Calidi Biotherapeutics and First Light Acquisition Group (FLAG) Announce Merger Agreement to Create a Publicly Listed, Clinical-Stage Biotechnology Company Utilizing Stem Cell-Based Platforms to Revolutionize Oncolytic Virotherapies

On January 09, 2023 Calidi Biotherapeutics, Inc. ("Calidi" or the "Company"), a clinical-stage biotechnology company that is pioneering the development of allogeneic cell-based delivery of oncolytic viruses, and First Light Acquisition Group ("FLAG") (NYSE American: FLAG), a special purpose acquisition company organized to acquire or merge with one or more businesses, reported they have entered into a definitive merger agreement to create a public company focused on developing oncolytic viral therapies with stem cell-based delivery platforms to treat a wide range of cancers with significant unmet needs (Press release, Calidi Biotherapeutics, JAN 9, 2023, View Source [SID1234626041]). Upon closing of the transaction, anticipated to occur in the second quarter of 2023, the combined company will be named Calidi Biotherapeutics, Inc. and led by Allan Camaisa, CEO and Chairman of the Board. In addition, the combined company’s common stock intends to list on the NYSE American under the ticker "CLDI."

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Calidi Biotherapeutics is revolutionizing the clinical development of first-in-class allogenic stem cell-based delivery platforms to protect, deliver, and potentiate oncolytic viruses for the treatment of cancer. Calidi’s technology directly addresses a critical obstacle in traditional oncolytic virotherapy, overcoming the oncolytic virus inactivation by a patient’s immune system through an allogeneic stem cell delivery mechanism to successfully target a wide range of cancers, including high-grade gliomas (HGG) and solid tumors. Calidi’s pipeline includes two "off-the-shelf" clinical programs, NeuroNova (CLD-101) and SuperNova (CLD-201), which utilize allogeneic stem cell technologies loaded with either vaccinia virus or adenovirus, being developed in partnership with leading research institutions.

"We are excited to partner with FLAG which we believe will accelerate our ability to bring life-changing therapies to patients, pairing our first-in-class, allogeneic stem cell-based technology with strategic partnering opportunities, to advance our goal of revolutionizing cancer treatment," said Allan Camaisa, CEO and Chairman of the Board of Calidi Biotherapeutics. "This business combination positions us well as we build upon the momentum generated to date from our NeuroNova and SuperNova platforms, which have the potential to overcome the limitations of first-generation oncolytic virus therapies. Furthermore, the merger will allow us to leverage FLAG’s comprehensive network in both the private and public sectors, capital markets and operational experience, and successful track record addressing missions of U.S. national and global importance. We believe recent legislative progress supporting federal funding for new cancer treatments provides an immediate opportunity to showcase our combined synergy, where our strong backgrounds align with a shared goal of bringing novel therapeutic options to cancer patients in need."

"We are very pleased to announce this merger with Calidi Biotherapeutics as their differentiated technology shows potential to enable improved quality of care, extend survival, and lower cost of treatment in a market with a high unmet need," said Tom Vecchiolla, CEO of FLAG. "Our goal is to invest in people and technologies that address the most important priorities and to deliver results with national and global effect. We believe that Calidi’s innovative technology offers a differentiated immuno-oncology solution with a proprietary allogeneic stem cell-based universal delivery system that harnesses the potential of oncolytic viruses to address therapeutic needs in hard-to-treat cancers."

The transaction includes gross proceeds of up to $42 million in trust with FLAG (assuming no redemptions by existing FLAG shareholders). The parties will attempt to arrange a PIPE Investment from institutional investors of up to $40 million.

Net proceeds from the transaction are expected to provide Calidi with capital into the first half of 2025 to advance its pipeline of therapeutic candidates through multiple clinical milestones, including:

NeuroNova (CLD-101): allogeneic neural stem cells loaded with an oncolytic adenovirus for the treatment of HGG. A 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.In August 2022, City of Hope received U.S. Food and Drug Administration (FDA) authorization to proceed with another Phase 1 physician-sponsored clinical trial that will use Calidi’s CLD-101 platform in patients with recurrent HGG. The trial will assess 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.
SuperNova (CLD-201): 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 CLD-201 was well tolerated and showed early signs of efficacy in 24 patients with advanced solid tumors and two patients with acute myeloid leukemia (AML).In December 2022, Calidi was awarded $3.1 million from the California Institute for Regenerative Medicine (CIRM) to support the clinical development of CLD-201 through an Investigational New Drug (IND) application, which the company anticipates submitting in the second half of 2023. Additionally, Calidi expects interim results from a CLD-201 Phase 1 trial in the first half of 2024.
Proceeds from the transaction are also expected to support expansion of Calidi’s stem cell-based delivery platforms into additional indications
Key Transaction Terms
Upon closing of the business combination (the "Business Combination"), shareholders of Calidi (assuming the conversion of all derivative securities other than unvested options) will be entitled to receive 25,000,000 shares of FLAG common stock, subject to adjustments and after the closing, shareholders of Calidi may be entitled up to 18,000,000 additional shares of FLAG common stock (the "Escalation Shares") during a five year period with incremental releases of 4,500,000 shares if the trading price of FLAG common stock is $12, $14, $16 and $18 for a period for any 20 days within any 30 consecutive day trading period. Furthermore, holders of FLAG Class A common stock who do not redeem their shares may be entitled to their pro rata portion of up to an additional 2,000,000 shares of FLAG common stock during a five-year period with incremental releases of up to 500,000 shares if the trading price of FLAG common stock is $12, $14, $16 and $18 for a period for any 20 days within any 30 consecutive day trading period. Assuming no redemptions of shares of FLAG by its public shareholders and a possible PIPE Investment from institutional investors of up to $40 million, Calidi expects to have cash and cash equivalents, prior to transaction expenses, of up to $82 million and an anticipated pro forma enterprise valuation of approximately $335 million.

The boards of directors of Calidi and FLAG unanimously approved the proposed transaction, which is anticipated to close in the second quarter of 2023. The closing of the transaction is subject to the approval of FLAG shareholders, regulatory approval, a minimum cash condition of $15 million, after the payment of transaction expenses, and the satisfaction or waiver of certain other customary closing conditions.

A Current Report on Form 8-K, filed by FLAG with the Securities and Exchange Commission (SEC), will provide additional information about the proposed business combination and will be available on the SEC’s website at www.sec.gov. In addition, FLAG intends to file a registration statement on Form S-4 with the SEC, including a proxy statement/prospectus, and will file other documents regarding the proposed transaction with the SEC.

Advisors
Lewis Brisbois Bisgaard & Smith LLP acted as legal counsel to Calidi. Weil, Gotshal & Manges LLP acted as legal counsel to FLAG.

C4 Therapeutics Announces 2023 Strategic Priorities to Advance Portfolio of Targeted Protein Degradation Medicines

On January 09, 2023 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported 2023 strategic priorities to advance its portfolio of targeted protein degradation medicines (Press release, C4 Therapeutics, JAN 9, 2023, View Source [SID1234626040]).

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"In 2022, C4T progressed multiple oncology programs by initiating two clinical trials, sharing early clinical data from our lead program, and demonstrating the capabilities of our TORPEDO platform to develop both MonoDAC and BiDAC degraders," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "Based on these achievements, 2023 will be an important year with clinical data expected from our two lead programs, CFT7455 and CFT8634. We are well-resourced to execute against our strategic priorities to advance four distinct oncology programs in the clinic by the end of 2023 and deliver on the promise of targeted protein degradation science for the benefit of patients."

RECENT ACHIEVEMENTS AND ANTICIPATED 2023 OBJECTIVES

CFT7455: CFT7455 is an oral degrader of IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL).

Recent Achievements:

Progression of the ongoing Phase 1/2 clinical trial with the opening of Arm B2, evaluating CFT7455 in combination with dexamethasone for the treatment of MM.
2023 Objectives:

Continue dose escalation in Arms B1, B2 and C of the Phase 1/2 trial, evaluating CFT7455 as a single agent in MM, in combination with dexamethasone in MM, and as a single agent in NHL, respectively.
Present Phase 1 dose escalation data from the ongoing Phase 1/2 trial of CFT7455 in MM in the second half of 2023.
CFT8634: CFT8634 is an oral degrader of BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.

Recent Achievements:

Pharmacokinetic (PK) and pharmacodynamic (PD) data from the initial escalation cohorts of the ongoing CFT8634 Phase 1/2 trial demonstrate dose proportional exposure, strong oral bioavailability and deep BRD9 degradation.
2023 Objectives:

Continue dose escalation of the CFT8634 Phase 1/2 trial in synovial sarcoma and SMARCB1-null solid tumors.
Present Phase 1 dose escalation data from the ongoing CFT8634 Phase 1/2 trial in the second half of 2023.
CFT1946: CFT1946 is an oral degrader targeting BRAF-V600 mutations for the treatment of solid tumors including non-small cell lung cancer (NSCLC), colorectal cancer and melanoma.

Recent Achievements:

Initiated the Phase 1/2 trial of CFT1946 for the treatment of BRAF-V600 mutant cancers including NSCLC, colorectal cancer and melanoma.
2023 Objectives:

Advance the dose escalation portion of the CFT1946 Phase 1/2 trial in BRAF-V600 mutant solid tumors.
Present new preclinical data on the discovery and characterization of CFT1946 as a potent, selective, and orally bioavailable degrader for the treatment of BRAF-V600-driven cancers at a medical meeting in the first half of 2023.
CFT8919: CFT8919 is a potent and selective oral degrader of EGFR L858R for the treatment of NSCLC.

Recent Achievements:

Completed investigational new drug (IND) enabling activities for CFT8919.
2023 Objectives:

Submit an IND application for CFT8919 for the treatment of NSCLC in the first half of 2023.
CASH GUIDANCE

The company expects that its cash, cash equivalents and marketable securities as of September 30, 2022, together with anticipated collaboration expense reimbursements, but excluding any collaboration option or milestone payments, will enable the company to fund its operating plan to the end of 2024.

JP MORGAN PRESENTATION

C4T will present at the 41st Annual J.P. Morgan Healthcare Conference today, January 9, at 10:30 am PST (1:30 pm EST). A live webcast will be available under "Events & Presentations" in the Investors section of the company’s website at www.c4therapeutics.com.

bluebird bio Provides Update on Commercial Launch Progress, Program Milestones and 2023 Financial Outlook Ahead of Company Presentation at 41st Annual J.P. Morgan Healthcare Conference

On January 09, 2023 bluebird bio, Inc. (Nasdaq: BLUE) (the Company) reported updates to be presented at the 41st Annual J.P. Morgan Healthcare conference including commercial launch progress, 2023 program milestones and financial outlook. CEO Andrew Obenshain is scheduled to speak on Thursday, January 12 at 7:30 a.m. PT (Press release, bluebird bio, JAN 9, 2023, View Source [SID1234626037]).

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"In 2022, bluebird bio emerged as a commercial stage gene therapy company, with a validated lentiviral vector platform built on more than a decade of scientific leadership," said Andrew Obenshain, chief executive officer, bluebird bio. "In a dynamic and challenging environment, bluebird has hit all its operational milestones, including nearly simultaneous launches of two first-in-class gene therapies, ZYNTEGLO and SKYSONA. We have strengthened our financial position and generated considerable momentum as we prepare for the opportunity ahead: bringing lovo-cel gene therapy to individuals living with sickle cell disease and their families."

Highlights from the Company’s Update Include:

Significant Momentum and Early Signs of Uptake for ZYNTEGLO (betibeglogene autotemcel) Commercial Launch

Apheresis for first commercial ZYNTEGLO patient completed; Company entered 2023 with multiple patient cell collections scheduled. First revenue anticipated for Q1 2023 as previously guided.
Early indicators continue to demonstrate significant patient demand for ZYNTEGLO. Approximately 40 patients have initiated benefits verification, with a significant proportion progressing to prior authorization approval across both Medicaid and commercial payer segments and zero ultimate denials to date.
bluebird’s qualified treatment center (QTC) network is scaling as planned, with 10 activated centers to date. More than 15 additional QTCs are in the on-boarding or master service agreement negotiation stage, aligned with the Company’s expectation to scale to 40-50 centers by the end of 2023.
Outcomes-based agreements are in place with 3 of the largest pharmacy benefit managers in the US, representing dozens of downstream national and regional plans. To date, approximately 190 million US lives are covered by a favorable coverage policy for ZYNTEGLO.
During ZYNTEGLO’s 2023 launch year, the Company expects to assess key metrics over time as launch progresses such as number of patient starts and percent of lives covered and does not expect to provide ZYNTEGLO revenue projections this year.
SKYSONA (elivaldogene autotemcel) Commercial Launch on Track

Cell collection for first patient to be treated commercially with SKYSONA scheduled for January 2023.
Clear path to lovotibeglogene autotemcel (lovo-cel) BLA submission in Q1 2023

bluebird completed vector and drug product analytical comparability studies in the 4th quarter of 2022, as previously guided. With this progress, bluebird remains on track to submit its biologics license application (BLA) to the U.S. Food and Drug Administration this quarter.
2023 Financial Outlook

The Company’s preliminary unaudited cash and cash equivalents and marketable securities balance was approximately $182 million, excluding restricted cash of approximately $45 million, as of December 31, 2022. As bluebird bio launches two first-in-class gene therapies and readies its third investigational gene therapy for SCD for the commercial setting, full-year 2023 cash burn is expected to be in the range of $270-$300 million. bluebird expects its cash, cash equivalents, restricted cash and marketable securities, including the proceeds from the sale of its second priority review voucher (PRV) for $95 million, will be sufficient to meet bluebird’s planned operating expenses and capital expenditure requirements into the first quarter of 2024.

Presentation at the 2023 J.P. Morgan Healthcare Conference

Andrew Obenshain, chief executive officer, bluebird bio, will present a corporate update on Thursday, January 12, at 7:30 a.m. PT. A live webcast of the presentation will be available on the "Events & Presentations" page within the Investors & Media section of the bluebird bio website at View Source A replay of the webcast will be available on the bluebird bio website for 30 days following the event.

Corporate Overview

On January 9, 2023 Century therapeutics presented its corporate overview (Presentation, Century Therapeutics, JAN 9, 2023, View Source [SID1234626044]).

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Biomea Fusion to Present at 41st Annual J.P. Morgan Healthcare Conference and Highlight 2023 Corporate Milestones

On January 09, 2023 Biomea Fusion, Inc. (Nasdaq: BMEA), a clinical-stage biopharmaceutical company dedicated to discovering and developing novel covalent small molecules to treat and improve the lives of patients with genetically defined cancers and metabolic diseases, reported that Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board, will present recent progress and 2023 corporate milestones at the 41st Annual J.P. Morgan Healthcare Conference on Wednesday, January 11, 2023 from 11:15 – 11:55 am ET, and that Biomea management will hold 1×1 meetings during the conference January 9 – 11 (Press release, Biomea Fusion, JAN 9, 2023, View Source [SID1234626036]).

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A live webcast of the presentation will be available on the Investors & Media page of Biomea’s website at: View Source

"2022 was a year of strong execution and fundamental infrastructure build as we transitioned to a clinical-stage company and expanded our pipeline. We enter 2023 with three clinical trials studying BMF-219 across 8 cancer indications covering both blood cancers and solid tumors as well as in Type 2 diabetes, the 7th leading cause of death in the United States," stated Thomas Butler, Biomea Fusion’s Chief Executive Officer and Chairman of the Board. "We anticipate advancing BMF-500 into the clinic during the first half of 2023, subsequent to FDA clearance of an IND, which will increase our clinical pipeline to 4 clinical trials covering 10 indications. COVALENT-111, our Phase I/II study in Type 2 diabetes is now due to report initial safety and efficacy from the first two cohorts of the Phase II portion by the end of Q1."

Mr. Butler further commented, "we continue to activate sites and enroll patients in our Phase I/Ib (COVALENT-101) study of BMF-219 in patients with several liquid tumor types, and plan to report initial clinical data from this study in the first half of 2023. In addition, we anticipate initiating dosing imminently in our Phase I/Ib (COVALENT-102) study of BMF-219 in patients with KRAS-mutated solid tumors. In 2023, we will continue the patient-centric urgency and disciplined execution that are now well-established hallmarks of Team Fusion."

RECENT & ANTICIPATED MILESTONES

ONCOLOGY

COVALENT-101 (BMF-219)
Presented robust anti-tumor activity of covalent menin small molecule inhibitor, BMF-219, as a single agent and mechanistic evidence for novel inhibition of the menin protein in preclinical models of diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), and chronic lymphocytic leukemia (CLL). BMF-219 displayed single agent potency, surpassing greater than 90% cell killing at clinically relevant exposures in DLBCL, MM and CLL cell lines and patient-derived samples.
BMF-219 is the first investigational menin inhibitor in clinical development to show potential as a therapeutic agent in hematologic malignancies outside of MLLr and NPM1 mutated acute myeloid leukemia/acute lymphoblastic leukemia (AML/ALL) patients, specifically in subsets of DLBCL, MM and CLL patients.
Biomea continued site activation and patient enrollment for the dosing of BMF-219 across four liquid tumor cohorts in the COVALENT-101 study, including patients with AML/ALL, DLBCL, MM and CLL.
Next Anticipated Milestone:
On track to present initial clinical data of AML/ALL patients (including those with MLL rearrangement and NPM1 mutation) dosed in the COVALENT-101 study in the first half of 2023.
COVALENT-102 (BMF-219)
Presented strong and highly specific pan-KRAS anti-cancer activity of BMF-219 as a single agent across KRAS G12C, G12D, G12V and G13D mutant cell lines including in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and the most prevalent type of pancreatic cancer, PDAC.
BMF-219 is the first investigational menin inhibitor in development to enter clinical trials for the treatment of solid tumors. A targeted pan-KRAS inhibitor could have the potential to treat 25-35% of NSCLC, 35-45% of CRC, and approximately 90% of PDAC patients.
Biomea received FDA clearance of its IND in the fourth quarter of 2022 and has since initiated a Phase I/Ib clinical trial of BMF-219 as a monotherapy in patients who have unresectable, locally advanced, or metastatic NSCLC, CRC or PDAC with an activating KRAS mutation.
Next Anticipated Milestone:
On track to dose first patient in COVALENT-102 study in January 2023.
COVALENT-103 (BMF-500)
Presented data showing multi-fold higher potency and increased cytotoxicity of Biomea’s covalent FLT3 small-molecule inhibitor BMF-500 compared to the commercially available reversible, non-covalent FLT3 inhibitor gilteritinib, and complete, sustained tumor regression in mouse models of FLT3-ITD AML with maintenance of effect after cessation of therapy.
Next Anticipated Milestone:
On track to file IND for BMF-500 in the first half of 2023 to initiate COVALENT-103 study of the covalent FLT3 inhibitor in patients with acute leukemia.
DIABETES

COVALENT-111 (BMF-219)
Presented preclinical data highlighting the ability of BMF-219 in a Type 2 diabetes rat model to restore normal HOMA-B, a measure of pancreatic beta cell function, following only 4-weeks of treatment and to significantly lower HbA1c compared to active control, liraglutide, -3.5% vs -1.7%, respectively.
BMF-219 is the first investigational menin inhibitor in development to enter clinical trials for the improvement of glycemic control and insulin sensitivity in Type 2 diabetes patients.
Biomea completed the healthy volunteer portion of the Phase I/II COVALENT-111 study of BMF-219 in Canada. BMF-219 was well tolerated with an encouraging pharmacokinetic and pharmacodynamic profile in healthy volunteers and with no safety signals detected.
Biomea received FDA clearance in December 2022 to expand the Phase II portion of COVALENT-111 to sites in the U.S. and in January 2023 announced dosing of the first U.S. patient with Type 2 diabetes. The company continues to enroll Type 2 diabetes patients in the Phase II portion of the study in Canada as well.
Next Anticipated Milestones:
On track to present initial clinical data from the first two cohorts of the Phase II portion of the study by the end of Q1 2023, and to present details of the healthy volunteer (Phase I) portion of the study at a scientific medical meeting in 2023.
FUSION SYSTEM DISCOVERY PLATFORM

Developed two covalently binding small molecules (BMF-219 and BMF-500), each within 18 months from target identification to IND candidate, leveraging the proprietary FUSION System Discovery Platform and showing excellent preclinical profiles.
Next Anticipated Milestone:
On track to announce a third development candidate from the FUSION platform in the first half of 2023.