On September 13, 2023 Titan Pharmaceuticals, Inc. ("Titan" or the "Company") reported to have entered into a Securities Purchase Agreement (the "Purchase Agreement") with The Sire Group Ltd. ("Sire Group" or the "Investor"), pursuant to which the Company has agreed to issue 950,000 shares of Series AA Convertible Preferred Stock, par value $0.001 per share (the "Series AA Preferred Stock") to the Investor at a price of $10.00 per share, for an aggregate purchase price of $9,500,000 (the "Private Placement"). The purchase price consists of (i) $5 million in cash at closing and (ii) $4.5 million in the form of a promissory note from Sire Group, personally guaranteed by a principal of Sire Group, due and payable on September 23, 2023, subject to two 10-day extensions which include additional payments of $50,000 for each extension. The terms, rights, obligations and preferences of the Series AA Preferred Stock are set forth in a Certificate of Designations, Preferences and Rights of Series AA Convertible Preferred Stock of the Company (the "Certificate of Designations"), filed with the Secretary of State of the State of Delaware on September 13, 2023. Copies of the form of Purchase Agreement and the Certificate of Designations are attached hereto as Exhibits 10.1 and 4.1, respectively, and are incorporated herein by reference.

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Under the Certificate of Designations, each share of Series AA Preferred Stock will be convertible, at the holder’s option at any time, into shares of the Company’s common stock at a conversion rate equal to the quotient of (i) the stated value of such share divided by (ii) the initial conversion price of $0.466, subject to specified adjustments as set forth in the Certificate of Designations. Based on the initial conversion rate, approximately 20,386,266 shares of the Company’s common stock would be issuable upon conversion of all the shares of Series AA Preferred Stock, when issued, assuming the absence of in-kind dividends. The Series AA Preferred Stock will contain limitations that prevent the Investor from acquiring the lower of either (i) the maximum percentage of common stock permissible under the rules and regulations of The Nasdaq Stock Market ("Nasdaq") without first obtaining shareholder approval or (ii) 19.99% of the Company’s outstanding common stock.

The holder of the Series AA Preferred Stock is entitled to receive dividends on shares of the Series AA Preferred Stock equal (on an as-if-converted-to-common-stock basis) to and in the same form as dividends actually paid on shares of the common stock. No other dividends will be paid on shares of the Series AA Preferred Stock. Any shares of Series AA Preferred Stock may, at the option of the holder, be converted at any time into that number of shares of common stock at the conversion price set forth above. The Series AA Preferred Stock does not have any voting rights. In the event of any liquidation, dissolution or winding up of the Company, the holder of the Series AA Preferred Stock will be entitled to receive out of the assets, whether capital or surplus, of the Company the same amount that a holder of common stock would receive if the Series AA Preferred Stock were fully converted to common stock, which amounts shall be paid pari passu with all holders of common stock. The foregoing description provides a summary of certain material terms of the Series AA Preferred Stock issued pursuant to the Purchase Agreement, as set forth in Certificate of Designations, which is filed as Exhibit 4.1 to this Current Report on Form 8-K and is incorporated herein by reference.

The shares sold in the Private Placement do not involve a public offering and have not been registered under the Securities Act of 1933, as amended, in reliance on Regulation S thereunder.

Registration Rights Agreement

In connection with the Private Placement, the Company entered into a registration rights agreement with the Investor (the "Registration Rights Agreement") pursuant to which the Company has agreed to provide certain registration rights upon the occurrence of certain events set forth in the Registration Rights Agreement. The foregoing description of the Registration Rights Agreement does not purport to be complete and is qualified in its entirety by the full text of the Registration Rights Agreement, which is filed as Exhibit 10.2 to this Current Report on Form 8-K and is incorporated herein by reference.

On September 13, 2023 Bioneer reported that The Innovation Fund has invested approximately DKK 12.3 million in a research project aimed at developing a biological drug candidate that represents a completely new concept in cancer treatment (Press release, Bioneer, SEP 13, 2023, View Source;utm_medium=rss&utm_campaign=the-innovation-fund-invests-in-the-development-of-cym-001-an-innovative-bispecific-antibody-to-treat-metastatic-castration-resistant-prostate-cancer-bampc [SID1234635201]). The molecule, CYM-001, owned by Cymab ApS, is a bispecific antibody that stimulates the body’s own immune system to fight cancer cells.

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In the past decade, immune therapy biologics, known as checkpoint inhibitors, have revolutionized cancer treatment. They are becoming more widely used, with an estimated global market of $22 billion in 2023. However, with the expansion of checkpoint inhibitors, it has become clear that there are limitations, and there are large patient groups who cannot benefit from the treatment as their tumors are non-immunogenic, as is the case with certain types of advanced-stage prostate cancer.

Non-immunogenic tumors in mCRPC are the initial target for CYM-001. Each year, about 1300 men in Denmark die from prostate cancer, with a mortality rate that has remained largely unchanged for decades (Association of The Nordic Cancer Registries). Both in Denmark and the USA, prostate cancer is the second most common cancer-related cause of death in men, surpassed only by lung cancer. Existing treatment options for late stages of prostate cancer are currently limited and are not curative for several patient subgroups, including mCRPC. Existing treatment options also often have severe side effects. Impotence and incontinence are frequent consequences, resulting in reduced quality of life for patients.

The goal of the project is initially to develop a treatment for non-immunogenic tumors within metastatic prostate cancer, but it is expected to be applicable to several cancer types. The project is based on experiences with approved drugs combined with new scientific discoveries. Laboratory testing of various molecular prototypes has been ongoing for the past two years.

The project will aim to achieve crucial preclinical and CMC development, as well as clarify the clinical development for CYM-001 into a product for the treatment of metastatic prostate cancer. CYM-001 has the potential to be the first product of a new class of biological drugs that increase the quantity and effectiveness of immune cells in the tumor and are thus effective for cancer treatment where existing immune therapy falls short.

The project is a collaboration between the University of Southern Denmark, Research Unit for Clinical Physiology and Nuclear Medicine, Bioneer A/S, and Cymab ApS. At the University of Southern Denmark, Mikael Palner, Head of the Preclinical Imaging Core Facility and Associate Professor, and Christina Baun, Radiographer, will be responsible for translational pharmacological studies to characterize CYM-001. At Bioneer A/S, Christian Clausen, CSO, and Alexandra Baer, R&D Manager Upstream Development Mammalian Cells, will be responsible for cell line and Master Cell Bank development of CYM-001. Together, the partners have extensive experience in drug development, from molecular design and preclinical testing to the development of production methods that enable clinical testing.

Johan Faber, CEO, Cymab ApS. "By both stimulating the body’s own immune cells and directing them directly towards the tumor, the treatment is expected to be effective against cancer types that are not responsive to existing immune therapy. This provides doctors with an entirely new tool in the fight against so-called non-immunogenic or ‘cold’ tumors, unlike today, where there are essentially no effective treatments. The original field of potential drug candidates has now been narrowed down to one, and the new investment from the Innovation Fund enables the crucial development towards the ultimate goal of bringing new treatment options to an area of cancer treatment where nothing currently exists. It’s fantastic."

Hans Wandall, Prof. MD and Chairman, Cymab ApS. "The lack of recruitment of the body’s immune cells in non-immunogenic tumors is observed in several other cancer types besides prostate cancer. By targeting the binding of the molecule to these cancer types, the concept has broad potential as a new treatment paradigm."

Stine Kjellev, CSO, Cymab ApS. "We will be able to offer a better and more targeted treatment with fewer side effects for the types of cancer where the body’s own immune cells do not effectively collaborate with the existing treatment. Our therapy, which we call Targeted Immune Stimulation, abbreviated as TIMS, has the potential to ensure that the same revolutionary effect delivered by checkpoint inhibitors can now also be offered to patient groups with non-immunogenic tumors."

Mikael Palner, Head of the Preclinical Imaging Core Facility and Associate Professor, University of Southern Denmark. "At the Research Unit for Clinical Physiology and Nuclear Medicine, we are at the forefront of diagnostics and are developing groundbreaking methods to improve patients’ quality of life. Therefore, it is truly exciting to be part of this project, which has the potential to revolutionize current treatment options and make a huge difference for the affected patients."

Christian Clausen, CSO, Bioneer A/S. "Bioneer develops cell lines that can be used for the production of new biological drugs. We are working on new methods to improve cell lines to produce more efficiently, as well as to produce more complex proteins. We look forward to collaborating on this new type of prostate cancer treatment project."

On September 13, 2023, SQZ Biotechnologies Company (the "Company" or "SQZ"), F. Hoffmann-La Roche Ltd ("Roche Basel") and Hoffmann-La Roche Inc. ("Roche US", and together with Roche Basel, "Roche") agreed to terminate the License and Collaboration Agreement, dated October 5, 2018, by and between the Company and Roche (as amended or modified, the "Agreement"), effective September 13, 2023 (the "Effective Date") (Filing, 8-K, SQZ Biotech, SEP 13, 2023, View Source [SID1234635185]). No early termination penalty will be incurred by either party. On the Effective Date, the Company will regain full clinical development and future commercialization rights for all its oncology programs, including human papilloma virus ("HPV") 16 positive tumors.

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Under the terms of the Agreement, the Company and Roche had agreed to jointly develop certain products based on mononuclear antigen presenting cells ("APCs"), including HPV, using the SQZ APC platform for the treatment of oncology indications. The Company granted Roche a non-exclusive license to its intellectual property, and Roche granted the Company a non-exclusive license to its and its affiliates’ intellectual property for the purpose of performing research activities. Under the Agreement, Roche was granted option rights to obtain an exclusive license to develop APC products or products derived from the collaboration programs on a product-by-product basis and to develop a Tumor Cell Lysate ("TCL") product. For each of the APC products and TCL product, if Roche exercised its option and paid a specified incremental amount, Roche would have received worldwide, exclusive commercialization rights for the licensed products.

The foregoing is only a summary of the material terms of the Agreement, does not purport to be complete and is qualified in its entirety by reference to the full text of (i) the License and Collaboration Agreement, dated October 5, 2018, by and between the Company and Roche, which was filed as Exhibit 10.7 to the Company’s Registration Statement on Form S-1, filed with the Securities and Exchange Commission (the "Commission") on October 9, 2020, and (ii) the Accord relating to License and Collaboration Agreement, dated November 5, 2019, between the Company and Roche, which was filed as Exhibit 10.8 to the Company’s Registration Statement on Form S-1, filed with the Commission on October 9, 2020.

On September 13, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that the median Overall Survival (mOS) and Overall Response Rate (ORR) for patients receiving NOX-A12 with the VEGF inhibitor bevacizumab and radiotherapy has now exceeded what TME Pharma believes to be all relevant competitor therapy trials in newly diagnosed glioblastoma patients resistant to standard chemotherapy (Press release, TME Pharma, SEP 13, 2023, View Source [SID1234635156]).

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After 17 months on study (median1), 67% of GLORIA expansion arm patients (4 of 6) are still alive. The median Overall Survival is expected to improve further as the remaining patients continue to receive treatment or follow-up care2.

The milestone in survival at 17 months is a crucial landmark since it means the NOX-A12-based therapy has surpassed the survival rates achieved in what TME Pharma believes to be all the relevant competitor studies conducted in the US or EU involving newly diagnosed, chemotherapy-resistant (MGMT unmethylated) glioblastoma patients (see annex to this press release). In addition, the NOX‑A12-based therapy achieved this result despite having a more difficult population to treat since only patients with residual detectable tumor after surgery were included the NOX-A12 trial, while competing trials included patients with complete removal of detectable tumor.

OS: 17 months (and increasing) for NOX-A12 + bevacizumab vs 13.4-16.9 months
With Overall Survival (OS) of 67% at 17 months demonstrated by NOX-A12 combined with radiotherapy and bevacizumab, the median Overall Survival (mOS) will continue to improve since more than 50% of patients are still alive. This compares favorably to the 13.4 to 16.5 months mOS in the chemotherapy resistant population demonstrated by relevant competing therapies in clinical development and to the 16.9 months demonstrated by the Tumor Treating Fields device that was approved by the US Food and Drug Administration (FDA) for newly-diagnosed glioblastoma in 2015.

ORR: 83% for NOX-A12 + bevacizumab vs 3-7.8%
NOX-A12 combined with radiotherapy and bevacizumab demonstrated a strong Overall Response Rate (ORR) of 83%, which compares favorably with much lower percentages of 3%, 7% and 7.8% demonstrated by paxalisib, enzastaurin and nivolumab, respectively.

"This positive clinical update marks a significant step forward in our mission to transform the landscape of cancer treatment. The 17-month data and the exceptional survival rates in the GLORIA trial underscore the potential for NOX-A12 regimens to become the best available therapy for glioblastoma patients. We will need to confirm this potential in a larger, randomized trial," said Aram Mangasarian, CEO of TME Pharma. "We are immensely proud of the dedicated team of researchers and clinicians who have contributed to this remarkable achievement; they will provide detailed clinical updates at the upcoming Society for Neuro-Oncology (SNO) conference in November. We believe that continued strong performance of NOX-A12 clearly supports further development of the NOX-A12 + anti-VEGF combination with radiotherapy and improves NOX-A12’s profile for partnering and eligibility for accelerated regulatory pathways."

Annex: Competing benchmark therapies against chemotherapy resistant glioblastoma in development in the US or EU

Experimental Agent
(Company)

Surgical removal of
detectable tumor
(T=total; P=partial;
B=biopsy only)

Patient
number

Response
criteria

Overall
Response
Rate (ORR)

Median Overall
Survival (mOS)
in months

Status

Reference

NOX-A12 + Radiotherapy + bevacizumab (TME Pharma)

0% T; 100% P

6

RANO

83%

>17
(67% OS at 17m)

Ph 1/2 ongoing

TME Pharma Internal Data

Tumor Treating Fields (TTF) + Radiotherapy + Temozolomide (Novocure)

53% T; 34% P; 13% B

209

Macdonald

n.a.

16.9

Approved

Stupp R (2017), JAMA

Val-083 after Radiotherapy + Temozolomide chemotherapy) (Kintara)

information not provided

36

RANO

n.a.

16.5

Fast Track Designation granted; Ph 2/3 GBM AGILE ongoing

O’Brien (2021), Society for Neuro-Oncology Annual Meeting

Paxalisib + Radiotherapy (Kazia)

77% T; 17% P; 10% B

30

RANO

3%

15.7

Failed pre-defined criteria for GBM AGILE trial Ph 3

Wen P (2022); J Clin Oncol.

Enzastaurin + Radiotherapy (Denova)

43.9% T; 40.4% P; 15.8 B

57

Macdonald

7%

15

Fast Track Designation granted; Ph 3 ongoing

Wick W (2013), Neuro Oncol.

Temozolomide chemotherapy + Radiotherapy + bevacizumab (Roche)

63% T; 34% P; 3% B #

215

Macdonald

n.a.

14.3

Failed in Ph 3

Gilbert MR (2014), NEJM

Nivolumab anti-PD-1 immunotherapy + Radiotherapy (BMS)

54% T; 46% P

280

RANO

7.8%

13.4

Failed in Ph 3

Omuro A (2022); Neuro Oncol.

Temozolomide chemotherapy + Radiotherapy

information not provided

60

n.a.

n.a.

12.7

Approved
(current standard of care)

Hegi ME (2005) NEJM

# For this study resection status applies to the total patient population (MGMT methylated + unmethylated)

On September 13, 2023 Calidi Biotherapeutics, Inc. (NYSE American: CLDI or "Calidi"), a clinical-stage biotechnology company developing a new generation of targeted immunotherapies, reported the completion of its business combination with First Light Acquisition Group (FLAG), a special purpose acquisition company (Press release, Calidi Biotherapeutics, SEP 13, 2023, View Source [SID1234635155]). The common stock and warrants of Calidi are expected to commence trading on the New York Stock Exchange American under the ticker symbols "CLDI" and "CLDI WS," respectively, on September 13, 2023. The stockholders of FLAG approved the transaction on August 28, 2023, following approval by Calidi shareholders. Calidi’s existing management team, including Chief Executive Officer and Chairman Allan Camaisa, will lead the combined company.

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As a result of this business combination, gross proceeds made available to Calidi Biotherapeutics, prior to the payment of transaction expenses and debt repayments, are approximately $28 million, which consists of $25 million in a private capital raise, cash proceeds of approximately $1 million from FLAG’s trust account, and approximately $2 million in PIPE and non-redemption agreements. Estimated transaction expenses and debt repayments include approximately $13 million and, in addition thereto, a $5 million working capital adjustment for expenses incurred prior to closing. The Company believes that the proceeds available to the Company from the transactions will be sufficient to fund its operations into 2025.

"We founded Calidi in 2014 with a mission to develop a new generation of targeted immunotherapies that could revolutionize the treatment of cancer," said Allan Camaisa, CEO and Chairman of the Board of Calidi Biotherapeutics. "Our team has worked diligently to build on decades of research with human stem cells and develop two novel off-the-shelf platforms designed to directly target and attack tumor cells throughout the body, and we are proud of our promising clinical results to-date. Calidi’s cutting-edge platforms NeuroNova, targeting high-grade gliomas, and SuperNova, targeting solid tumors, use allogeneic stem cells in our clinical efforts to bring a universal cancer treatment to a broad patient population who need access to new treatment options. We look forward to pushing the boundaries of cell-based virotherapies and continuing to research novel ways to eradicate cancer in this next step as a public company."

"We are proud of this collaboration with Calidi and the successful outcome of our combination, driven in part by confidence among our initial FLAG shareholders, who have made additional financial commitments to further support the company going forward," said Tom Vecchiolla, Chief Executive Officer of First Light Acquisition Group. "We are excited to see Calidi continue to grow as they transition into a public company and look forward to their clinical pursuit of new treatment options for patients everywhere in need."

Calidi is developing in the clinic first-in-class allogeneic stem cell-based delivery platforms designed to deliver a new generation of targeted immunotherapies for the treatment of cancer. These platforms include:

CLD-101 (NeuroNova): allogeneic neural stem cells loaded with an oncolytic adenovirus for the treatment of high-grade gliomas (HGG). In June 2023, the first brain tumor patient was treated at City of Hope in a multicenter, Phase 1 clinical trial evaluating CLD-101 for the treatment of HGG. The trial is assessing the safety and tolerability of administering serial doses of CLD-101 in adult patients with recurrent histologically confirmed HGG (WHO grade III or IV). Secondary endpoints will evaluate treatment efficacy, including progression-free and overall survival as well as any immune response. Interim clinical results are expected in the first half of 2024. A previously completed open-label, Phase 1, dose-escalation clinical trial in patients with newly diagnosed high-grade gliomas demonstrated that CLD-101 was well tolerated and showed promising preliminary clinical results of efficacy (Study published in the peer-reviewed journal, The Lancet Oncology, 2021).
CLD-201 (SuperNova): allogeneic adipose-derived mesenchymal stem cells (AD-MSC) loaded with tumor-selective CAL1 oncolytic vaccinia virus for the treatment of advanced metastatic solid tumors. A previously conducted physician-sponsored clinical trial using autologous adipose-derived stromal cells demonstrated that the therapeutic approach was well tolerated and showed early signs of efficacy in 24 patients with advanced solid tumors and two patients with acute myeloid leukemia (AML). (Study published in the peer-reviewed journal: Journal of Translational Medicine, 2019). In December 2022, Calidi was awarded $3.1 million from the California Institute for Regenerative Medicine (CIRM) to support the clinical development of the allogeneic off-the-shelf product CLD-201 through an Investigational New Drug (IND) application (Allogeneic platform published in the peer-reviewed journal: Cancers, 2022). Calidi has conducted the pre-IND meeting with the FDA and expects cGMP final drug product manufacturing to be completed in the first quarter of 2024. In the second half of 2024, Calidi anticipates initiating a Phase 1/2 study evaluating CLD-201 in patients with advanced metastatic solid tumors, including triple-negative breast cancer, unresectable melanoma, and squamous cell head and neck carcinoma.
Proceeds from the business combination are also expected to support the expansion of Calidi’s stem cell-based delivery platforms into additional indications.
Transaction Summary

Calidi Biotherapeutics, a private biotechnology company, and First Light Acquisition Group, a special purpose acquisition company, entered into a definitive business combination agreement on January 9, 2023.

As a result of this business combination, gross proceeds made available to Calidi Biotherapeutics, prior to the payment of transaction expenses and debt repayments, are approximately $28 million, which consists of $25 million in a private capital raise, cash proceeds of approximately $1 million from FLAG’s trust account, and approximately $2 million in PIPE and non-redemption agreements. Estimated transaction expenses and debt repayments include approximately $13 million and, in addition thereto, a $5 million working capital adjustment for expenses incurred prior to closing. In addition, Calidi has entered into a forward purchase agreement with a consortium including Meteora Capital LLC, Great Point Capital LLC, and Funicular Funds, LP for up to $10 million, and Calidi intends to enter into a purchase agreement for up to $50 million with Lincoln Park Capital Fund, LLC, subject to an effective registration statement to be filed with the Securities and Exchange Commission. Both of these opportunities have the potential to add cash to the balance sheet in the future. The Company believes that the proceeds available to the Company from the transactions will be sufficient to fund its operations into 2025.

The description of the business combination contained herein is only a high-level summary and is qualified in its entirety by reference to the underlying documents filed with the U.S. Securities and Exchange Commission. A more detailed description of the terms of the transaction has been provided in a registration statement on Form S-4 filed with the U.S. Securities and Exchange Commission by First Light Acquisition Group.

Advisors

Brookline Capital Markets, a Division of Arcadia Securities, LLC, acted as placement agent for the private capital raise, a Calidi Series B Preferred Stock Financing, and as an advisor to First Light Acquisition Group, Inc. Lewis Brisbois Bisgaard & Smith LLP acted as legal counsel to Calidi. Weil, Gotshal & Manges LLP acted as legal counsel to FLAG.