Purple Biotech Reports Positive Final Results from Randomized Phase 2 Study of CM24 in Second Line Pancreatic Cancer Final data demonstrate CM24 in combination with nivolumab and Nal-IRI/5FU/LV chemotherapy clear and con

Purple Biotech Reports Positive Final Results

from Randomized Phase 2 Study of CM24 in Second Line Pancreatic Cancer

REHOVOT, Israel, Dec. 02, 2024 (GLOBE NEWSWIRE) -- Purple Biotech

Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies

that overcome tumor immune evasion and drug resistance, today reported positive final results from the randomized Phase 2 study of its

lead oncology drug, CM24, a humanized monoclonal antibody that blocks CEACAM1, in patients with pancreatic ductal adenocarcinoma (PDAC).

"We are very excited about the final data,

demonstrating CM24's clear and consistent improvement across all efficacy endpoints evaluated in our randomized Phase 2 study,"

stated Purple Biotech CEO Gil Efron. "The enhanced results in patients with CEACAM1 and other serum markers gives us further optimism

that a biomarker enriched patient population selection could further strengthen CM24's magnitude of efficacy, potentially positioning

CM24 as a treatment for multiple CEACAM1-expressing malignancies in line with its mechanism of action."

Michael Cecchini, MD Associate Professor of Medicine

at the Yale Cancer Center, a principal investigator in this study, commented, "The promising results in PDAC, along with the identification

of a potential patient subgroup that may benefit from targeting CEACAM1 and NET serum levels, potentially position CM24 as an encouraging

treatment option. As a clinician, it is inspiring to see data that suggest the potential for improved outcomes in patients with late-stage

metastatic PDAC, who desperately need new and effective therapies. These findings support further investigation of CM24 in combination

with a checkpoint inhibitor and standard-of-care chemotherapy to improve outcomes not only in PDAC but also in other challenging cancer

Summary of Data and Findings:

The Phase 2 study evaluated CM24, a novel first-in-class

multi-functional anti-CEACAM1 antibody, in combination with Bristol Myers Squibb's immune checkpoint inhibitor nivolumab plus stand-of-care

(SoC) chemotherapy in second-line metastatic PDAC patients versus SoC chemotherapy alone. CM24 is a humanized monoclonal antibody that

blocks CEACAM1, a multi-faceted membrane glycoprotein that is one of the main proteins present on NETs, also acting as a pro-angiogenic

and anti-apoptotic agent collectively promoting tumor invasiveness, metastasis and immune evasion.

The primary endpoint of the study is OS and the

secondary endpoints include PFS, ORR and disease control rate (DCR). A Bayesian methodology was used to estimate the magnitude of effect

of the experimental arm versus the SoC arm in each chemotherapy cohort; the study was not powered for hypothesis testing. A total of 63

patients were enrolled, across 18 centers in the U.S., Spain, and Israel in 2 parallel and independent randomized study cohorts (total

of 2 arms per cohort). The experimental arms administered patients with CM24 plus nivolumab and a choice of one of two SoC chemotherapies

for second-line PDAC, dependent on prior first line therapy regimen; either gemcitabine/nab-paclitaxel or liposomal irinotecan (Nal-IRI)/5-fluorouracil

(5-FU) and leucovorin (LV) (Nal-IRI/5FU/LV), while the control arms administered either respective chemotherapy alone. CA19-9 as well

as additional exploratory biomarkers were also evaluated. Of the 63 patients enrolled, 32 were in the gemcitabine/nab-paclitaxel study

(experimental and control) and 31 were in the Nal-IRI/5FU/LV study (experimental and control). The gemcitabine/nab-paclitaxel-based part

of the study was impacted by informative censoring of the control arm that led to an imbalance between the control and experimental arms,

rendering this part of the study unsuitable for analysis; this part of the study has no impact on the CM24+nivolumab+Nal-IRI/5FU/LV portion

The study's final efficacy results in the

Nal-IRI/5FU/LV intent to treat (ITT) cohort population are summarized in the following table:

A consistent and continuous decrease of CA19-9, a clinically validated

PDAC biomarker, was observed in the experimental arm reaching a median percentage reduction from baseline of approximately 80% vs. an

increase of 40% in the control arm.

Subgroup analysis of patients with a range of pretreatment serum CEACAM1

between 6,000 pg/mL and 15,000 pg/mL, resulted in statistically significant results as follows:

An additional subgroup analysis of patients, which comprised 80% of

the patients in the study cohort, with a range of pretreatment serum CEACAM1 between 6,000 pg/mL and 15,000 pg/mL together with patients

with pretreatment serum Myeloperoxidase (MPO) levels of 200 ng/mL and 600 ng/mL, resulted in statistically significant results as follows:

Additional biomarkers analysis based on the patient

pretreatment biopsies, demonstrated significant OS and PFS benefit (HR 0.1, P=0.013 and HR 0.19, P=0.033, respectively) in patients with

both high tumor CEACAM1 ( 100) and low Combined Positive Score (CPS) ( 1) (a measure of PD-L1 positive tumor cells) supporting the

CM24/nivolumab combined treatment and its mechanistic rationale, and may open a new opportunity for patients who are not eligible for

anti-PD1 therapy in various indications

The CM24+nivolumab+Nal/IRI/5FU/LV regimen was

well tolerated, with the most frequent treatment emergent Grade 3 or higher adverse events being diarrhea (4 patients in the experimental

arm vs. 1 patient in the control arm), fatigue (2 patients in the experimental arm vs. no patients in the control) and neutropenia (2

patients in the experimental arm vs. no patients in the control). Accordingly, no meaningful difference in safety and tolerability were

observed between the experimental arm and SoC arm.

"The significant results in the subgroup

based on certain range of serum CEACAM1 and MPO levels, that covered 80% of the patients in the Nal-IRI cohort, is encouraging. We believe

that tumors with low CEACAM1 or NETs are less reliant on these targets whereas extremely high levels may suggest potential resistance

to the treatment. Based on the emerging role of neutrophil extracellular traps (NETs) in cancer and the positive findings of our study

in this selected population overlapping with CEACAM1 expression, we are planning a 3-arm Phase 2b study comparing either CM24 plus a PD1

inhibitor or CM24 monotherapy to SoC in multiple tumor types selected based on their NET and CEACAM1 expressions. This design will also

investigate the contribution of parts in regard to the need for PD1 blockade on top of CM24. We plan to target patients with higher serum

levels of CEACAM1 and MPO, as they are potentially more likely to benefit from CM24 treatment," stated Dr Michael Schickler, Head

of Clinical and Regulatory Affairs.

About Purple Biotech

Purple Biotech Ltd. (NASDAQ/TASE: PPBT) is a clinical-stage

company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance. The Company's oncology pipeline

includes CM24, NT219 and IM1240. CM24 is a humanized monoclonal antibody that blocks CEACAM1, that supports tumor immune evasion and survival

through multiple pathways. CEACAM1 on tumor cells, immune cells and neutrophils extracellular traps is a novel target for the treatment

of multiple cancer indications. As a proof of concept of these novel pathways, the Company is advancing CM24 as a combination therapy

with anti-PD-1 checkpoint inhibitors in a Phase 2 study for the treatment of pancreatic ductal adenocarcinoma (PDAC). The Company has

entered into a clinical collaboration agreement with Bristol Myers Squibb for the Phase 2 clinical trials to evaluate the combination

of CM24 with the PD-1 inhibitor nivolumab in addition to chemotherapy. NT219 is a dual inhibitor, novel small molecule that simultaneously

targets IRS1/2 and STAT3. A Phase 1 dose escalation study was concluded as a monotherapy and in combination with cetuximab in which NT219

demonstrated anti-tumor activity in combination with cetuximab in second line patients with recurrent and/or metastatic SCCHN (R/N SCCHN).

The Company is advancing CAPTN-3, a preclinical platform of conditionally-activated tri-specific antibody that engages both T cells and

NK cells to induce a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the

compound's therapeutic activity to the local tumor microenvironment, and thereby potentially increases the anticipated therapeutic window

in patients. The third arm specifically targets the Tumor Associated Antigen (TAA). The technology presents a novel mechanism of action

by unleashing both innate and adaptive immune systems to mount an optimal anti-tumoral immune response. IM1240 is the first tri-specific

antibody in development that targets 5T4 expressed in a variety of solid tumors and is correlated with advanced disease, increased invasiveness

and poor clinical outcomes. The Company's corporate headquarters are located in Rehovot, Israel. For more information, please visit https://purple-biotech.com/.

Forward-Looking Statements and Safe Harbor

Certain statements in this press release that

are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions

of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, statements that

are not statements of historical fact, and may be identified by words such as "believe", "expect", "intend",

"plan", "may", "should", "could", "might", "seek", "target", "will",

"project", "forecast", "continue" or "anticipate" or their negatives or variations of these words

or other comparable words or by the fact that these statements do not relate strictly to historical matters. You should not place undue

reliance on these forward-looking statements, which are not guarantees of future performance. Forward-looking statements reflect our current

views, expectations, beliefs or intentions with respect to future events, and are subject to a number of assumptions, involve known and

unknown risks, many of which are beyond our control, as well as uncertainties and other factors that may cause our actual results, performance

or achievements to be significantly different from any future results, performance or achievements expressed or implied by the forward-looking

statements. Important factors that could cause or contribute to such differences include, among others, risks relating to: the plans,

strategies and objectives of management for future operations; product development for NT219, CM24 and IM1240; the process by which such

early stage therapeutic candidates could potentially lead to an approved drug product is long and subject to highly significant risks,

particularly with respect to a joint development collaboration; the fact that drug development and commercialization involves a lengthy