On October 18, 2023 Exelixis, Inc. (Nasdaq: EXEL) reported that its third quarter 2023 financial results will be released on Wednesday, November 1, 2023 after the markets close (Press release, Exelixis, OCT 18, 2023, View Source [SID1234636105]). At 5:00 p.m. ET / 2:00 p.m. PT, Exelixis management will host a conference call and webcast to discuss the results and provide a general business update. Access to the event is available via the Internet from the company’s website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To access the conference call, please register using this link. Upon registration, a dial-in number and unique PIN will be provided to join the call. To access the live webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. Please connect to the company’s website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. A webcast replay of the conference call will also be archived on www.exelixis.com for one year.

On October 18, 2023 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported that the Company presented data characterizing the preclinical profile of its EpCAM-targeting ADC, CX-2051, at the World ADC conference taking place October 16-19, 2023, in San Diego, CA (Press release, CytomX Therapeutics, OCT 18, 2023, View Source [SID1234636104]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"CX-2051 is designed to address the unmet needs of patients with EpCAM-expressing tumors, including colorectal cancer, where EpCAM expression is uniformly high. EpCAM is a broadly expressed, validated anti-cancer target that to date has been limited in its development potential due to systemic, on-target off-tumor dose-limiting toxicities", said Marcia P. Belvin, Ph.D., senior vice president and chief scientific officer at CytomX.

Continued Dr. Belvin, "Based on our experience with the Probody Platform and our clinical experience with Probody-ADCs, we have designed CX-2051 to mask target binding in normal tissues and include a next-generation topoisomerase-1 inhibitor payload. We are encouraged by the compelling preclinical profile of CX-2051 and anticipate filing an IND for the program by the end of the year. We aim to launch Phase 1 dose escalation for CX-2051 in solid tumors in 2024, with an initial focus in metastatic colorectal cancer as a priority indication."

Details for the presentation are as follows:
Presentation Title: Leveraging Conditional Activation to Localize Antibody Drug Conjugates to the Tumor
"Clinical Lessons" Track
Session Date and Time: October 18, 2023, 12:30 pm PST

The full presentation is available at the following link:

Leveraging Conditional Activation to Localize Antibody Drug Conjugates to the Tumor
Marcia P. Belvin, Ph.D., Senior Vice President, Chief Scientific Officer, CytomX Therapeutics

On October 18, 2023 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported the publication of results from the multicenter, multiregional, pivotal trial evaluating cosibelimab, a differentiated and potential best-in-class anti-PD-L1 antibody, in patients with metastatic cutaneous squamous cell carcinoma ("cSCC"), in the Journal for ImmunoTherapy of Cancer (JITC), the peer-reviewed, online journal of the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Checkpoint Therapeutics, OCT 18, 2023, View Source [SID1234636103]). The paper, entitled, "Efficacy and Safety of Cosibelimab, an Anti–PD-L1 Antibody, in Metastatic Cutaneous Squamous Cell Carcinoma" (doi:10.1136/jitc-2023-007637), describes safety and efficacy results from 78 patients with metastatic cSCC enrolled at clinical sites in eight countries.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Patients received cosibelimab 800 mg every two weeks as an intravenous infusion until disease progression or unacceptable toxicity. The study’s primary endpoint was objective response rate ("ORR") assessed by independent central review using Response Evaluation Criteria in Solid Tumors, v.1.1. As of the pre-specified data cutoff date, the primary endpoint was met with highly clinically meaningful results. Median duration of response was not yet reached. The authors observed that cosibelimab treatment was associated with lower rates of severe immune-related adverse events ("irAEs") as compared with those reported for similar studies of PD-1-targeting agents, concluding that cosibelimab may address an area of unmet clinical need for effective and better tolerated treatments for patients with metastatic cSCC who are ineligible for curative surgery or radiation.

"The conclusions of the study are clear," commented Prof. Philip Clingan of Southern Medical Day Care Centre in Wollongong, Australia, Principal Investigator for this study and first author of the paper. "Cosibelimab is the first PD-L1-blocking antibody to demonstrate a robust and clinically meaningful ORR, with durable responses in participants, and a well-tolerated safety profile in patients with metastatic cSCC. While existing PD-1-blocking antibodies are approved to treat advanced cSCC, many patients don’t respond to treatment, experience severe irAEs or are simply not appropriate candidates for PD-1 therapy treatment, such as those that are immunocompromised, immunosuppressed or with preexisting autoimmune disease. There is therefore a significant need for improved therapies. Cosibelimab, if approved, would offer patients an important new treatment option through its dual activation of both innate and adaptive immunity to induce strong and durable anti-tumor responses, complemented by lower rates of severe adverse events as cosibelimab’s binding to PD-L1 leaves the interaction of PD-1 and PD-L2 unaltered."

"Publication of these data expands the growing evidence supporting the efficacy and safety of cosibelimab," said James Oliviero, President and Chief Executive Officer of Checkpoint. "We are encouraged by recently revealed longer-term data from our pivotal studies of cosibelimab, which demonstrate a deepening of response over time. We believe cosibelimab’s dual mechanism of action and potential favorable safety profile should position the product as the preferred immunotherapy of oncologists for the large number of high-risk cSCC patients upon its potential launch early next year. We continue to work with the U.S. Food and Drug Administration ("FDA") toward the January 3, 2024, action date for our Biologics License Application for cosibelimab."

About Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1 million cases according to the Skin Cancer Foundation. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced, and an estimated 15,000 people will die from their disease each year. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear.

About Cosibelimab
Cosibelimab is a potential best-in-class, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 ("PD-L1") and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity ("ADCC") for potential enhanced efficacy in certain tumor types.

On October 18, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported that it received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for CB-012, an allogeneic anti-C-type lectin-like molecule-1 (anti-CLL-1) CAR-T cell therapy (Press release, Caribou Biosciences, OCT 18, 2023, View Source [SID1234636102]). CB-012 will be evaluated in the multicenter, open-label, AMpLify Phase 1 clinical trial for patients with relapsed or refractory acute myeloid leukemia (r/r AML).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Clearance of our IND application for CB-012 represents another significant milestone for Caribou as our third off-the-shelf CAR-T cell therapy enters the clinic," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "We look forward to initiating patient enrollment in the AMpLify Phase 1 trial by the middle of 2024 to evaluate the safety and tolerability of CB-012 in patients suffering from AML."

CLL-1 is a compelling therapeutic target because it is highly expressed on AML cells and leukemic stem cells, but it is not expressed on hematopoietic stem cells.

"There is an urgent need to develop new treatments for patients with relapsed or refractory AML, for which the treatment options are predominantly limited to salvage chemotherapy regimens," said Naval Daver, MD, associate professor and director, Department of Leukemia, The University of Texas MD Anderson Cancer Center. "An allogeneic CAR-T cell therapy that could safely and effectively target AML blasts while preserving healthy hematopoietic stem cells could provide a much-needed off-the-shelf option for these patients."

Caribou’s patented next-generation CRISPR Cas12a chRDNA genome-editing technology platform maintains high genomic integrity and significantly improves the specificity of genome editing.

"CB-012 was engineered with five genome edits, and is the first allogeneic CAR-T cell therapy, to our knowledge, with both checkpoint disruption through a PD-1 knockout, and immune cloaking through a B2M knockout and B2M–HLA-E fusion transgene insertion," said Steve Kanner, PhD, Caribou’s chief scientific officer. "Both armoring strategies are designed to improve the antitumor activity of CB-012 that we believe are crucial for targeting this difficult to treat indication."

About the AMpLify trial
The AMpLify Phase 1 trial is an open-label, multicenter clinical trial designed to evaluate CB-012 in adult patients with relapsed or refractory acute myeloid leukemia (r/r AML). Part A, a 3+3 dose escalation design, will evaluate the safety and tolerability of CB-012 at ascending dose levels to determine the maximum tolerated dose and/or the recommended doses for expansion. Part B is the dose expansion portion with the primary objective of determining antitumor response, assessed by overall response rate (ORR), after a single dose of CB-012. AMpLify will include patients who have not responded to or relapsed after standard treatment and will exclude patients who have been treated with more than 3 prior lines of therapy and patients with proliferative disease. Caribou plans to initiate patient enrollment in the AMpLify trial to treat patients with a single administration of CB-012 at dose level 1 (25×106 CAR-T cells) by mid-2024.

About acute myeloid leukemia
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and is the most common type of acute leukemia in adults. It is estimated there will be 20,380 new cases of AML in the United States in 2023. The five-year survival rate for these patients is approximately 30%. AML is currently treated with chemotherapy, targeted therapies, and/or allogeneic or autologous stem cell transplant. For patients with relapsed or refractory AML, there are few treatment options and median overall survival is typically less than seven months.

On October 18, 2023 Candel Therapeutics, Inc. (the Company or Candel) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing viral immunotherapies to help patients fight cancer, reported that Nature published results from the ongoing first-in-human phase 1 investigator-sponsored clinical trial of CAN-3110, a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate, in patients with recurrent high-grade glioma (HGG), of which 86.7% were glioblastoma, that had returned after standard of care (SoC) treatment (Press release, Candel Therapeutics, OCT 18, 2023, View Source [SID1234636101]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study is being conducted in a collaboration between Brigham and Women’s Hospital and Candel. The publication titled "Clinical trial links oncolytic immunoactivation to survival in glioblastoma" can be accessed at View Source

Key findings of the manuscript: Tolerability of a single injection of CAN-3110 in recurrent HGG with no dose limiting toxicity reported, improved median overall survival in 41 patients treated in Arm A (11.6 months as of data cutoff in October 2022) and correlation between anti-HSV-1 serology and survival. Importantly, CAN-3110 treatment was associated with a significant increase in immune cells in the tumor

microenvironment and in the peripheral blood. The activation of both local and systemic immune response, including the expansion of the T-cell repertoire diversity as well as HSV-1 immune status, correlate with survival suggesting that CAN-3110 can enhance anti-cancer immune responses even in immunosuppressive tumor microenvironments.

"There is an urgent need to develop novel therapies for recurrent HGG," said E. Antonio Chiocca, MD, PhD, Head of Department of Neurosurgery at Brigham and Women’s Hospital, Professor at Harvard Medical School, and Principal Investigator of the clinical trial. "Failure of standard of care and conventional immunotherapy in recurrent HGG largely resides in the inability of available therapies to efficiently activate the immune system in the cold tumor microenvironment that is characteristic for this condition. In this manuscript we provide evidence that, after a single injection, the direct oncolytic activity combined with the ability of CAN-3110 to elicit a strong anti-tumoral response, resulted in conversion of the cold tumor microenvironment and induced a systemic immune response linked to improved patient survival."

Dr. Chiocca continued, "Prolonged survival was associated with HSV-1 seropositivity, either before or after CAN-3110 treatment. Importantly, approximately 30% of seronegative patients at baseline seroconverted after CAN-3110 treatment. Those patients also exhibited increased survival suggesting the possibility of leveraging this mechanism and further improving survival upon multiple injections."

"This high impact publication detailing results from 41 patients in the phase 1 clinical trial of CAN-3110 is an important validation of how Candel, in collaboration with academic leaders in the field, are working to address the critical challenges in recurrent HGG," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "In the clinical study, we observed a nearly doubling of the expected median overall survival after a single CAN-3110 injection, compared to historical reports of less than 6 to 9 months. We reported transformative improvements after a single injection of CAN-3110 in patients affected by aggressive tumors who had failed multiple resections, chemotherapy and radiotherapy."

Dr. Tak continued, "As a next step, we are currently evaluating the effects of multiple CAN-3110 injections in recurrent HGG, supported by the Break Through Cancer foundation. The data reported in the manuscript reinforce our confidence in CAN-3110 and its potential to change disease outcomes in difficult-to-treat solid tumors that express Nestin. In the future, we could possibly expand the development of this agent into other indications characterized by Nestin expression, such as triple negative breast cancer or sarcoma."

"The publication of this manuscript in Nature, strongly underscores the relevance and novelty of our clinical and biological findings," said Francesca Barone, MD, PhD, Chief Scientific Officer of Candel. "The molecular construct of CAN-3110 makes this virus unique as a next generation viral immunotherapy candidate, combining in a single agent potent oncolysis and immune activation. Of importance, patients with recurrent HGG who had pre-existing antibodies to HSV-1 virus (66% of the patients) had a median overall survival of 14.2 months. In these patients, we observed clear evidence of immune activation in the tumor microenvironment. Those without antibodies (34%) had median overall survival of 7.8 months, which is in the same range as historical survival

times. Different from conventional immunotherapy, CAN-3110 is designed to expand but also diversify the immune response. Accordingly, we observed increased diversity of the T-cell receptor repertoire after a single injection of CAN-3110 in recurrent HGG patients. We have started to evaluate the effects of repeated injection with CAN-3110, which has the potential to result in the HSV-1 seroconversion associated with improved survival."

About the phase 1 clinical trial of CAN-3110 in recurrent HGG

This investigator-sponsored study is led by E. Antonio Chiocca, MD, PhD, Head of the Department of Neurosurgery at Brigham & Women’s Hospital and Professor at Harvard Medical School. The clinical trial comprises three arms. In arm A, 41 patients with recurrent HGG were treated by a single intratumoral injection of CAN-3110 (dose ranging from 1×106 plaque forming units (pfu) to 1×1010 pfu), including nine patients with multifocal/multicentric, deep or bilateral tumors associated with poor survival. After observing this regimen was generally well tolerated without dose-limiting toxicity, patients in arm B (n=9) were treated with a single dose of cyclophosphamide (24 mg/kg), two days before CAN-3110 injection at doses of 1 x 108 pfu (n=3) and 1 x 109 pfu (n=6). The rationale is based on findings in mouse models, where cyclophosphamide improved viral persistence in injected tumors. In arm C, supported by the Break Through Cancer foundation, two cohorts of 12 patients with recurrent HGG will receive up to six injections of CAN-3110 over a four-month period.

Early results from the phase 1 clinical trial were presented in May 2023 at the American Society of Gene and Cell Therapy 26th Annual Meeting. The oral presentation highlighted that in arm A (n=41), treatment with a single dose of CAN-3110 was generally well tolerated and resulted in median overall survival (mOS) of 11.8 months as of the data cutoff date on April 20, 2023. In addition, at the same data cutoff date, median overall survival in arm B (n=9) was ongoing at 12.0 months, supporting the encouraging clinical activity of CAN-3110 observed in in arm A. Of note, responses were shown in both injected and uninjected lesions in patients with multifocal disease. Analysis of post treatment samples demonstrated evidence of persistent HSV antigen expression and replication in uninjected tumor tissue associated with CD8+ T cell infiltration, which may explain the clinical responses observed in uninjected tumors.