Calidi Biotherapeutics, a clinical-stage biotechnology company, is leading the charge in developing a new generation of targeted antitumor virotherapies. With a focus on harnessing the power of oncolytic viruses and stem cell-based delivery systems, Calidi is poised to redefine the landscape of cancer treatment.
Company Background and Focus
Founded in 2016, Calidi has quickly established itself as a trailblazer in the field of immuno-oncology. The company's comprehensive pipeline includes several promising product candidates, each designed to address the unique challenges posed by different cancer types. Calidi's initial focus was on developing innovative stem cell-based and enveloped platforms for the delivery and potentiation of oncolytic virotherapies to treat cancer. These product candidates were designed to protect oncolytic viruses from being quickly inactivated by the patient's immune system and target tumor sites.
Product Pipeline
CLD-101 NeuroNova Platform
One of Calidi's flagship programs is CLD-101, also known as the NeuroNova Platform, which targets high-grade glioma (HGG), an aggressive and often fatal form of brain cancer. The CLD-101 candidate utilizes an engineered oncolytic adenovirus delivered by neural stem cells, with the goal of enhancing tumor targeting and viral amplification. In June 2021, Calidi entered into a License Agreement with Northwestern University to obtain the exclusive commercialization rights to this investigational new drug and data generated from Northwestern's phase 1 clinical trial treating brain tumor patients. In a completed phase 1 clinical trial at Northwestern University, CLD-101 demonstrated a favorable safety profile in patients with newly diagnosed HGG. Calidi is now preparing to commence a phase 1b clinical trial to further explore the dosing regimen and evaluate biomarkers.
Prior to Calidi's licensing agreement with Northwestern University, an open-label, investigator-sponsored, Phase 1 clinical trial for NNV1 in patients with newly diagnosed high-grade gliomas was completed. This clinical trial demonstrated that single administration of CLD-101.00 was well tolerated in patients with newly diagnosed HGG. Subject to funding, Northwestern University anticipates commencing a Phase 1b clinical trial during the first quarter of 2025. This trial will explore the final dosing regimen for NNV1, including the feasibility of repeated dosing in newly diagnosed HGG. Extensive biomarker analysis will be performed on tumor biopsies and blood samples to determine viral distribution, specific tumor targeting and induction of anti-tumor immunity.
CLD-101 for Recurrent HGG (NNV2)
Complementing the CLD-101 program, Calidi is also developing CLD-101 for the treatment of recurrent HGG, known as CLD-101 for Recurrent HGG or NNV2. In July 2021, Calidi entered into an Exclusive License Agreement with City of Hope and the University of Chicago for patents covering cancer therapies using an oncolytic adenovirus loaded into allogeneic neural stem cells for treatment of high-grade glioma. This program is currently in a phase 1 study evaluating the safety and feasibility of repeated doses of CLD-101 administered intracerebrally to patients with recurrent high-grade gliomas.
A phase 1 study evaluating the safety and feasibility of administering repeated doses of CLD-101.00 intracerebrally to patients with recurrent high-grade gliomas began treatment in May 2023. The study is being run by Calidi's partner, City of Hope, and started enrolling cohort 4 in January 2024. Clinical data from patients with recurrent HGG treated with repeated doses of CLD-101.00 is planned to support the start of a trial of repeated doses in newly diagnosed HGG.
CLD-201 SuperNova Program
Another key focus area for Calidi is the CLD-201 SuperNova program, an internally developed pre-clinical candidate targeting advanced solid tumors, including triple-negative breast cancer, head and neck squamous cell carcinoma, and advanced soft tissue sarcoma. The SuperNova Delivery Platform utilizes allogeneic adipose-derived mesenchymal stem cells loaded with a tumor-selective oncolytic vaccinia virus, with the goal of enhancing tumor targeting and viral amplification. Calidi anticipates commencing a phase 1 clinical trial for CLD-201 in the first half of 2025.
Based on its pre-clinical studies, Calidi believes SNV1 has therapeutic potential for the treatment of multiple solid tumors such as head and neck cancer, triple-negative breast cancer and melanoma. Calidi has held a pre-IND meeting with FDA to discuss the filing of its IND application for the clinical development of CLD-201.00.
Adult Allogeneic Adipose-derived (AAA) Stem Cells Research
Expanding beyond oncology, Calidi is also engaged in early discovery research involving Adult Allogeneic Adipose-derived (AAA) stem cells for various indications and therapies. These multipotent stem cells have the potential to differentiate into various cell lineages, offering possibilities for regenerative applications, such as in cosmetics, orthopedics, and autoimmune diseases.
CLD-301.00 AAA for Multiple Indications is an early discovery research program involving Adult Allogeneic Adipose-derived (AAA) stem cells for various indications and therapies. These AAA stem cells are theoretically multipotent, differentiating along the adipocyte, chondrocyte, myocyte, neuronal, and osteoblast lineages, and may have the ability to serve in other capacities, such as providing hematopoietic support and gene transfer with potential applications for repair and regeneration of acute and chronically damaged tissues. Pre-clinical studies involving toxicity and efficacy will be needed before an IND application may be filed with the FDA.
CLD-400 RTNova Program
Calidi's innovative approach to cancer treatment is further exemplified by its CLD-400 RTNova program, which is in the exploratory stages of development. RTNova is a systemic antitumor virotherapy composed of an engineered vaccinia virus enveloped by a cell membrane, designed to target lung cancer and advanced metastatic disease. The unique enveloped technology aims to enhance the virus's ability to survive in the bloodstream and target multiple distant tumor sites.
CLD-400.00 RTNova for Lung Cancer and Metastatic Solid Tumors is Calidi's pre-clinical program involving enveloped oncolytic viruses, which builds upon its experience of using cells to protect, potentiate and deliver virotherapies. The CLD-400.00 program is derived from research from Calidi's prior pre-clinical CLD-202.00 program. RTNova consists of an engineered vaccinia virus enveloped by a cell membrane, that is potentially capable of targeting lung cancer and advanced metastatic disease due to its increased ability to survive in the bloodstream. In preclinical studies, RTNova has shown early signs of its resistance to human humoral immunity and capability to target multiple distant and diverse tumors and transform their microenvironments leading to their elimination. In addition, the program has shown potential synergistic effects with other immunotherapies, including cell therapies, to attack and eliminate disseminated solid tumors.
Strategic Partnerships and Licensing
Calidi's commitment to advancing its pipeline is evidenced by its strategic partnerships and licensing agreements. In 2021, the company obtained the exclusive commercialization rights to the CLD-101 NeuroNova Platform from Northwestern University, and in the same year, it licensed the CLD-101 for Recurrent HGG program from City of Hope.
Financials and Liquidity
Financially, Calidi has relied on a combination of private placements, convertible notes, and public offerings to fund its operations. As of September 30, 2024, the company reported a cash balance of $1.9 million and restricted cash of $0.2 million. However, Calidi has acknowledged that its existing cash resources may not be sufficient to support its operations for the next 12 months, and the company will need to raise additional capital to continue its development efforts.
Despite the challenges, Calidi remains focused on executing its strategic plan. In October 2024, the company announced the closing of a $2 million registered direct offering and concurrent private placement, which will provide additional funding to advance its pipeline.
For the three months ended September 30, 2024, Calidi reported no revenue and a net loss of $5.1 million. The company's net loss for the nine months ended September 30, 2024, was $18.1 million. As of September 30, 2024, Calidi had an accumulated deficit of $117.6 million.
The company's financial position is characterized by a debt-to-equity ratio of -0.877, a current ratio of 0.19, and a quick ratio of 0.19. These metrics indicate that Calidi faces significant financial challenges and will need to secure additional funding to support its ongoing operations and research initiatives.
Calidi operates primarily in the United States and has not yet reported any revenue from its product candidates, which are still in various stages of development and clinical trials.
Scientific Presentations and Recognition
Furthermore, Calidi has been actively presenting data supporting its innovative platforms at renowned scientific conferences, such as the International Oncolytic Virotherapy Conference (IOVC) and the Society for Immunotherapy of Cancer (SITC) Annual Meeting. These presentations have garnered attention and validation for Calidi's unique approaches to targeting and treating various cancer types.
Future Outlook
Looking ahead, Calidi Biotherapeutics is poised to continue its momentum as it navigates the complex landscape of cancer research and drug development. With a robust pipeline, strategic partnerships, and a commitment to innovation, the company aims to make a lasting impact on the lives of cancer patients worldwide.
The company expects to continue incurring significant and increasing expenses and operating losses for the foreseeable future as it advances its current and future product candidates through preclinical and clinical development, manufactures drug product and drug supply, seeks regulatory approval for its current and future product candidates, maintains and expands its intellectual property portfolio, hires additional research and development and business personnel, and operates as a public company.
Company History and Public Listing
During Calidi's time as a private company, it faced various challenges in securing financing to advance its preclinical and clinical pipeline. The company relied heavily on investments from its CEO and largest shareholder, as well as other related parties, to fund its operations. In September 2023, Calidi consummated a business combination with First Light Acquisition Group, Inc., a special purpose acquisition company. As a result of the transaction, Calidi became a publicly-traded company listed on the NYSE American exchange under the ticker symbol CLDI. The combined company was renamed Calidi Biotherapeutics, Inc. The transition to becoming a public company through the business combination provided Calidi with additional capital to continue developing its novel cell-based and enveloped oncolytic virotherapy platforms.
Subsidiary and Technology Services
Calidi's subsidiary, Nova Cell, Inc., was formed to be a technology service provider that develops innovative stem cell-based products using Calidi's cellular manufacturing process. Through Nova Cell, Calidi anticipates expanding potential uses from oncology to other fields that require regenerative medical applications, such as cosmetics, orthopedics, auto-immune diseases, and various other therapies.