKG2A/CD94 binding CD4 + /CD8 + T cells activation through CD3 binding CD8 + NKG2A + T cells double activation through CD3 binding and NKG2A - HLA - E axis blocking Unleashing both innate and adaptive immune systems | 28

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 α.ΝKG2A arms in suppressing 5T4*NCSLC Patient-Derived Explant (PDE)* at 10nM concentration

* E wie oter teried in or en one of ested tom in mark ontected minne eller of mont mer der or mor her drency mor her der oper her der correst mand be site sterest of est man representing no viable cancer cells. The analysis included (celth) score of response (Response) using proprietary artificial intelligence (AJ) 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 1Q25

Purple Biotech (NASDAQ/TASE: PPBT)

As of March 31, 2024

• ADS Outstanding: 26.6 M .
• Cash Balance: \$10.8 M

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 ு இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இருக்கும் இ 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 Shively, 2013 Tsang, 2020 @ Immunology Cencer Biotherapya < 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"

URP

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%). . .

	Total	Grade
AE Term		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) 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.

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

Phase 1 study results (cont.): Identification of potential exploratory biomarkers supporting CM24's mechanism of action

Higher pre-treatment levels of tumor infiltrating lymphocytes that express CEACAM1 are associated with longer survival

• · consistent with the CM24 MoA in suppressing the immune evasion
• · suggest CEACAM1 expressing lymphocytes as a potential biomarker

CM24 treatment significantly reduced NET marker in serum

• · especially relevant in PDAC patients
• may be used as a pharmacodynamic marker

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 β-catenin activity and inhibit LS-513 cell viability. Combination of 5-FU and NT219 significantly inhibited the growth of CRC turnors in brain, using intracranial 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 synergy of NT2133. a MRTX1133-resistant. PDAC clone was developed. Inhibition of mKRAS G12Dsensitive (APC-1) and resistant (ASPC1-MRTX113-R) by NT219 (2D cell proliferation) shows 8-fold line (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 JRPLE 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