On May 23, 2024 CureVac N.V. (Nasdaq: CVAC) ("CureVac"), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), reported financial results for the first quarter of 2024 and provided a business update (Press release, CureVac, MAY 23, 2024, View Source [SID1234643588]).

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"We have met an important first milestone in our ongoing organizational redesign by trimming our residual pandemic infrastructure. This achievement marks a crucial step in our journey towards greater efficiency and adaptability, ensuring we are well-positioned for the next phase of our corporate development. On the clinical development front, the pre-pandemic vaccine candidate against avian influenza, jointly developed with GSK, has received Fast Track designation from the U.S. FDA, which will support our efforts to provide pandemic preparedness and advance novel healthcare solutions," said Dr. Alexander Zehnder, Chief Executive Officer of CureVac. "Similarly, we have seen distinct signs of progress in our intellectual property litigation, with the quick resolution of co-ownership and co-inventorship claims made by Acuitas Therapeutics and expect our Pfizer/BioNTech U.S. case to reach court not long after its previously scheduled date of January 2025."

"We closed the first quarter of 2024 with €300.2 million in cash and cash equivalents. During this quarter, we fully settled the raw material commitments related to CVnCoV, our first-generation SARS-CoV-2 vaccine candidate," said Pierre Kemula, Chief Financial Officer of CureVac. "More than half of the cash spent in the first three months was related to such commitments. Looking forward, we consider this the end of a strong Q1 spend seasonality for CureVac. The second quarter will see the end of the remaining CVnCoV-related contract

termination provisions. Together with the ongoing organizational redesign, we anticipate a significantly lower cash burn in the future."

Selected Business Updates

Organizational Redesign

The organizational redesign, initiated in April 2024, is on track with the aim to streamline structures and reduce operating costs across most areas of the company. Rightsizing the company with a focus on trimming residual pandemic infrastructure is ongoing, with a planned reduction of 150 positions by year end. The organizational redesign is tailored to CureVac’s business scope and pipeline priorities, significantly increasing efficiency and performance while maintaining a strong focus on innovation and R&D activities.

The redesign will continue throughout 2024 through measures that are expected to result in financial savings from the second half of 2024 onwards and extend the company’s cash runway into the fourth quarter of 2025.

Prophylactic Vaccines

Executing on Broad Second-Generation mRNA Vaccine Program, Jointly Developed with GSK

CureVac continues to advance its clinical development programs in prophylactic vaccines in collaboration with GSK. All vaccine candidates currently in clinical development apply modified mRNA and are based on CureVac’s proprietary second-generation mRNA backbone, targeting improved intracellular mRNA translation for early and strong immune responses.

Avian Flu (H5N1) Program – U.S. FDA Fast Track Designation

In April 2024, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for a monovalent influenza A (H5N1) pre-pandemic vaccine candidate encoding an H5-antigen. The candidate is being developed in collaboration with GSK. The start of the Phase 1 part of a combined Phase 1/2 study was announced on April 24, 2024, assessing the safety, reactogenicity and immunogenicity of the vaccine candidate in healthy younger and older adults.

The FDA Fast Track designation enables facilitated development and accelerated review of drug candidates addressing serious conditions and fulfilling an unmet medical need. The H5N1 avian influenza virus is known to sporadically cross species from its original bird host to other animals and humans and is considered a potential future pandemic threat. Based on CureVac’s proprietary second-generation mRNA backbone, the vaccine candidate aims to contribute to pandemic preparedness against avian influenza and provide an effective countermeasure in the event of human-to-human transmission of the H5N1 virus.

Protection of Intellectual Property Rights

CureVac is asserting its intellectual property rights in litigation against Pfizer/BioNTech in Germany, the U.S. and the UK.

On April 25, 2024, a settlement with Acuitas Therapeutics was reached, resolving co-ownership and co-inventorship claims regarding one patent family covering four patents that are at issue in the U.S. litigation against Pfizer/BioNTech. Under the terms of the settlement, Acuitas acknowledges CureVac’s ownership of certain patent claims and has agreed to dismiss its co-ownership and co-inventorship claims. In return, CureVac acknowledges that Acuitas holds licenses to selected patents, including three out of four disputed U.S. patents. These three patents will be withdrawn from the U.S. patent litigation against Pfizer/BioNTech.

Accordingly, the U.S. litigation against Pfizer/BioNTech will proceed under the original four patent families, now covering seven U.S. patents. A trial is expected to begin in the second quarter of 2025, with the date to be announced within the next few weeks.

In Germany, the settlement and out-licensing of selected patents to Acuitas Therapeutics will lead to the withdrawal of two utility models from the Pfizer/BioNTech litigation, covering equivalent claims to the three patents withdrawn in the United States. Accordingly, litigation in Germany will proceed with a total of six IP rights.

The German litigation recently progressed after CureVac filed an appeal with the Supreme Court of Justice, opposing the first-instance decision by the German Federal Patent Court on December 19, 2023 to nullify the German part of CureVac patent EP 1 857 122 B1. A trial date is expected in the second half of 2025.

Financial Update for the First Quarter of 2024

Cash Position

Cash and cash equivalents amounted to €300.2 million at the end of March 2024, decreasing from €402.5 million at the end of 2023. In the first three months of 2024, cash used in operations was mainly allocated to the last payments related to the termination of raw material commitments for the first-generation vaccine, amounting to a total of €52 million. Looking forward there will be no further raw material payments related to CVnCoV. The remaining cash spend was mainly related to ongoing R&D activities.

In the second quarter of 2024, the company expects to fully settle all remaining CMO-related provisions stemming from CVnCoV. The company reaffirms its cash runway into the fourth quarter of 2025.

Revenues

Revenues amounted to €12.4 million for the first quarter of 2024, representing an increase of €5.3 million, or 74%, from €7.1 million for the same period in 2023.

The year-on-year increase was primarily driven by higher revenues from the GSK and CRISPR collaborations. For the three months ending March 31, 2024, total revenues of €8.9 million and €3.5 million were recognized, respectively, compared to €6.5 million and €0.2 million in the prior year period.

Operating Result

Operating loss amounted to €73.3 million for the first quarter of 2024, representing an increase of €12.9 million from €60.4 million for the same period in 2023.

The operating result was affected by several key drivers mainly related to the closing of the first-generation vaccine effort in COVID-19:

· Cost of sales increased primarily due to an increase of contract termination provisions as part of an arbitration ruling for Contract Manufacturing Organization activities related to the first-generation COVID-19 vaccine.

· Research and development expenses increased primarily with increased activity in oncology R&D projects and development of the R&D workforce. Additionally, the first quarter of 2024 was impacted by increased expenses related to the litigation to enforce intellectual property rights.

· General and administrative expenses decreased compared to the prior year period due to lower workforce in the corporate service functions and in the Management Board.

· Other income increased year-on-year due to the sale of raw materials to GSK.

Financial Result (Finance Income and Expenses)

Net financial result for the first quarter of 2024 amounted to €3.4 million, or an increase of €0.4 million, from €3.0 million for the same period in 2023. This increase was mainly driven by interest income on cash investments.

Pre-Tax Loss

Pre-tax loss was €69.9 million for the first quarter of 2024, compared to €57.4 million in the same period of 2023.

On May 8, 2024 Cullinan Therapeutics, Inc. (Nasdaq: CGEM), a biopharmaceutical company focused on developing modality-agnostic targeted therapies, reported first clinical data from its Phase 1 dose escalation cohort of CLN-619 in combination with checkpoint inhibitor (CPI) pembrolizumab and updated results from the monotherapy dose escalation cohort in patients with advanced solid tumors (Press release, Cullinan Oncology, MAY 23, 2024, View Source [SID1234643587]). Findings from the clinical trial will be shared at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting as a poster presentation during the "Developmental Therapeutics—Immunotherapy" session (Abstract #2588, Poster Bd 67) on June 1, 2024, 9:00 AM-12:00 PM Central Time.

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Summary of Key Clinical Results from Combination Arm of Phase 1 Clinical Trial in Patients with Solid Tumors:

•
Of 22 patients treated with CLN-619 in combination with pembrolizumab, 18 were RECIST-evaluable for response.
•
Confirmed partial responses (PR) were observed in 3 patients treated with CLN-619 at doses ≥3mg/kg in combination with pembrolizumab.
•
Responses were observed in patients with tumor types not typically responsive to CPI treatment.

Characteristics of Responders

Tumor Type

Number of Prior Lines of Therapy

Prior CPI

CPI Responsive Tumor (Yes/No?)

Best Response

Duration of Response (Weeks)

NSCLC, EGFR exon 18/21

6

No

No

PR

24

NSCLC, ALKr

2

No

No

PR

12.7

Gastric, HER2+

3

No

Yes

PR

8.9+ (ongoing)

Summary of Efficacy in NSCLC (monotherapy and combination cohorts)

•
Objective responses and stable disease (SD) were observed in patients with NSCLC with oncogenic mutations in the CLN-619 monotherapy and combination cohorts.
o
8 of the 11 patients with NSCLC were RECIST-evaluable; of these, 6 had oncogenic mutations.
o
3 of the 6 patients with oncogenic mutations experienced clinical benefit – there were 2 PRs and 1 SD lasting >18 weeks.
Summary of Updated Key Clinical Results from Monotherapy Arm of Phase 1 Clinical Trial in Patients with Solid Tumors:

•
Among 42 patients treated with CLN-619 monotherapy, 29 received CLN-619 at a dose ≥1 mg/kg and were RECIST-evaluable.
•
The clinical benefit rate (CBR) was 41.4% (1 complete response (CR), 2 PR, 9 SD ≥18 weeks).

Characteristics of Patients with Response or SD ≥18 weeks

Tumor Type

Number of Prior Lines of Therapy

Best Response

Duration of Response (Weeks)

Responders (n=3)

Mucoepidermoid parotid

2

CR

71

Endometrial (serous, MMRp)

5

PR

31

Endometrial (endometrioid, MMRp)

3

PR

55+ (ongoing)

SD ≥18 weeks (n=9)

Cervical squamous (n=2); breast (ER/PR+, HER2−; n=1); ovarian (n=1); endometrial carcinosarcoma (n=1); mediastinal intimal sarcoma (n=1); adenoid cystic carcinoma (n=1); pancreatic adenocarcinoma (KRAS G12V; n=1); NSCLC (STK11m; n=1)

Mean: 3.6

Range: 1–7

SD ≥18 wks

Range: 18–56

Summary of Safety Data

CLN-619 was well tolerated in combination with pembrolizumab and as monotherapy. Most treatment-related adverse events (TRAEs) were grade 1/2.

TRAEs reported in ≥10% of safety-evaluable patients (combination: n=22; monotherapy: n=42) were infusion-related reactions (IRRs) (combination: 18.2%; monotherapy: 28.6%) and fatigue (combination: 18.2%; monotherapy: 9.5%). The only grade ≥3 TRAE reported in >5% of patients in any group was increased AST (combination: 0; monotherapy: 7.1%). One patient in each cohort discontinued study treatment due to TRAEs (4.5% combination and 2.4% monotherapy). There were no treatment-related deaths.

IRR was the most frequently reported TRAE with CLN-619. With administration of prophylactic pre-medications, most IRRs were grade 1 or 2, occurred on Day 1 of Cycle 1, and resolved quickly.

"Our initial clinical findings show that the combination of CLN-619, a novel antibody targeting MICA/B, with pembrolizumab may benefit patients whose cancer is not typically amenable to checkpoint inhibitor therapy. More specifically, we observed objective responses in patients with ALK- and EGFR-mutated NSCLC who had relapsed after tyrosine kinase inhibitors (TKIs), patients who do not typically respond to checkpoint inhibitors," said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. "Additionally, longer-term follow-up for patients treated with CLN-619 monotherapy shows favorable safety and durable clinical benefit with extended treatment, including objective responses and prolonged stable disease in multiple tumor types and in patients with disease progression after CPI therapy. We are encouraged by these data and have initiated monotherapy and combination expansion cohorts in NSCLC."

"There remains significant unmet need for patients with NSCLC with oncogenic mutations relapsing after TKIs, so we see a potential benefit in novel therapies that can be easily combined with established CPIs," said Alexander Spira, MD, PhD, FACP, FASCO, Director, Virginia Cancer Specialists Research Institute and Director, NEXT Oncology Virginia. "Combining CLN-619 with pembrolizumab engages multiple immune effector cells, including innate cells by CLN-619 and T cells by pembrolizumab. The safety profile of CLN-619 along with the biologic rationale for combination with CPI make this a potentially synergistic approach."

CLN-619 Further Development Plan

CLN-619 is being studied in an ongoing Phase 1 clinical trial (NCT05117476) both as monotherapy and in combination with pembrolizumab. The study design allows dose level extensions as well as expansion in tumor-specific cohorts. Consistent with prespecified criteria and based on initial safety and efficacy observations, Cullinan has initiated monotherapy and combination expansion cohorts in NSCLC. Enrollment continues in previously declared expansion cohorts in cervical (monotherapy) and endometrial cancers (monotherapy and combination). CLN-619 will also be studied in a Phase 1 clinical trial (NCT06381141) in patients with relapsed/refractory multiple myeloma.

Virtual and Live Investor Event

Cullinan Therapeutics will host an Investor Event on Saturday, June 1, 2024, at 6:30 PM Central Time, during which Dr. Jeff Jones, Chief Medical Officer at Cullinan Therapeutics, will present the CLN-619 data shared at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and Dr. Alexander Spira, Director, Virginia Cancer Specialists Research Institute and Director, NEXT Oncology Virginia, will share an overview of the current treatment landscape for EGFR-mutated NSCLC. Investors and analysts are invited to register to attend in-person by emailing Chad Messer, VP Investor Relations ([email protected]). A live webcast will be available via the events page of the Company’s investor relations website at View Source and a replay will be available shortly after the conclusion of the live event.

About CLN-619

CLN-619 is a potential first-in-class humanized IgG1 monoclonal antibody that binds to the stress induced ligands MICA and MICB, which are expressed on a wide variety of solid tumors and hematologic malignancies. Engagement of MICA/B by the activating receptor NKG2D, present on both cytotoxic innate and adaptive immune cells, results in target cell lysis. However, tumor cells can shed MICA/B via proteases they release into the tumor microenvironment, resulting in evasion of immune-mediated destruction. CLN-619 functions by restoring MICA/B expression on the surface of tumor cells to reinvigorate NKG2D-mediated immune activation, and by inducing antibody-dependent cellular toxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), together promoting anti-tumor activity via multiple immune-mediated mechanisms. CLN-619 is being studied in an ongoing Phase 1 clinical trial (NCT05117476) both as a monotherapy and in combination with pembrolizumab. The study design allows dose level extensions as well as expansion in tumor-specific cohorts. CLN-619 will also be studied in a Phase 1 clinical trial (NCT06381141) in patients with relapsed/refractory multiple myeloma.

On May 23, 2024 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS) reported that senior management will present at the upcoming TD Cowen 5th Annual Oncology Innovation Virtual Summit: Insights for ASCO (Free ASCO Whitepaper) & EHA (Free EHA Whitepaper) on Wednesday, May 29, 2024 at 12:00 p.m. Eastern Daylight Time / 9:00 a.m. Pacific Daylight Time (Press release, Coherus Biosciences, MAY 23, 2024, View Source [SID1234643585]). The presentation will be accessible via Webcast through a link on the Investor Events and Presentations section of the Coherus website: View Source This webcast will be available for replay until June 26, 2024.

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On May 23, 2024 CatalYm reported that positive new follow-up results from its ongoing "GDFATHER" Phase 1/2a trial (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 1/2a) will be featured in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024 in Chicago (Press release, Catalym, MAY 23, 2024, View Source [SID1234643584]).

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The trial is evaluating CatalYm’s lead GDF-15 neutralizing antibody, visugromab, in combination with immune checkpoint inhibitor nivolumab in late- to last-line, anti-PD-1/PD-L1 relapsed/refractory patients. Visugromab is designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15), a central mediator of immune resistance to cancer therapies. Early interim data of the study, which were previously presented at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2023, demonstrated signs for potent and durable anti-tumor efficacy as well as an excellent tolerability and safety profile for visugromab in combination with nivolumab in advanced-stage/last-line non-small cell lung cancer (NSCLC) and urothelial cancer patients (UC). Now matured data for NSCLC, UC and novel data for hepatocellular cancer (HCC) will be presented.

The ASCO (Free ASCO Whitepaper) Annual Meeting will be held in Chicago, Illinois, from May 31 to June 4, 2024.

Oral Presentation Details:
Presentation Title: Effects of neutralization of tumor-derived immunosuppressant GDF-15 on anti-PD-1 activity in anti-PD-(L)1 relapsed/refractory non-squamous NSCLC, urothelial, and hepatocellular cancer
Presenter: Dr. Ignacio Melero Bermejo, MD | Clinica Universidad de Navarra
Session: Developmental Therapeutics-Immunotherapy
Session Date and Time: Sunday, June 2, 2024, from 11:30 AM – 1:00 PM CDT
Location: S406 | On Demand | McCormick Place
Abstract Number: 2513

The full abstract details can be accessed via View Source The company will provide further information and a summary of the data following the oral presentation at ASCO (Free ASCO Whitepaper).

On May 23, 2024 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported topline overall survival data from its phase 2 clinical trial of CAN-2409, a multimodal biological immunotherapy candidate, plus valacyclovir (prodrug), together with standard of care (SoC) immune checkpoint inhibitor (ICI) therapy in patients with Stage III/IV non-small cell lung cancer (NSCLC) inadequately responding to ICI (anti-PD-(L)1) therapy (Press release, Candel Therapeutics, MAY 23, 2024, View Source [SID1234643583]). The data will be presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held in Chicago, May 31 to June 4, 2024, by Charu Aggarwal, MD, MPH, FASCO, Leslye M. Heisler Associate Professor for Lung Cancer Excellence at the Perelman School of Medicine, University of Pennsylvania and Co-Principal Investigator of the clinical trial.

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Highlights of the presentation include: 1) median overall survival (mOS) of 20.6 months achieved in patients with progressive disease despite ICI treatment after two administrations of CAN-2409 plus prodrug; for context, in a 2022 publication of a clinical trial in a similar patient population, mOS in the control arm that received SoC docetaxel-based chemotherapy was 11.6 months; improved survival was observed across both PD-(L)1 positive and PD-(L)1 negative tumors; 2) beneficial effect on both

injected and uninjected tumors in more than 70% of the patients with metastatic disease and at least one uninjected tumor; and 3) a significant increase in circulating CD8+ cytotoxic and CD4+ effector and central memory T cells and increased soluble granzyme B levels in peripheral blood after the second (‘booster’) injection of CAN-2409, associated with subsequent prolonged survival (in each case, as of an April 1 data cut-off). Together, these data continue to support the emerging differentiated profile of CAN-2409 in this difficult-to-treat condition.

"The results from our phase 2 trial in NSCLC continue to support the tremendous promise of CAN-2409 across multiple solid tumors. We are particularly encouraged by the overall survival observed in the patients whose disease had progressed despite receiving prior anti-PD-(L)1 treatment. Improved overall survival is, ultimately, what matters to patients and to the regulators," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "These results, together with our recently reported overall survival data in a randomized clinical trial in pancreatic cancer, add to the growing body of evidence supporting the notion that CAN-2409 treatment may convert progressive cancer into stable disease associated with survival benefit in advanced cancers with high unmet medical needs."

Previously, the Company received FDA Fast Track Designation for CAN-2409 in NSCLC and pancreatic cancer as well as orphan drug designation in pancreatic cancer.

"Current therapeutic options for advanced NSCLC patients whose disease progresses despite ICI treatment are limited; they are characterized by poor tolerability and limited clinical benefit," said Charu Aggarwal, MD, MPH, FASCO. "The data reported today suggest that CAN-2409 can reactivate these patients’ exhausted immune systems, including those with low PD-(L)1 expression. This systemic anti-tumor immune response translated to a durable response; increased numbers of circulating cytotoxic and memory T cells were associated with subsequent prolonged survival. I look forward to the continued development of CAN-2409 in NSCLC as a promising approach in an area of unmet therapeutic need."

ASCO presentation highlights:

•
The open label phase 2 clinical trial evaluated the efficacy and safety of the combination of CAN-2409 plus prodrug (valacyclovir) and continued, unaltered ICI therapy in patients with an inadequate response to ICI after at least 18 weeks of treatment. The objective of the analysis presented at ASCO (Free ASCO Whitepaper) was to explore whether experimental treatment with CAN-2409 plus prodrug could improve mOS in patients treated with two injections.
•
46 patients received two administrations of CAN-2409 plus prodrug and were evaluable per protocol.

Cohort 1

Stable Disease at Study Entry

n=5

Cohort 2

Progressive Disease at Study Entry

n=41

•
Demographic characteristics of the safety population:
img160460863_1.jpg

•
We confirmed previously released data on the ability of CAN-2409 to control disease, with a disease control rate of 100% in cohort 1 and 70% in cohort 2 patients.
•
As of April 1, 2024, mOS of 22.0 months was observed across all 46 patients who had an inadequate response to ICI (both cohorts 1 and 2).
In patients with progressive disease despite ICI treatment (cohort 2), a mOS of 20.6 months was observed. A 2022 publication of a clinical trial in a similar patient population reported mOS of 11.6 months for SoC docetaxel-based chemotherapy.1

•
Improved mOS was observed in both PD-(L)1 negative and PD-(L)1 positive tumors in patients with progressive disease (n=37 patients in cohort 2 for which PD-(L)1 status at baseline was available).
PD-(L)1 Subgroup

Number of Patients

mOS (months)

Negative (<1%)

16

24.5 (7.0, NA)

Positive (>=1%)

21

20.6 (5.5, NA)

•
71.4% of patients with metastatic disease and at least one uninjected tumor (n=35) experienced a beneficial effect on both injected and uninjected tumors, indicating a systemic anti-tumor immune response. When using a threshold of >5% decrease, more than 60.0% of patients showed an abscopal response.

•
Increased numbers of circulating CD8+ cytotoxic and CD4+ effector and central memory T cells as well as elevated levels of soluble granzymes B and H after the second CAN-2409 injection were associated with subsequent prolonged survival, underpinning the systemic immune response elicited by CAN-2409 treatment.

•
Treatment with CAN-2409 in NSCLC continued to exhibit a favorable safety and tolerability profile. Bronchoscopic delivery of CAN-2409 is an extension of
existing care for patients with NSCLC. As of April 1, 2024, there were no dose-limiting toxicities or grade 4 or higher treatment-related adverse events (TRAEs); the majority of TRAEs were grade 1 or 2, and there were three grade 3 TRAEs (one pyrexia, two pneumonitis).

Details on the CAN-2409 ASCO (Free ASCO Whitepaper) abstract are as follows:

•
Poster Presentation Title: Overall survival after treatment with CAN-2409 plus valacyclovir in combination with continued ICI in patients with stage III/IV NSCLC with inadequate response to ICI

•
Presenter: Charu Aggarwal, MD, MPH, FASCO, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Perelman School of Medicine, University of Pennsylvania

•
Session Title: Poster Session – Lung Cancer – Non-Small Cell Metastatic

•
Session Date/Time: Monday, June 3, 2024; 1:30 PM – 4:30 PM CT

•
Location: Hall A, McCormick Place Convention Center, Chicago, IL

About CAN-2409

CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the tumor. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events.

Currently, Candel is evaluating CAN-2409 in NSCLC, borderline resectable PDAC, and localized, non-metastatic prostate cancer in ongoing clinical trials. CAN-2409 plus prodrug (valacyclovir) has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy, and localized primary prostate cancer. Candel’s pivotal phase 3 clinical trial in prostate cancer is being conducted under a Special Protocol Assessment with the FDA. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC.