On February 14, 2023 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that it submitted a new drug application (NDA) resubmission to the US Food and Drug Administration (FDA) for the HEPZATO Kit (melphalan hydrochloride for Injection/Hepatic Delivery System or Melphalan/HDS) seeking approval for the treatment of patients with unresectable hepatic-dominant metastatic ocular melanoma (mOM) (Press release, Delcath Systems, FEB 14, 2023, View Source [SID1234627198]).

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The resubmission is in response to a September 12, 2013 Complete Response Letter (CRL) from the FDA. The NDA resubmission contains comprehensive data and information to address all issues identified in the CRL. The FDA is expected to determine whether the resubmission constitutes a complete response and is eligible for review within 30 days. Once accepted for review by the FDA, a new PDUFA action date will be established for the HEPZATO Kit application.

"The submission is a critical milestone for Delcath and represents the culmination of years of work by investigators and employees," said Gerard Michel, CEO of Delcath. "We look forward to receiving feedback from the FDA regarding a PDUFA date within 30 days."

On February 14, 2023 Cullinan Oncology, Inc. (Nasdaq: CGEM) and Harbour BioMed (HKEX: 02142) reported that Cullinan Oncology has entered into an exclusive license with Harbour BioMed for the development and commercial rights of HBM7008 (CLN-418) in the U.S. CLN-418/HBM7008 is a B7H4 x 4-1BB bispecific immune activator developed from next-gen heavy chain only antibody (HCAb)-based multi-specific antibody discovery platform HBICE, currently in a Phase 1 clinical study being conducted at U.S. and Australian sites in patients with advanced solid tumors (Press release, Cullinan Oncology, FEB 14, 2023, View Source [SID1234627196]).

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"We are pleased to bring CLN-418, a potential first-in-class, clinical-stage bispecific immune activator, into our diversified portfolio. We believe the best approach to conditional activation of 4-1BB is by targeting B7H4, a tumor associated antigen that is highly expressed across multiple cancers and minimally overlaps with PD-L1 expression. CLN-418 is a strong strategic fit for Cullinan, building on our expertise with bispecifics, and placing us at the forefront of bispecific antibody development in solid tumors. Importantly, this transaction adds another clinical-stage asset to our portfolio, and with it, we are on track to have potentially six clinical stage assets in our pipeline by the end of 2023," said Nadim Ahmed, Chief Executive Officer of Cullinan Oncology. "This transaction is consistent with our goal to strategically deploy capital to expand and advance our pipeline, and the financial terms of the agreement allow us to maintain a multi-year cash runway to fund our ongoing development efforts and deliver data from multiple clinical programs. Harbour BioMed is a global clinical-stage biotech company with experienced therapeutic innovation capabilities and a network of partnerships, and we look forward to realizing the full potential of this exciting program."

Under the agreement, Cullinan Oncology will pay Harbour BioMed an upfront license fee of $25 million at closing for the exclusive right to develop and commercialize CLN-418/HBM7008 in the U.S. Harbour BioMed will be eligible to receive up to $148M in development and regulatory milestones plus up to an additional $415M in sales-based milestones as well as tiered royalties up to high teens on potential U.S. commercial sales.

"This agreement is another validation from a leading global biotech company on our technology platforms and innovation capabilities. We believe that Cullinan Oncology is the ideal partner to continue the development of CLN-418/HBM7008, which we believe has first-in-class potential to treat a wide range of solid-tumor cancers. They have a seasoned clinical development team, strong capabilities in oncology drug development, and the robust infrastructure necessary to move it forward," said Dr. Jingsong Wang, Founder, Chairman and CEO of Harbour BioMed. "We look forward to working with Nadim and his team to advance this program forward."

Cullinan Oncology Conference Call Information

Cullinan Oncology will host a conference call on Tuesday, February 14 at 8 a.m. ET. Investors and the general public are invited to listen to a live webcast of the call. A link to join the call and to find related materials will be available at: investors.cullinanoncology.com/events

About CLN-418/HBM7008

CLN-418/HBM7008 is the only B7H4 x 4-1BB bispecific immune activator in clinical studies. Both B7H4 and 4-1BB have been targets of high interest and both have been evaluated clinically. Their distinct biology and mechanisms of action provide strong rationale to combine them as a bispecific antibody.

B7H4 is an attractive tumor associated antigen (TAA) highly expressed on multiple tumor types, including triple negative breast cancer, ovarian cancer, and lung cancer, while expression on normal tissue is low. A coinhibitory immune checkpoint with PD-L1 in the B7 family, B7H4 has minimal overlap with PD-L1 expression. Targeting B7H4 has the potential to address tumor types for which PD-L1-based immunotherapies have exhibited limited efficacy.

4-1BB is a key costimulatory molecule for both T- and NK-cell engagement and is being studied in multiple clinical programs. However, safety concerns such as hepatic toxicity remain despite the biological validation of the 4-1BB pathway. Conditional activation of 4-1BB in the tumor microenvironment that is dependent on B7H4 expression presents a novel approach to harness the potential of both targets. CLN-418/HBM7008, with strict TAA crosslinking dependent T-cell activation, can potentially translate to better safety and a more favorable therapeutic window.

The ongoing Phase 1 trial (NCT05306444) is an open-label, multicenter study being conducted at U.S. and Australian sites evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of CLN-418/HBM7008 administered intravenously in patients with advanced solid tumors. The study, which is expected to enroll up to 108 subjects, aims to identify a maximum tolerated dose and a recommended Phase 2 dose of CLN-418/HBM7008. Initial clinical data from this study could be available in 2024.

On February 14, 2023 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that rilvegostomig, AstraZeneca’s bi-specific antibody derived from Compugen’s COM902, is expected to progress into Phase 3 this year (Press release, Compugen, FEB 14, 2023, View Source [SID1234627195]). AstraZeneca announced plans to initiate a Phase 3 trial for rilvegostomig (previously AZD2936), a PD-1/TIGIT bi-specific antibody and is also developing an expanded Phase 2 program.

"We are excited that AstraZeneca, a global leader in the development of oncology therapeutics, plans to advance its PD-1/TIGIT bi-specific derived from our COM902 into a Phase 3 trial this year. In addition, we are happy to see that AstraZeneca continues to swiftly grow the rilvegostomig Phase 2 program across multiple indications including non-small cell lung cancer and gastric cancer," said Anat Cohen-Dayag, Ph.D., President, and Chief Executive Officer of Compugen. "We believe that the continued expansion of the rilvegostomig clinical program demonstrates the commitment to explore the potential of TIGIT and our differentiated anti-TIGIT, COM902. Like COM902, a reduced Fc effector function anti-TIGIT antibody, rilvegostomig was engineered to reduce Fc effector functionality, with the potential to enhance anti-tumor activity. We have always believed that this could be the optimal design for an anti-TIGIT and we look forward to seeing how it plays out in the clinic. While TIGIT blocking antibodies may function in PD-L1 high expressing patients, our data consistently show that addition of an anti-PVRIG may sensitize tumors to also respond to PD-1 and TIGIT blockade even in PD-L1 low expressing patients. As leaders in the DNAM-1 axis space, we believe that evaluating the triple combination of COM902, with COM701, our anti-PVRIG, and pembrolizumab has the potential to maximize clinical benefit for patients."

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Dr. Cohen-Dayag added, "Our license agreement with AstraZeneca is part of our strategy to broaden opportunities for our pipeline, taking advantage of bi-specifics for combination development while maintaining our focus on the development of COM902 as part of various combinations either by Compugen or in collaboration with future partners, including in combination with COM701, our potential first-in-class anti-PVRIG antibody."

About the Compugen-AstraZeneca License Agreement
In 2018, Compugen and AstraZeneca entered into an agreement, as amended, by which Compugen provided an exclusive license to AstraZeneca to use Compugen’s monospecific antibodies that bind to TIGIT, including COM902, for the development of bi-specific and multi-specific antibody products, excluding such bi-specific and multi-specific antibodies that also bind to PVRIG, PVRL2 and/or TIGIT. AstraZeneca is responsible for all research, development, and commercial activities. AstraZeneca has the right to create multiple products under this license. To date, Compugen has received a $10 million upfront payment, an additional $15.5 million in milestone payments and is entitled to receive up to an aggregate $200 million in development, regulatory and commercial milestones for the first product, as well as tiered royalties on future product sales. If additional bi or multi-specific products are developed based on Compugen’s monospecific antibodies that bind to TIGIT, additional milestones and royalties would be due to Compugen.

On February 14, 2023 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported that Purinergic Signalling, a peer-reviewed scientific journal focused on molecules which target adenosine receptors, published an article titled "Targeting the A3 adenosine receptor to treat hepatocellular carcinoma: anti-cancer and hepatoprotective effects" authored by Can-Fite’s CEO Dr. Pnina Fishman and others (Press release, Can-Fite BioPharma, FEB 14, 2023, View Source [SID1234627191]).

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The article includes a review of the novel approach for treating advanced liver cancer with Namodenoson, a small molecule orally bioavailable drug which specifically kills cancer cells and leaves normal liver cells unharmed. Efficacy and safety data are presented from Phase I and II human clinical studies. Treatment with Namodenoson resulted in longer overall survival in patients with advanced liver cancer as defined by Child Pugh B (CPB) stage in a statistically significant manner. The drug has shown to have a very favorable safety profile and exert a protective effect on liver cancer cells.

Currently, Namodenoson is being evaluated in a pivotal Phase III study. The study protocol has been approved by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) with 450 patients to be enrolled in Israel, Europe, and the U.S. An interim data analysis will be performed.

Namodenoson has been granted both Orphan Drug and Fast Track designations by the FDA and has received Orphan Drug status with the EMA.

"With Namodenoson, we are aiming to treat patients with the greatest need—those with advanced liver cancer CPB. Moreover, this category of patients are typically not enrolled by other clinical studies due to the severity of their disease," Dr. Fishman stated. "We are hopeful that Namodenoson’s novel approach may be effective in our current pivotal Phase III trial based on positive results in our prior Phase II study with this advanced liver cancer population. Additionally, we are highly encouraged by the case of a patient from the Phase II study who cleared all liver cancer and remains cancer-free for six years while treated with Namodenoson."

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On February 14, 2023 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class, effective and durable therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported that the first patient has been dosed in the randomized part of the open label Phase 2 clinical trial evaluating CM24 in the treatment of advanced metastatic pancreatic cancer (PDAC) (Press release, Purple Biotech, FEB 14, 2023, View Source;id=254755&p=2258208&I=1206939-c7Z3G6f3m8 [SID1234627190]).

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The ongoing Phase 2 trial is investigating CM24, a novel, first-in-class monoclonal antibody that targets CEACAM1, which promotes tumor immune evasion. The study design compares, in a randomized fashion, treatment with CM24 combined with the PD-1 immune checkpoint inhibitor nivolumab and standard of care (SoC) chemotherapy vs. SoC chemotherapy in second line PDAC patients. Purple Biotech has now treated the first patient in this randomized Phase 2 study that is designed to include approximately 30 patients in the experimental cohort and approximately additional 30 patients in the control cohort. The Company has already enrolled 10 patients in the safety run-in part of the trial during which no dose-limiting toxicities (DLTs) have been observed to date. The study is currently being conducted in 11 sites in the United States, Spain and Israel, and Purple Biotech expects to open approximately 10 additional sites in the upcoming months. The primary endpoint of this randomized part of the trial is overall survival. The Company expects to share interim results in the second half of 2023 and a topline report on the overall study by the end of 2024.

"We are excited with the progress made in this study as we start its randomized part," said Gil Efron, Chief Executive Officer of Purple Biotech. "Patients with metastatic pancreatic cancer such as those we are enrolling in our ongoing trial have very few therapeutic options, with relatively short duration of survival. If this study is successful, it may open a path for a short time to market."